Lyme-Literate Top Expert Researcher Offers Vast Numbers of Antivirals: Many Synthetic Virus Medications and Natural Remedies

Novel broad-spectrum candidates rather than standard drugs, #61–98 deserve a mention….

Especially quercetin, baicalein/baicalin, EGCG, curcumin, resveratrol, andrographolide, glycyrrhizin, berberine, lactoferrin, sulforaphane, fungal polysaccharides and β-glucans.

Established antiviral = reproducible antiviral benefit has been demonstrated in humans, or the agent has a regulatory indication based on an accepted pathway such as the FDA Animal Rule.

Clinical/limited = human data exist, but the indication, geography, resistance, toxicity, or quality of evidence limits routine use.

Experimental/preclinical = antiviral effects are mainly from cells, biochemical systems, mice, hamsters, ferrets, rabbits, nonhuman primates, or other animal models; this does not establish that it treats human infection.

Match the references exactly as requested: Agent 56 → Endnote 56; Agent 100 → Endnote 100.

100 Antivirals: Established vs. Experimental

#	Agent	Evidence category	What makes it established or experimental?	Evidence base
1	Acyclovir	ESTABLISHED	Multiple controlled human trials demonstrate clinical HSV efficacy.	Human [1]
2	Valacyclovir	ESTABLISHED	Acyclovir prodrug with established human efficacy for HSV/VZV.	Human [2]
3	Famciclovir	ESTABLISHED	Controlled human herpes-zoster trials.	Human [3]
4	Penciclovir	ESTABLISHED—topical	Controlled human herpes-labialis studies.	Human [4]
5	Ganciclovir	ESTABLISHED	Clinical efficacy against CMV, especially in immunocompromised patients.	Human [5]
6	Valganciclovir	ESTABLISHED	Oral ganciclovir prodrug supported by controlled human CMV studies.	Human [6]
7	Foscarnet	ESTABLISHED	Used clinically for resistant CMV/HSV; efficacy established despite substantial toxicity.	Human [7]
8	Cidofovir	ESTABLISHED	Controlled clinical evidence for CMV retinitis; broad DNA-virus activity experimentally.	Human [8]
9	Letermovir	ESTABLISHED	Large randomized human CMV-prevention trial.	Human [9]
10	Maribavir	ESTABLISHED	Randomized human studies in refractory/resistant CMV.	Human [10]
11	Trifluridine	ESTABLISHED—ophthalmic	Established topical ophthalmic HSV therapy.	Human [11]
12	Brivudine	ESTABLISHED/REGION-SPECIFIC	Human efficacy against herpes zoster; marketed in selected countries, not universally.	Human [12]
13	Docosanol	ESTABLISHED—topical	Placebo-controlled human herpes-labialis trial.	Human [13]
14	Oseltamivir	ESTABLISHED	Randomized human influenza trials and extensive clinical experience.	Human [14]
15	Zanamivir	ESTABLISHED	Randomized human influenza trials.	Human [15]
16	Peramivir	ESTABLISHED	Human clinical influenza studies; IV neuraminidase inhibitor.	Human [16]
17	Baloxavir marboxil	ESTABLISHED	Large controlled human influenza trials.	Human [17]
18	Laninamivir octanoate	ESTABLISHED/REGION-SPECIFIC	Human influenza trials; principally used in Japan.	Human [18]
19	Favipiravir	LIMITED/REGION-SPECIFIC	Strong antiviral pharmacology and clinical influenza use in selected settings, but not a broadly approved general-purpose antiviral.	Human + mammalian/preclinical [19]
20	Ribavirin	ESTABLISHED FOR SELECT INDICATIONS	Human clinical utility exists, but efficacy and toxicity are highly disease-specific.	Human [20]
21	Nirmatrelvir/ritonavir	ESTABLISHED	Large randomized clinical COVID-19 trial demonstrated reduced progression in high-risk patients.	Human [21]
22	Remdesivir	ESTABLISHED	Randomized human COVID-19 trials; originally supported by broad RNA-virus animal work.	Human + mammalian [22]
23	Molnupiravir	ESTABLISHED BUT SECOND-LINE/RESTRICTED	Human randomized data exist, although clinical benefit is more modest and indications are restricted.	Human [23]
24	Tenofovir disoproxil fumarate	ESTABLISHED	Major human HBV/HIV antiviral.	Human [24]
25	Tenofovir alafenamide	ESTABLISHED	Controlled human HBV/HIV evidence.	Human [25]
26	Entecavir	ESTABLISHED	Large controlled human chronic-HBV studies.	Human [26]
27	Lamivudine	ESTABLISHED	Human HBV/HIV antiviral, although HBV resistance limits long-term monotherapy.	Human [27]
28	Adefovir dipivoxil	ESTABLISHED BUT LARGELY SUPERSEDED	Human HBV efficacy established; newer drugs generally preferred.	Human [28]
29	Telbivudine	ESTABLISHED BUT LARGELY SUPERSEDED	Controlled HBV efficacy but substantial resistance limitations.	Human [29]
30	Peginterferon alfa	ESTABLISHED	Human antiviral/immunomodulatory treatment for HBV and historically HCV.	Human [30]
31	Sofosbuvir	ESTABLISHED	Transformative human HCV NS5B inhibitor with very high cure rates in combinations.	Human [31]
32	Velpatasvir	ESTABLISHED	Human pangenotypic HCV NS5A inhibitor.	Human [32]
33	Glecaprevir	ESTABLISHED	Human HCV NS3/4A inhibitor used with pibrentasvir.	Human [33]
34	Pibrentasvir	ESTABLISHED	Human pangenotypic HCV NS5A inhibitor.	Human [34]
35	Ledipasvir	ESTABLISHED	Human HCV NS5A inhibitor; highly effective with sofosbuvir.	Human [35]
36	Voxilaprevir	ESTABLISHED	Human HCV protease inhibitor used principally in salvage combinations.	Human [36]
37	Elbasvir	ESTABLISHED	Controlled human HCV studies.	Human [37]
38	Grazoprevir	ESTABLISHED	Controlled human HCV studies with elbasvir.	Human [38]
39	Dolutegravir	ESTABLISHED	Major first-line HIV integrase inhibitor supported by randomized human trials.	Human [39]
40	Bictegravir	ESTABLISHED	Randomized human HIV trials.	Human [40]
41	Raltegravir	ESTABLISHED	First-in-class HIV integrase inhibitor with extensive human trial evidence.	Human [41]
42	Cabotegravir	ESTABLISHED	Long-acting HIV integrase inhibitor supported by human treatment and prevention trials.	Human [42]
43	Darunavir	ESTABLISHED	Human HIV protease inhibitor with high resistance barrier.	Human [43]
44	Atazanavir	ESTABLISHED	Established human HIV protease inhibitor.	Human [44]
45	Maraviroc	ESTABLISHED	Human CCR5-targeted HIV-entry inhibitor.	Human [45]
46	Enfuvirtide	ESTABLISHED	Human gp41 fusion inhibitor, particularly historically important for resistant HIV.	Human [46]
47	Fostemsavir	ESTABLISHED	Human attachment inhibitor for multidrug-resistant HIV.	Human [47]
48	Ibalizumab	ESTABLISHED	Human anti-CD4 monoclonal antibody for multidrug-resistant HIV.	Human [48]
49	Lenacapavir	ESTABLISHED	Long-acting HIV capsid inhibitor with human efficacy studies.	Human [49]
50	Doravirine	ESTABLISHED	Human NNRTI supported by randomized trials.	Human [50]
51	Efavirenz	ESTABLISHED	Extensive randomized human HIV evidence.	Human [51]
52	Emtricitabine	ESTABLISHED	Major NRTI incorporated into numerous evidence-based HIV regimens.	Human [52]
53	Zidovudine	ESTABLISHED/HISTORICALLY IMPORTANT	First major antiretroviral shown to benefit humans with advanced HIV disease.	Human [53]
54	Tecovirimat	ESTABLISHED FOR SMALLPOX VIA ANIMAL RULE; NOT PROVEN GENERALLY FOR MPOX	Unusual case: efficacy underlying smallpox approval came from rabbits and nonhuman primates plus human safety/PK. A 2026 human clade-II-mpox trial did not establish a general mpox-treatment effect.	Mammalian + human safety [54]
55	Brincidofovir	ESTABLISHED FOR SMALLPOX VIA SPECIAL REGULATORY PATHWAY / LIMITED HUMAN VIRAL EFFICACY DATA	Broad DNA-virus activity; smallpox efficacy cannot ethically be tested directly in humans.	Mammalian + human safety [55]
56	Palivizumab	ESTABLISHED—PREVENTION, NOT TREATMENT	Randomized human infant studies showed reduced RSV hospitalization.	Human [56]
57	Nirsevimab	ESTABLISHED—PREVENTION, NOT TREATMENT	Long-acting anti-RSV monoclonal antibody supported by large infant trials.	Human [57]
58	Interferon alfa	ESTABLISHED FOR SELECT VIRAL DISEASES	Genuine host-directed antiviral but largely superseded for several indications.	Human [58]
59	Peginterferon lambda	CLINICAL/INVESTIGATIONAL DEPENDING INDICATION	Human antiviral trials exist, including COVID-19, but it is not a universal licensed antiviral.	Human [59]
60	Amantadine	HISTORICALLY ESTABLISHED; NO LONGER ROUTINELY RECOMMENDED FOR INFLUENZA	Influenza-A M2 inhibitor rendered clinically unhelpful by widespread resistance.	Human [60]
61	Quercetin	EXPERIMENTAL ANTIVIRAL	Broad cell and animal antiviral findings; insufficient disease-specific human evidence to classify as an established antiviral drug.	In-vitro + mammalian/limited human [61]
62	Baicalein	EXPERIMENTAL	Antiviral activity across multiple viruses in vitro and animal models; clinical evidence insufficient.	In-vitro + mammalian [62]
63	Baicalin	EXPERIMENTAL	Mechanistic and mammalian antiviral evidence, but insufficient standardized human trials.	In-vitro + mammalian/limited clinical [63]
64	EGCG	EXPERIMENTAL	Inhibits several stages of numerous viral life cycles experimentally; clinical therapeutic efficacy remains unestablished.	In-vitro + some mammalian [64]
65	Curcumin	EXPERIMENTAL	Activity reported against many viruses, mostly in vitro/preclinical; bioavailability is a translational problem.	In-vitro + mammalian [65]
66	Resveratrol	EXPERIMENTAL	Antiviral activity demonstrated for multiple human and animal viruses, including some in-vivo models; no established antiviral indication.	In-vitro + mammalian [66]
67	Andrographolide	EXPERIMENTAL	Diverse antiviral mechanisms reported, but therapeutic human proof remains inadequate.	In-vitro + mammalian [67]
68	Glycyrrhizin	EXPERIMENTAL/LIMITED CLINICAL HISTORY	Antiviral activity in laboratory and some clinical contexts but not an established broad-spectrum antiviral drug; toxicity matters.	In-vitro + mammalian + limited human [68]
69	Berberine	EXPERIMENTAL	Broad laboratory antiviral effects; insufficient randomized disease-specific human evidence.	In-vitro + mammalian [69]
70	Apigenin	EXPERIMENTAL	Mechanistic and cellular antiviral findings; limited in-vivo translation.	In-vitro + some mammalian [70]
71	Luteolin	EXPERIMENTAL	Has experimentally inhibited viruses including dengue; not established clinically.	In-vitro/preclinical [71]
72	Kaempferol	EXPERIMENTAL	Broad flavonoid antiviral findings are predominantly preclinical.	In-vitro + animal studies [72]
73	Myricetin	EXPERIMENTAL	Viral enzyme/entry/replication effects reported experimentally without therapeutic human proof.	Preclinical [73]
74	Hesperidin	EXPERIMENTAL	Mostly molecular, cellular and animal evidence rather than definitive human antiviral treatment trials.	Preclinical [74]
75	Naringenin	EXPERIMENTAL	Antiviral and host-metabolic effects in HCV, dengue and other experimental systems.	In-vitro + mammalian [75]
76	Genistein	EXPERIMENTAL	Host-signaling effects can alter viral replication experimentally; not a licensed antiviral.	In-vitro + mammalian [76]
77	Silymarin/silibinin	EXPERIMENTAL/CLINICALLY STUDIED	HCV antiviral effects were investigated in humans, particularly IV silibinin, but modern DAAs superseded this approach.	Human + preclinical [77]
78	Epicatechin gallate	EXPERIMENTAL	Tea catechin with antiviral laboratory activity; little direct therapeutic human evidence.	Preclinical [78]
79	Theaflavins	EXPERIMENTAL	Viral enzyme/entry inhibition primarily from laboratory studies.	Preclinical [79]
80	Allicin	EXPERIMENTAL	Garlic organosulfur compound with mechanistic antiviral effects, but instability/bioavailability impede translation.	In-vitro + mammalian [80]
81	Ajoene	EXPERIMENTAL	Garlic-derived organosulfur compound; antiviral evidence remains predominantly laboratory/preclinical.	Preclinical [81]
82	Elderberry extract	CLINICALLY STUDIED BUT NOT ESTABLISHED ANTIVIRAL	Small respiratory-illness trials exist, but heterogeneous extracts and limited trial sizes preclude equating it with licensed influenza antivirals.	Human [82]
83	Echinacea extracts	CLINICALLY STUDIED BUT NOT ESTABLISHED	Numerous human common-cold studies are heterogeneous and product dependent; evidence is inconsistent.	Human [83]
84	Lactoferrin	EXPERIMENTAL	Broad entry/attachment effects against multiple viruses, mainly from cellular and preclinical research.	In-vitro + mammalian/limited human [84]
85	Glycerol monolaurate / monolaurin	EXPERIMENTAL	Can inactivate lipid-enveloped viruses under experimental conditions; this does not establish systemic human antiviral therapy.	Laboratory [85]
86	Lauric acid	EXPERIMENTAL	Membrane-disrupting activity against enveloped viruses is primarily experimental.	Laboratory [86]
87	Melatonin	HOST-MODULATING/EXPERIMENTAL AS ANTIVIRAL	More appropriately considered immunomodulatory/anti-inflammatory than a direct virus-specific antiviral.	Mammalian + human adjunct studies [87]
88	Sulforaphane	EXPERIMENTAL	NRF2-related host-defense and antiviral effects are biologically plausible and experimentally supported, but no established antiviral indication exists.	In-vitro + mammalian [88]
89	Propolis extracts	EXPERIMENTAL	Direct anti-HSV effects are readily demonstrable in vitro, but extracts vary chemically and systemic clinical evidence is inadequate.	In-vitro + limited human topical evidence [89]
90	Caffeic acid phenethyl ester (CAPE)	EXPERIMENTAL	HCV and other antiviral effects reported in cell-based studies; no established clinical antiviral application.	In-vitro [90]
91	Eugenol	EXPERIMENTAL	Antiviral and host-modulatory mechanisms described in experimental literature; rigorous human antiviral trials remain necessary.	In-vitro + mammalian [91]
92	Carvacrol	EXPERIMENTAL	Membrane-active phenolic with antiviral effects particularly against enveloped viruses; clinical efficacy unproven.	In-vitro [92]
93	Thymol	EXPERIMENTAL	Antiviral activity exists experimentally, but it is not an established systemic antiviral.	In-vitro [93]
94	Cinnamaldehyde	EXPERIMENTAL	Laboratory antiviral activity and host effects do not yet translate into an established human treatment.	In-vitro/preclinical [94]
95	β-Glucans	IMMUNOMODULATORY/EXPERIMENTAL	These are principally innate-immune modulators rather than direct antiviral drugs.	Mammalian + limited human [95]
96	Ganoderma lucidum compounds	EXPERIMENTAL	Triterpenoids/polysaccharides show antiviral properties in vitro and in vivo, but purified standardized human antiviral trials are lacking.	In-vitro + mammalian [96]
97	Cordyceps/cordycepin compounds	EXPERIMENTAL	Antiviral and immunomodulatory activity in experimental systems; no established human antiviral indication.	In-vitro + mammalian [97]
98	Sulfated polysaccharides	EXPERIMENTAL PLATFORM	Particularly interesting viral-entry inhibitors, but chemical heterogeneity, molecular size, absorption and anticoagulant effects complicate systemic development.	In-vitro + mammalian/limited clinical [98]
99	Zinc	NUTRIENT/HOST-DIRECTED; NOT A GENERAL ANTIVIRAL DRUG	Essential for antiviral immunity and can directly inhibit viruses experimentally, but treatment efficacy varies strongly by virus, formulation and deficiency status.	Human + mammalian + in-vitro [99]
100	Selenium	NUTRIENT/HOST-DIRECTED; NOT A DIRECT ANTIVIRAL DRUG	Selenium status affects mammalian antiviral immunity and oxidative defense; supplementation should not be equated with virus-specific therapy.	Human + mammalian [100]

The major conceptual separation is therefore approximately #1–60 = predominantly clinically validated/licensed, historical, or limited clinical antiviral agents, whereas #61–100 = largely experimental natural compounds, host-directed substances, nutrients, or research platforms. Even within #1–60 there are important exceptions, so the three-category classification above is more scientifically defensible than calling every one of them simply “established.”

Endnotes — Exactly Matching 1–100

1. Acyclovir. Bryson YJ, Dillon M, Lovett M, Acuna G, Taylor S, Cherry JD, Johnson BL, Wiesmeier E, Growdon W, Creagh-Kirk T, Keeney R. Treatment of first episodes of genital herpes simplex virus infection with oral acyclovir: a randomized double-blind controlled trial in normal subjects. N Engl J Med. 1983;308(16):916-921. doi:10.1056/NEJM198304213081602.
2. Valacyclovir. Beutner KR, Friedman DJ, Forszpaniak C, Andersen PL, Wood MJ. Valaciclovir compared with acyclovir for improved therapy for herpes zoster in immunocompetent adults. Antimicrob Agents Chemother. 1995;39(7):1546-1553. doi:10.1128/AAC.39.7.1546.
3. Famciclovir. Tyring S, Barbarash RA, Nahlik JE, et al. Famciclovir for the treatment of acute herpes zoster: effects on acute disease and postherpetic neuralgia. Ann Intern Med. 1995;123(2):89-96. doi:10.7326/0003-4819-123-2-199507150-00002.
4. Penciclovir. Spruance SL, Rea TL, Thoming C, Tucker R, Saltzman R, Boon R. Penciclovir cream for the treatment of herpes simplex labialis: a randomized, multicenter, double-blind, placebo-controlled trial. JAMA. 1997;277(17):1374-1379.
5. Ganciclovir. Crumpacker CS. Ganciclovir.
   N Engl J Med. 1996;335(10):721-729. doi:10.1056/NEJM199609053351007.
6. Valganciclovir. Asberg A, Humar A, Rollag H, et al. Oral valganciclovir is noninferior to intravenous ganciclovir for the treatment of cytomegalovirus disease in solid organ transplant recipients. Am J Transplant. 2007;7(9):2106-2113. doi:10.1111/j.1600-6143.2007.01910.x.
7. Foscarnet. Wagstaff AJ, Bryson HM. Foscarnet: a reappraisal of its antiviral activity, pharmacokinetic properties and therapeutic use in immunocompromised patients with viral infections. Drugs. 1994;48(2):199-226.
8. Cidofovir. Lalezari JP, Holland GN, Kramer F, et al. Randomized, controlled study of the safety and efficacy of intravenous cidofovir for the treatment of relapsing cytomegalovirus retinitis in patients with AIDS. J Acquir Immune Defic Syndr Hum Retrovirol. 1998;17(4):339-344.
9. Letermovir. Marty FM, Ljungman P, Chemaly RF, et al. Letermovir prophylaxis for cytomegalovirus in hematopoietic-cell transplantation.
   N Engl J Med. 2017;377(25):2433-2444. doi:10.1056/NEJMoa1706640.
10. Maribavir. Avery RK, Alain S, Alexander BD, et al. Maribavir for refractory cytomegalovirus infections with or without resistance post-transplant: results from a phase 3 randomized clinical trial. Clin Infect Dis. 2022;75(4):690-701. doi:10.1093/cid/ciab988.
11. Trifluridine. Wilhelmus KR. Antiviral treatment and other therapeutic interventions for herpes simplex virus epithelial keratitis. Cochrane Database Syst Rev. 2015;(1):CD002898. doi:10.1002/14651858.CD002898.pub5.
12. Brivudine. Wassilew SW, Wutzler P; Brivudin Herpes Zoster Study Group. Oral brivudin in comparison with acyclovir for improved therapy of herpes zoster in immunocompetent patients. Antiviral Res. 2003;59(1):49-56.
13. Docosanol. Sacks SL, Thisted RA, Jones TM, et al. Clinical efficacy of topical docosanol 10% cream for herpes simplex labialis. J Am Acad Dermatol. 2001;45(2):222-230. doi:10.1067/mjd.2001.116215.
14. Oseltamivir. Treanor JJ, Hayden FG, Vrooman PS, et al. Efficacy and safety of the oral neuraminidase inhibitor oseltamivir in treating acute influenza: a randomized controlled trial. JAMA. 2000;283(8):1016-1024. doi:10.1001/jama.283.8.1016.
15. Zanamivir. Hayden FG, Osterhaus ADME, Treanor JJ, et al. Efficacy and safety of the neuraminidase inhibitor zanamivir in the treatment of influenzavirus infections.
    N Engl J Med. 1997;337(13):874-880. doi:10.1056/NEJM199709253371302.
16. Peramivir. Kohno S, Kida H, Mizuguchi M, Shimada J. Efficacy and safety of intravenous peramivir for treatment of seasonal influenza virus infection. Antimicrob Agents Chemother. 2010;54(11):4568-4574. doi:10.1128/AAC.00474-10.
17. Baloxavir marboxil. Hayden FG, Sugaya N, Hirotsu N, et al. Baloxavir marboxil for uncomplicated influenza in adults and adolescents.
    N Engl J Med. 2018;379(10):913-923. doi:10.1056/NEJMoa1716197.
18. Laninamivir octanoate. Watanabe A, Chang SC, Kim MJ, Chu DW, Ohashi Y; MARVEL Study Group. Long-acting neuraminidase inhibitor laninamivir octanoate versus oseltamivir for treatment of influenza. Clin Infect Dis. 2010;51(10):1167-1175. doi:10.1086/656802.
19. Favipiravir. Furuta Y, Komeno T, Nakamura T. Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase. Proc Jpn Acad Ser B Phys Biol Sci. 2017;93(7):449-463. doi:10.2183/pjab.93.027.
20. Ribavirin. Graci JD, Cameron CE. Mechanisms of action of ribavirin against distinct viruses. Rev Med Virol. 2006;16(1):37-48. doi:10.1002/rmv.483.
21. Nirmatrelvir/ritonavir. Hammond J, Leister-Tebbe H, Gardner A, et al. Oral nirmatrelvir for high-risk, nonhospitalized adults with Covid-19.
    N Engl J Med. 2022;386(15):1397-1408. doi:10.1056/NEJMoa2118542.
22. Remdesivir. Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the treatment of Covid-19—final report.
    N Engl J Med. 2020;383(19):1813-1826. doi:10.1056/NEJMoa2007764.
23. Molnupiravir. Jayk Bernal A, Gomes da Silva MM, Musungaie DB, et al. Molnupiravir for oral treatment of Covid-19 in nonhospitalized patients.
    N Engl J Med. 2022;386(6):509-520. doi:10.1056/NEJMoa2116044.
24. Tenofovir disoproxil fumarate. Marcellin P, Heathcote EJ, Buti M, et al. Tenofovir disoproxil fumarate versus adefovir dipivoxil for chronic hepatitis B.
    N Engl J Med. 2008;359(23):2442-2455. doi:10.1056/NEJMoa0802878.
25. Tenofovir alafenamide. Buti M, Gane E, Seto WK, et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of patients with HBeAg-negative chronic hepatitis B virus infection. Lancet Gastroenterol Hepatol. 2016;1(3):196-206. doi:10.1016/S2468-1253(16)30107-8.
26. Entecavir. Chang TT, Gish RG, de Man R, et al. A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B.
    N Engl J Med. 2006;354(10):1001-1010. doi:10.1056/NEJMoa051285.
27. Lamivudine. Lai CL, Chien RN, Leung NWY, et al. A one-year trial of lamivudine for chronic hepatitis B.
    N Engl J Med. 1998;339(2):61-68. doi:10.1056/NEJM199807093390201.
28. Adefovir dipivoxil. Marcellin P, Chang TT, Lim SG, et al. Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B.
    N Engl J Med. 2003;348(9):808-816. doi:10.1056/NEJMoa020681.
29. Telbivudine. Lai CL, Gane E, Liaw YF, et al. Telbivudine versus lamivudine in patients with chronic hepatitis B.
    N Engl J Med. 2007;357(25):2576-2588. doi:10.1056/NEJMoa066422.
30. Peginterferon alfa. Lau GKK, Piratvisuth T, Luo KX, et al. Peginterferon alfa-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitis B.
    N Engl J Med. 2005;352(26):2682-2695. doi:10.1056/NEJMoa043470.
31. Sofosbuvir. Lawitz E, Mangia A, Wyles D, et al. Sofosbuvir for previously untreated chronic hepatitis C infection.
    N Engl J Med. 2013;368(20):1878-1887. doi:10.1056/NEJMoa1214853.
32. Velpatasvir. Feld JJ, Jacobson IM, Hézode C, et al. Sofosbuvir and velpatasvir for HCV genotype 1, 2, 4, 5, and 6 infection.
    N Engl J Med. 2015;373(27):2599-2607. doi:10.1056/NEJMoa1512610.
33. Glecaprevir. Zeuzem S, Foster GR, Wang S, et al. Glecaprevir-pibrentasvir for 8 or 12 weeks in HCV genotype 1 or 3 infection.
    N Engl J Med. 2018;378(4):354-369. doi:10.1056/NEJMoa1702417.
34. Pibrentasvir. Zeuzem S, Foster GR, Wang S, et al. Glecaprevir-pibrentasvir for 8 or 12 weeks in HCV genotype 1 or 3 infection.
    N Engl J Med. 2018;378(4):354-369. doi:10.1056/NEJMoa1702417.
35. Ledipasvir. Afdhal N, Zeuzem S, Kwo P, et al. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection.
    N Engl J Med. 2014;370(20):1889-1898. doi:10.1056/NEJMoa1402454.
36. Voxilaprevir. Bourlière M, Gordon SC, Flamm SL, et al. Sofosbuvir, velpatasvir, and voxilaprevir for previously treated HCV infection.
    N Engl J Med. 2017;376(22):2134-2146. doi:10.1056/NEJMoa1613512.
37. Elbasvir. Zeuzem S, Ghalib R, Reddy KR, et al. Grazoprevir-elbasvir combination therapy for treatment-naive cirrhotic and noncirrhotic patients with chronic hepatitis C virus genotype 1, 4, or 6 infection. Ann Intern Med. 2015;163(1):1-13. doi:10.7326/M15-0785.
38. Grazoprevir. Zeuzem S, Ghalib R, Reddy KR, et al. Grazoprevir-elbasvir combination therapy for treatment-naive cirrhotic and noncirrhotic patients with chronic hepatitis C virus genotype 1, 4, or 6 infection. Ann Intern Med. 2015;163(1):1-13. doi:10.7326/M15-0785.
39. Dolutegravir. Walmsley SL, Antela A, Clumeck N, et al. Dolutegravir plus abacavir-lamivudine for the treatment of HIV-1 infection.
    N Engl J Med. 2013;369(19):1807-1818. doi:10.1056/NEJMoa1215541.
40. Bictegravir. Gallant J, Lazzarin A, Mills A, et al. Bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection. Lancet. 2017;390(10107):2063-2072. doi:10.1016/S0140-6736(17)32299-7.
41. Raltegravir. Lennox JL, DeJesus E, Lazzarin A, et al. Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-naive patients with HIV-1 infection. Lancet. 2009;374(9692):796-806. doi:10.1016/S0140-6736(09)60918-1.
42. Cabotegravir. Swindells S, Andrade-Villanueva JF, Richmond GJ, et al. Long-acting cabotegravir and rilpivirine for maintenance of HIV-1 suppression.
    N Engl J Med. 2020;382(12):1112-1123. doi:10.1056/NEJMoa1904398.
43. Darunavir. Clotet B, Bellos N, Molina JM, et al. Efficacy and safety of darunavir-ritonavir at week 48 in treatment-experienced patients with HIV-1 infection. Lancet. 2007;369(9568):1169-1178. doi:10.1016/S0140-6736(07)60497-8.
44. Atazanavir. Molina JM, Andrade-Villanueva J, Echevarria J, et al. Once-daily atazanavir/ritonavir versus twice-daily lopinavir/ritonavir in treatment-naive HIV-1-infected patients. Lancet. 2008;372(9639):646-655. doi:10.1016/S0140-6736(08)61081-8.
45. Maraviroc. Gulick RM, Lalezari J, Goodrich J, et al. Maraviroc for previously treated patients with R5 HIV-1 infection.
    N Engl J Med. 2008;359(14):1429-1441. doi:10.1056/NEJMoa0803152.
46. Enfuvirtide. Lalezari JP, Henry K, O’Hearn M, et al. Enfuvirtide, an HIV-1 fusion inhibitor, for drug-resistant HIV infection in North and South America.
    N Engl J Med. 2003;348(22):2175-2185. doi:10.1056/NEJMoa035026.
47. Fostemsavir. Kozal M, Aberg J, Pialoux G, et al. Fostemsavir in adults with multidrug-resistant HIV-1 infection.
    N Engl J Med. 2020;382(13):1232-1243. doi:10.1056/NEJMoa1902493.
48. Ibalizumab. Emu B, Fessel J, Schrader S, et al. Phase 3 study of ibalizumab for multidrug-resistant HIV-1.
    N Engl J Med. 2018;379(7):645-654. doi:10.1056/NEJMoa1711460.
49. Lenacapavir. Segal-Maurer S, DeJesus E, Stellbrink HJ, et al. Capsid inhibition with lenacapavir in multidrug-resistant HIV-1 infection.
    N Engl J Med. 2022;386(19):1793-1803. doi:10.1056/NEJMoa2115542.
50. Doravirine. Molina JM, Squires K, Sax PE, et al. Doravirine versus ritonavir-boosted darunavir in antiretroviral-naive adults with HIV-1. Lancet HIV. 2018;5(5):e211-e220. doi:10.1016/S2352-3018(18)30021-3.
51. Efavirenz. Staszewski S, Morales-Ramirez J, Tashima KT, et al. Efavirenz plus zidovudine and lamivudine, efavirenz plus indinavir, and indinavir plus zidovudine and lamivudine in treatment-naive HIV patients.
    N Engl J Med. 1999;341(25):1865-1873. doi:10.1056/NEJM199912163412501.
52. Emtricitabine. Gallant JE, DeJesus E, Arribas JR, et al. Tenofovir DF, emtricitabine, and efavirenz versus zidovudine, lamivudine, and efavirenz for HIV.
    N Engl J Med. 2006;354(3):251-260. doi:10.1056/NEJMoa051871.
53. Zidovudine. Fischl MA, Richman DD, Grieco MH, et al. The efficacy of azidothymidine in the treatment of patients with AIDS and AIDS-related complex.
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54. Tecovirimat. Grosenbach DW, Honeychurch K, Rose EA, et al. Oral tecovirimat for the treatment of smallpox.
    N Engl J Med. 2018;379(1):44-53. doi:10.1056/NEJMoa1705688. This study combined efficacy in nonhuman primates and rabbits with human PK/safety data.
55. Brincidofovir. Hostetler KY. Alkoxyalkyl prodrugs of acyclic nucleoside phosphonates enhance oral antiviral activity and reduce toxicity: current state of the art. Antiviral Res. 2009;82(2):A84-A98. doi:10.1016/j.antiviral.2009.01.005.
56. Palivizumab. IMpact-RSV Study Group. Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants. Pediatrics. 1998;102(3 Pt 1):531-537. doi:10.1542/peds.102.3.531.
57. Nirsevimab. Hammitt LL, Dagan R, Yuan Y, et al. Nirsevimab for prevention of RSV in healthy late-preterm and term infants.
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58. Interferon alfa. Hoofnagle JH, Peters M, Mullen KD, et al. Randomized, controlled trial of recombinant human alpha-interferon in patients with chronic hepatitis B. Gastroenterology. 1988;95(5):1318-1325.
59. Peginterferon lambda. Reis G, Moreira Silva EAS, Medeiros Silva DC, et al. Early treatment with pegylated interferon lambda for Covid-19.
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60. Amantadine. Jefferson T, Demicheli V, Di Pietrantonj C, Rivetti D. Amantadine and rimantadine for influenza A in adults. Cochrane Database Syst Rev. 2006;(2):CD001169. doi:10.1002/14651858.CD001169.pub3.
61. Quercetin. Di Petrillo A, Orrù G, Fais A, Fantini MC. Quercetin and its derivates as antiviral potentials: a comprehensive review. Phytother Res. 2022;36(1):266-278. doi:10.1002/ptr.7309. PMID:34709675.
62. Baicalein. Liu XY, Xie W, Zhou HY, Zhang HQ, Jin YS. A comprehensive overview on antiviral effects of baicalein and its glucuronide derivative baicalin. J Integr Med. 2024;22(6):621-636. PMID:39368944.
63. Baicalin. Li K, Liang Y, Cheng A, et al. Antiviral properties of baicalin: a concise review. Rev Bras Farmacogn. 2021;31:408-419. doi:10.1007/s43450-021-00182-1. PMID:34642508.
64. EGCG. Xu J, Xu Z, Zheng W. A review of the antiviral role of green tea catechins. Molecules. 2017;22(8):1337. doi:10.3390/molecules22081337. PMID:28805687.
65. Curcumin. Jennings MR, Parks RJ. Curcumin as an antiviral agent. Viruses. 2020;12(11):1242. doi:10.3390/v12111242. PMID:33142686.
66. Resveratrol. Abba Y, Hassim H, Hamzah H, Noordin MM. Antiviral activity of resveratrol against human and animal viruses. Adv Virol. 2015;2015:184241. doi:10.1155/2015/184241. PMID:26693226.
67. Andrographolide. Jiang M, Sheng F, Zhang Z, et al. Andrographolide as a potent and promising antiviral agent. Chin J Nat Med. 2020;18(10):760-769.
68. Glycyrrhizin. Fiore C, Eisenhut M, Krausse R, et al. Antiviral effects of Glycyrrhiza species. Phytother Res. 2008;22(2):141-148. doi:10.1002/ptr.2295.
69. Berberine. Warowicka A, Nawrot R, Goździcka-Józefiak A. Antiviral activity of berberine. Arch Virol. 2020;165(9):1935-1945. doi:10.1007/s00705-020-04706-3.
70. Apigenin. Zakaryan H, Arabyan E, Oo A, Zandi K. Flavonoids: promising natural compounds against viral infections. Arch Virol. 2017;162(9):2539-2551. doi:10.1007/s00705-017-3417-y.
71. Luteolin. Peng M, Watanabe S, Chan KWK, et al. Luteolin restricts dengue virus replication through inhibition of the proprotein convertase furin. Antiviral Res. 2017;143:176-185. doi:10.1016/j.antiviral.2017.03.026.
72. Kaempferol. Zakaryan H, Arabyan E, Oo A, Zandi K. Flavonoids: promising natural compounds against viral infections. Arch Virol. 2017;162(9):2539-2551. doi:10.1007/s00705-017-3417-y.
73. Myricetin. Zakaryan H, Arabyan E, Oo A, Zandi K. Flavonoids: promising natural compounds against viral infections. Arch Virol. 2017;162(9):2539-2551. doi:10.1007/s00705-017-3417-y.
74. Hesperidin. Zakaryan H, Arabyan E, Oo A, Zandi K. Flavonoids: promising natural compounds against viral infections. Arch Virol. 2017;162(9):2539-2551. doi:10.1007/s00705-017-3417-y.
75. Naringenin. Tutunchi H, Naeini F, Ostadrahimi A, Hosseinzadeh-Attar MJ. Naringenin, a flavanone with antiviral and anti-inflammatory effects: a promising treatment strategy against COVID-19. Phytother Res. 2020;34(12):3137-3147. doi:10.1002/ptr.6781.
76. Genistein. Andres A, Donovan SM, Kuhlenschmidt MS. Soy isoflavones and virus infections. J Nutr Biochem. 2009;20(8):563-569. doi:10.1016/j.jnutbio.2009.04.004.
77. Silymarin/silibinin. Polyak SJ, Morishima C, Shuhart MC, Wang CC, Liu Y, Lee DYW. Inhibition of T-cell inflammatory cytokines, hepatocyte NF-κB signaling, and HCV infection by standardized silymarin. Gastroenterology. 2007;132(5):1925-1936. doi:10.1053/j.gastro.2007.02.038.
78. Epicatechin gallate. Xu J, Xu Z, Zheng W. A review of the antiviral role of green tea catechins. Molecules. 2017;22(8):1337. doi:10.3390/molecules22081337.
79. Theaflavins. Chowdhury P, Barooah AK. Tea bioactive modulate innate immunity: in perception to COVID-19 pandemic. Front Immunol. 2020;11:590716. doi:10.3389/fimmu.2020.590716.
80. Allicin. Rouf R, Uddin SJ, Sarker DK, et al. Antiviral potential of garlic (Allium sativum) and its organosulfur compounds: a systematic update of pre-clinical and clinical data. Trends Food Sci Technol. 2020;104:219-234. doi:10.1016/j.tifs.2020.08.006. Recent mechanistic review also emphasizes instability and limited clinical translation.
81. Ajoene. Rouf R, Uddin SJ, Sarker DK, et al. Antiviral potential of garlic (Allium sativum) and its organosulfur compounds: a systematic update of pre-clinical and clinical data. Trends Food Sci Technol. 2020;104:219-234. doi:10.1016/j.tifs.2020.08.006.
82. Elderberry. Hawkins J, Baker C, Cherry L, Dunne E. Black elderberry (Sambucus nigra) supplementation effectively treats upper respiratory symptoms: a meta-analysis of randomized, controlled clinical trials. Complement Ther Med. 2019;42:361-365. doi:10.1016/j.ctim.2018.12.004.
83. Echinacea. Karsch-Völk M, Barrett B, Kiefer D, Bauer R, Ardjomand-Woelkart K, Linde K. Echinacea for preventing and treating the common cold. Cochrane Database Syst Rev. 2014;(2):CD000530. doi:10.1002/14651858.CD000530.pub3.
84. Lactoferrin. Berlutti F, Pantanella F, Natalizi T, et al. Antiviral properties of lactoferrin—a natural immunity molecule. Molecules. 2011;16(8):6992-7018. doi:10.3390/molecules16086992. PMID:21847071.
85. Glycerol monolaurate/monolaurin. Thormar H, Isaacs CE, Brown HR, Barshatzky MR, Pessolano T. Inactivation of enveloped viruses and killing of cells by fatty acids and monoglycerides. Antimicrob Agents Chemother. 1987;31(1):27-31. doi:10.1128/AAC.31.1.27.
86. Lauric acid. Thormar H, Isaacs CE, Brown HR, Barshatzky MR, Pessolano T. Inactivation of enveloped viruses and killing of cells by fatty acids and monoglycerides. Antimicrob Agents Chemother. 1987;31(1):27-31. doi:10.1128/AAC.31.1.27.
87. Melatonin. Reiter RJ, Ma Q, Sharma R. Treatment of Ebola and other infectious diseases: melatonin “goes viral.” Melatonin Res. 2020;3(1):43-57. doi:10.32794/mr11250047.
88. Sulforaphane. Ordonez AA, Bullen CK, Villabona-Rueda AF, et al. Sulforaphane exhibits antiviral activity against pandemic SARS-CoV-2 and seasonal HCoV-OC43 coronaviruses in vitro and in mice. Commun Biol. 2022;5:242. doi:10.1038/s42003-022-03189-z.
89. Propolis. Schnitzler P, Neuner A, Nolkemper S, et al. Antiviral activity and mode of action of propolis extracts and selected compounds. Phytother Res. 2010;24(Suppl 1):S20-S28. doi:10.1002/ptr.2868. PMID:19472427.
90. Caffeic acid phenethyl ester. Shen H, Yamashita A, Nakakoshi M, et al. Inhibitory effects of caffeic acid phenethyl ester derivatives on replication of hepatitis C virus. PLoS One. 2013;8(12):e82299. doi:10.1371/journal.pone.0082299. PMID:24358168.
91. Eugenol. Guo D, et al. Antiviral properties of the natural product eugenol: a review. 2025. PMID:40513765. The review covers human and animal-virus research and emphasizes that rigorously designed antiviral studies remain necessary.
92. Carvacrol. Pilau MR, Alves SH, Weiblen R, Arenhart S, Cueto AP, Lovato LT. Antiviral activity of the Lippia graveolens (Mexican oregano) essential oil and its main compound carvacrol against human and animal viruses. Braz J Microbiol. 2011;42(4):1616-1624. doi:10.1590/S1517-83822011000400049.
93. Thymol. Schnitzler P, Koch C, Reichling J. Susceptibility of drug-resistant clinical herpes simplex virus type 1 strains to essential oils of ginger, thyme, hyssop, and sandalwood. Antimicrob Agents Chemother. 2007;51(5):1859-1862. doi:10.1128/AAC.00426-06.
94. Cinnamaldehyde. Hayashi K, Imanishi N, Kashiwayama Y, et al. Inhibitory effect of cinnamaldehyde, derived from Cinnamomi cortex, on the growth of influenza A/PR/8 virus in vitro and in vivo. Antiviral Res. 2007;74(1):1-8.
95. β-Glucans. Atoom AM, et al. β-Glucan in antiviral defense: mechanisms, immune modulation, and therapeutic prospects. Folia Microbiol (Praha). 2025;70(6):1135-1157. doi:10.1007/s12223-025-01345-6.
96. Ganoderma lucidum. Suwannarach N, Kumla J, Sujarit K, et al. Medicinal fungi with antiviral effect. Molecules. 2022;27(14):4457. doi:10.3390/molecules27144457. PMID:35889330. The review covers Ganoderma antiviral compounds in human and animal-virus models.
97. Cordyceps/cordycepin. Suwannarach N, Kumla J, Sujarit K, et al. Medicinal fungi with antiviral effect. Molecules. 2022;27(14):4457. doi:10.3390/molecules27144457. PMID:35889330.
98. Sulfated polysaccharides. Ghosh T, Chattopadhyay K, Marschall M, Karmakar P, Mandal P, Ray B. Focus on antivirally active sulfated polysaccharides: from structure-activity analysis to clinical evaluation. Glycobiology. 2009;19(1):2-15. doi:10.1093/glycob/cwn092. PMID:18815291. More recent reviews likewise describe activity at adsorption, invasion, transcription and replication stages.
99. Zinc. Read SA, Obeid S, Ahlenstiel C, Ahlenstiel G. The role of zinc in antiviral immunity. Adv Nutr. 2019;10(4):696-710. doi:10.1093/advances/nmz013. PMID:31305906. The review covers direct antiviral actions, mammalian immune biology and human clinical evidence while emphasizing remaining uncertainty regarding therapeutic supplementation.
100. Selenium. Harthill M. Review: micronutrient selenium deficiency influences evolution of some viral infectious diseases. Biol Trace Elem Res. 2011;143(3):1325-1336. doi:10.1007/s12011-011-8977-1.

Top 100 Antivirals, With a Reference After Every Item

1. Acyclovir

HSV-1, HSV-2, VZV. Selectively activated in herpesvirus-infected cells and inhibits viral DNA polymerase.

Reference: Whitley RJ, Gnann JW Jr. Acyclovir: a decade later.
N Engl J Med. 1992;327(11):782-789. doi:10.1056/NEJM199209103271108.

2. Valacyclovir

HSV-1, HSV-2, VZV. Highly bioavailable oral prodrug of acyclovir.

Reference: Beutner KR, Friedman DJ, Forszpaniak C, Andersen PL, Wood MJ. Valaciclovir compared with acyclovir for improved therapy for herpes zoster in immunocompetent adults. Antimicrob Agents Chemother. 1995;39(7):1546-1553. doi:10.1128/AAC.39.7.1546.

3. Famciclovir

HSV and VZV. Oral prodrug of penciclovir.

Reference: Tyring S, Barbarash RA, Nahlik JE, et al. Famciclovir for the treatment of acute herpes zoster. Ann Intern Med. 1995;123(2):89-96.

4. Penciclovir

HSV. Guanosine analogue used particularly as topical treatment for herpes labialis.

Reference: Spruance SL, Rea TL, Thoming C, Tucker R, Saltzman R, Boon R. Penciclovir cream for the treatment of herpes simplex labialis. JAMA. 1997;277(17):1374-1379.

5. Ganciclovir

CMV. Major viral-DNA-polymerase inhibitor for serious CMV disease.

Reference: Crumpacker CS. Ganciclovir.
N Engl J Med. 1996;335(10):721-729. doi:10.1056/NEJM199609053351007.

6. Valganciclovir

CMV. Orally bioavailable ganciclovir prodrug.

Reference: Asberg A, Humar A, Rollag H, et al. Oral valganciclovir is noninferior to intravenous ganciclovir for treatment of cytomegalovirus disease in solid-organ transplant recipients. Am J Transplant. 2007;7(9):2106-2113.

7. Foscarnet

Resistant CMV and HSV. Direct viral DNA-polymerase inhibitor that does not require viral kinase activation.

Reference: Wagstaff AJ, Bryson HM. Foscarnet: a reappraisal of its antiviral activity, pharmacokinetic properties and therapeutic use. Drugs. 1994;48(2):199-226.

8. Cidofovir

CMV and other DNA viruses. Nucleotide analogue with broad laboratory activity against DNA viruses.

Reference: Lalezari JP, Holland GN, Kramer F, et al. Randomized controlled study of intravenous cidofovir for relapsing cytomegalovirus retinitis. J Acquir Immune Defic Syndr Hum Retrovirol. 1998;17(4):339-344.

9. Letermovir

CMV. Inhibits the CMV terminase complex rather than DNA polymerase.

Reference: Marty FM, Ljungman P, Chemaly RF, et al. Letermovir prophylaxis for cytomegalovirus in hematopoietic-cell transplantation.
N Engl J Med. 2017;377:2433-2444. doi:10.1056/NEJMoa1706640.

10. Maribavir

Refractory/resistant CMV. Targets CMV UL97 kinase.

Reference: Avery RK, Alain S, Alexander BD, et al. Maribavir for refractory cytomegalovirus infections with or without resistance post-transplant. Clin Infect Dis. 2022;75(4):690-701. doi:10.1093/cid/ciab988.

11. Trifluridine

HSV keratitis. Fluorinated pyrimidine nucleoside analogue primarily used ophthalmically.

Reference: De Clercq E. Antiviral drugs in current clinical use. J Clin Virol. 2004;30(2):115-133.

12. Brivudine

VZV/HSV-1. Potent thymidine-nucleoside analogue used for herpes zoster in several countries.

Reference: De Clercq E. Antiviral drugs in current clinical use. J Clin Virol. 2004;30(2):115-133.

13. Docosanol

Herpes labialis. Topical long-chain alcohol that interferes with HSV entry/fusion.

Reference: Sacks SL, Thisted RA, Jones TM, et al. Clinical efficacy of topical docosanol 10% cream for herpes simplex labialis. J Am Acad Dermatol. 2001;45(2):222-230. doi:10.1067/mjd.2001.116215.

14. Oseltamivir

Influenza A/B. Oral neuraminidase inhibitor.

Reference: Treanor JJ, Hayden FG, Vrooman PS, et al. Efficacy and safety of oral oseltamivir in treating acute influenza. JAMA. 2000;283(8):1016-1024.

15. Zanamivir

Influenza A/B. Inhaled neuraminidase inhibitor.

Reference: Hayden FG, Osterhaus ADME, Treanor JJ, et al. Efficacy and safety of zanamivir in treatment of influenza virus infections.
N Engl J Med. 1997;337:874-880.

16. Peramivir

Influenza A/B. Intravenous neuraminidase inhibitor.

Reference: Kohno S, Kida H, Mizuguchi M, Shimada J. Efficacy and safety of intravenous peramivir for seasonal influenza. Antimicrob Agents Chemother. 2010;54(11):4568-4574.

17. Baloxavir Marboxil

Influenza A/B. Inhibits viral cap-dependent endonuclease.

Reference: Hayden FG, Sugaya N, Hirotsu N, et al. Baloxavir marboxil for uncomplicated influenza in adults and adolescents.
N Engl J Med. 2018;379:913-923. doi:10.1056/NEJMoa1716197.

18. Laninamivir Octanoate

Influenza. Long-acting inhaled neuraminidase inhibitor used in Japan.

Reference: Watanabe A, Chang SC, Kim MJ, Chu DW, Ohashi Y. Long-acting neuraminidase inhibitor laninamivir octanoate versus oseltamivir for influenza. Clin Infect Dis. 2010;51(10):1167-1175.

19. Favipiravir

RNA viruses/influenza. RNA-dependent RNA-polymerase inhibitor with laboratory activity across several RNA-virus families; approved uses vary by country.

Reference: Furuta Y, Komeno T, Nakamura T. Favipiravir, a broad spectrum inhibitor of viral RNA polymerase. Proc Jpn Acad Ser B. 2017;93(7):449-463.

20. Ribavirin

RSV and selected RNA viruses. Broad-spectrum nucleoside analogue with highly indication-dependent clinical utility.

Reference: Graci JD, Cameron CE. Mechanisms of action of ribavirin against distinct viruses. Rev Med Virol. 2006;16(1):37-48.

21. Nirmatrelvir/Ritonavir

SARS-CoV-2. Nirmatrelvir inhibits SARS-CoV-2 main protease.

Reference: Hammond J, Leister-Tebbe H, Gardner A, et al. Oral nirmatrelvir for high-risk, nonhospitalized adults with Covid-19.
N Engl J Med. 2022;386:1397-1408.

22. Remdesivir

SARS-CoV-2. Nucleotide analogue targeting viral RNA polymerase.

Reference: Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the treatment of Covid-19—final report.
N Engl J Med. 2020;383:1813-1826.

23. Molnupiravir

SARS-CoV-2. Nucleoside analogue causing lethal viral mutagenesis; clinical use is more restricted than first-line agents.

Reference: Jayk Bernal A, Gomes da Silva MM, Musungaie DB, et al. Molnupiravir for oral treatment of Covid-19 in nonhospitalized patients.
N Engl J Med. 2022;386:509-520.

24. Tenofovir Disoproxil Fumarate

HBV/HIV. Potent nucleotide reverse-transcriptase inhibitor.

Reference: Marcellin P, Heathcote EJ, Buti M, et al. Tenofovir disoproxil fumarate versus adefovir dipivoxil for chronic hepatitis B.
N Engl J Med. 2008;359:2442-2455.

25. Tenofovir Alafenamide

HBV/HIV. Tenofovir prodrug producing greater intracellular exposure with lower systemic tenofovir levels.

Reference: Buti M, Gane E, Seto WK, et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate for HBeAg-negative chronic hepatitis B. Lancet Gastroenterol Hepatol. 2016;1(3):196-206.

26. Entecavir

HBV. Potent HBV polymerase/reverse-transcriptase inhibitor.

Reference: Chang TT, Gish RG, de Man R, et al. Entecavir compared with lamivudine for HBeAg-positive chronic hepatitis B.
N Engl J Med. 2006;354:1001-1010.

27. Lamivudine

HBV/HIV. Effective nucleoside reverse-transcriptase inhibitor, although HBV resistance develops more readily than with newer agents.

Reference: Lai CL, Chien RN, Leung NWY, et al. A one-year trial of lamivudine for chronic hepatitis B.
N Engl J Med. 1998;339:61-68.

28. Adefovir Dipivoxil

HBV. Older nucleotide analogue largely superseded by more potent agents.

Reference: Marcellin P, Chang TT, Lim SG, et al. Adefovir dipivoxil for HBeAg-positive chronic hepatitis B.
N Engl J Med. 2003;348:808-816.

29. Telbivudine

HBV. Thymidine nucleoside analogue; resistance limits contemporary use.

Reference: Lai CL, Gane E, Liaw YF, et al. Telbivudine versus lamivudine in patients with chronic hepatitis B.
N Engl J Med. 2007;357:2576-2588.

30. Peginterferon Alfa

HBV and historically HCV. Host-directed interferon antiviral/immunomodulator.

Reference: Lau GKK, Piratvisuth T, Luo KX, et al. Peginterferon alfa-2a, lamivudine, and combination for HBeAg-positive chronic hepatitis B.
N Engl J Med. 2005;352:2682-2695.

31. Sofosbuvir

HCV. NS5B nucleotide-polymerase inhibitor.

Reference: Lawitz E, Mangia A, Wyles D, et al. Sofosbuvir for previously untreated chronic hepatitis C infection.
N Engl J Med. 2013;368:1878-1887.

32. Velpatasvir

HCV. Pangenotypic NS5A inhibitor.

Reference: Feld JJ, Jacobson IM, Hézode C, et al. Sofosbuvir and velpatasvir for HCV infection.
N Engl J Med. 2015;373:2599-2607.

33. Glecaprevir

HCV. Pangenotypic NS3/4A protease inhibitor.

Reference: Zeuzem S, Foster GR, Wang S, et al. Glecaprevir-pibrentasvir for HCV genotype 1 or 3 infection.
N Engl J Med. 2018;378:354-369.

34. Pibrentasvir

HCV. Pangenotypic NS5A inhibitor paired with glecaprevir.

Reference: Zeuzem S, Foster GR, Wang S, et al. Glecaprevir-pibrentasvir for HCV genotype 1 or 3 infection.
N Engl J Med. 2018;378:354-369.

35. Ledipasvir

HCV. NS5A inhibitor used with sofosbuvir.

Reference: Afdhal N, Zeuzem S, Kwo P, et al. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection.
N Engl J Med. 2014;370:1889-1898.

36. Voxilaprevir

HCV. NS3/4A protease inhibitor incorporated into rescue DAA therapy.

Reference: Bourlière M, Gordon SC, Flamm SL, et al. Sofosbuvir, velpatasvir, and voxilaprevir for previously treated HCV infection.
N Engl J Med. 2017;376:2134-2146.

37. Elbasvir

HCV. NS5A inhibitor.

Reference: Sperl J, Horvath G, Halota W, et al. Efficacy and safety of elbasvir/grazoprevir versus sofosbuvir/peginterferon/ribavirin. J Hepatol. 2016;65(6):1112-1119.

38. Grazoprevir

HCV. NS3/4A protease inhibitor used with elbasvir.

Reference: Sperl J, Horvath G, Halota W, et al. Efficacy and safety of elbasvir/grazoprevir versus sofosbuvir/peginterferon/ribavirin. J Hepatol. 2016;65(6):1112-1119.

39. Dolutegravir

HIV. Integrase strand-transfer inhibitor with a high resistance barrier.

Reference: Walmsley SL, Antela A, Clumeck N, et al. Dolutegravir plus abacavir-lamivudine for treatment of HIV-1 infection.
N Engl J Med. 2013;369:1807-1818.

40. Bictegravir

HIV. Potent integrase inhibitor.

Reference: Gallant J, Lazzarin A, Mills A, et al. Bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine. Lancet. 2017;390:2063-2072.

41. Raltegravir

HIV. First-in-class integrase inhibitor.

Reference: Lennox JL, DeJesus E, Lazzarin A, et al. Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy. Lancet. 2009;374:796-806.

42. Cabotegravir

HIV. Long-acting integrase inhibitor used in treatment and prevention strategies.

Reference: Swindells S, Andrade-Villanueva JF, Richmond GJ, et al. Long-acting cabotegravir and rilpivirine for maintenance of HIV-1 suppression.
N Engl J Med. 2020;382:1112-1123.

43. Darunavir

HIV. Protease inhibitor with a high genetic barrier to resistance.

Reference: Clotet B, Bellos N, Molina JM, et al. Darunavir-ritonavir at week 48 in treatment-experienced patients. Lancet. 2007;369:1169-1178.

44. Atazanavir

HIV. HIV protease inhibitor.

Reference: Molina JM, Andrade-Villanueva J, Echevarria J, et al. Once-daily atazanavir/ritonavir versus lopinavir/ritonavir. Lancet. 2008;372:646-655.

45. Maraviroc

HIV. CCR5 antagonist preventing viral entry into susceptible cells.

Reference: Gulick RM, Lalezari J, Goodrich J, et al. Maraviroc for previously treated patients with R5 HIV-1 infection.
N Engl J Med. 2008;359:1429-1441.

46. Enfuvirtide

HIV. Peptide inhibitor of gp41-mediated membrane fusion.

Reference: Lalezari JP, Henry K, O’Hearn M, et al. Enfuvirtide, an HIV-1 fusion inhibitor, for drug-resistant HIV infection.
N Engl J Med. 2003;348:2175-2185.

47. Fostemsavir

Multidrug-resistant HIV. Attachment inhibitor targeting gp120.

Reference: Kozal M, Aberg J, Pialoux G, et al. Fostemsavir in adults with multidrug-resistant HIV-1 infection.
N Engl J Med. 2020;382:1232-1243.

48. Ibalizumab

Multidrug-resistant HIV. Monoclonal antibody targeting CD4 and blocking post-attachment entry.

Reference: Emu B, Fessel J, Schrader S, et al. Phase 3 study of ibalizumab for multidrug-resistant HIV-1.
N Engl J Med. 2018;379:645-654.

49. Lenacapavir

HIV. Long-acting first-in-class capsid inhibitor.

Reference: Segal-Maurer S, DeJesus E, Stellbrink HJ, et al. Capsid inhibition with lenacapavir in multidrug-resistant HIV-1 infection.
N Engl J Med. 2022;386:1793-1803.

50. Doravirine

HIV. Non-nucleoside reverse-transcriptase inhibitor.

Reference: Molina JM, Squires K, Sax PE, et al. Doravirine versus ritonavir-boosted darunavir in treatment-naive adults with HIV-1. Lancet HIV. 2018;5:e211-e220.

51. Efavirenz

HIV. NNRTI with extensive clinical experience.

Reference: Staszewski S, Morales-Ramirez J, Tashima KT, et al. Efavirenz plus zidovudine and lamivudine.
N Engl J Med. 1999;341:1865-1873.

52. Emtricitabine

HIV/HBV activity. Nucleoside reverse-transcriptase inhibitor commonly paired with tenofovir.

Reference: Gallant JE, DeJesus E, Arribas JR, et al. Tenofovir DF, emtricitabine, and efavirenz versus zidovudine, lamivudine, and efavirenz.
N Engl J Med. 2006;354:251-260.

53. Zidovudine

HIV. Historically the first widely used antiretroviral nucleoside analogue.

Reference: Fischl MA, Richman DD, Grieco MH, et al. The efficacy of azidothymidine in AIDS and AIDS-related complex.
N Engl J Med. 1987;317:185-191.

54. Tecovirimat

Variola/smallpox. Blocks orthopoxvirus VP37-mediated viral dissemination. Human efficacy against smallpox cannot be conventionally tested; approval relied substantially on animal efficacy data.

Reference: Grosenbach DW, Honeychurch K, Rose EA, et al. Oral tecovirimat for the treatment of smallpox.
N Engl J Med. 2018;379:44-53.

55. Brincidofovir

Smallpox/DNA viruses. Lipid conjugate of cidofovir with broad anti-DNA-virus activity.

Reference: De Clercq E. Highlights in antiviral drug research: antivirals at the horizon. Med Res Rev. 2013;33(6):1215-1248. doi:10.1002/med.21256.

56. Palivizumab

RSV prevention. Anti-RSV F-protein monoclonal antibody; prophylactic, not treatment of established infection.

Reference: IMpact-RSV Study Group. Palivizumab reduces hospitalization from respiratory syncytial virus infection in high-risk infants. Pediatrics. 1998;102:531-537.

57. Nirsevimab

RSV prevention. Long-acting monoclonal antibody against prefusion RSV F protein.

Reference: Hammitt LL, Dagan R, Yuan Y, et al. Nirsevimab for prevention of RSV in healthy late-preterm and term infants.
N Engl J Med. 2022;386:837-846.

58. Interferon Alfa

Multiple viruses. Host antiviral cytokine with historical and selected contemporary therapeutic roles.

Reference: De Clercq E. Antiviral drugs: current state of the art. J Clin Virol. 2001;22(1):73-89.

59. Interferon Lambda

Experimental/limited clinical antiviral applications. Type III interferon that emphasizes epithelial antiviral defenses.

Reference: Feld JJ, Kandel C, Biondi MJ, et al. Peginterferon lambda for the treatment of outpatients with COVID-19.
N Engl J Med. 2023;388:518-528.

60. Amantadine

Influenza A, historical. M2 ion-channel blocker; widespread influenza resistance has largely eliminated routine use.

Reference: Jefferson T, Deeks JJ, Demicheli V, Rivetti D, Rudin M. Amantadine and rimantadine for influenza A. Cochrane Database Syst Rev. 2004;(3):CD001169.

61. Quercetin

Flavonoid. Broad in-vitro antiviral activity involving viral entry, enzymes and host pathways; human therapeutic evidence remains limited.

Reference: Di Petrillo A, Orrù G, Fais A, Fantini MC. Quercetin and its derivates as antiviral potentials: a comprehensive review. Phytother Res. 2022;36(1):266-278. doi:10.1002/ptr.7309.

62. Baicalein

Scutellaria baicalensis. Experimental activity against influenza, flaviviruses, coronaviruses and other viruses.

Reference: Liu XY, Xie W, Zhou HY, Zhang HQ, Jin YS. A comprehensive overview on antiviral effects of baicalein and baicalin. J Integr Med. 2024;22(6):621-636.

63. Baicalin

Scutellaria flavonoid. Experimental antiviral and immunomodulatory effects.

Reference: Li K, Liang Y, Cheng A, et al. Antiviral properties of baicalin: a concise review. Rev Bras Farmacogn. 2021;31:408-419.

64. EGCG

Green tea catechin. Experimental effects on attachment, entry and replication of multiple viruses.

Reference: Xu J, Xu Z, Zheng W. A review of the antiviral role of green tea catechins. Molecules. 2017;22(8):1337.

65. Curcumin

Turmeric. Broad in-vitro activity against enveloped and non-enveloped viruses; pharmacokinetic limitations are substantial.

Reference: Jennings MR, Parks RJ. Curcumin as an antiviral agent. Viruses. 2020;12(11):1242.

66. Resveratrol

Grapes/berries/polyphenol. Experimental antiviral effects against several DNA and RNA viruses.

Reference: Abba Y, Hassim H, Hamzah H, Noordin MM. Antiviral activity of resveratrol against human and animal viruses. Adv Virol. 2015;2015:184241.

67. Andrographolide

Andrographis paniculata. Diterpenoid with broad experimental antiviral activity.

Reference: Jiang M, Sheng F, Zhang Z, et al. Andrographolide as a potent and promising antiviral agent. Chin J Nat Med. 2020;18(10):760-769.

68. Glycyrrhizin

Licorice root. Experimental activity against several viruses; excessive use can cause hypokalemia and hypertension.

Reference: Fiore C, Eisenhut M, Krausse R, et al. Antiviral effects of Glycyrrhiza species. Phytother Res. 2008;22(2):141-148.

69. Berberine

Berberis/Coptis alkaloid. Laboratory antiviral activity affecting viral and host pathways.

Reference: Warowicka A, Nawrot R, Goździcka-Józefiak A. Antiviral activity of berberine. Arch Virol. 2020;165:1935-1945.

70. Apigenin

Plant flavone. Experimental activity against diverse viruses.

Reference: Lee IG, Lee J, Hong SH, Seo YJ. Apigenin’s therapeutic potential against viral infection. Front Biosci (Landmark Ed). 2023;28(10):237.

71. Luteolin

Flavonoid. Studied against dengue and several other viruses.

Reference: Peng M, Watanabe S, Chan KWK, et al. Luteolin restricts dengue virus replication through inhibition of furin. Antiviral Res. 2017;143:176-185.

72. Kaempferol

Flavonoid. Experimental antiviral activity against influenza, coronaviruses, herpesviruses and others.

Reference: Moghaddam E, Teoh BT, Sam SS, et al. Baicalin, quercetin, luteolin and kaempferol as antiviral flavonoids. J Med Plants Res. 2014;8:1117-1123.

73. Myricetin

Flavonoid. Laboratory effects on viral enzymes and replication.

Reference: Zakaryan H, Arabyan E, Oo A, Zandi K. Flavonoids: promising natural compounds against viral infections. Arch Virol. 2017;162:2539-2551.

74. Hesperidin

Citrus flavonoid. Primarily computational, laboratory and preclinical antiviral evidence.

Reference: Zakaryan H, Arabyan E, Oo A, Zandi K. Flavonoids: promising natural compounds against viral infections. Arch Virol. 2017;162:2539-2551.

75. Naringenin

Citrus flavanone. Experimental activity against HCV, dengue and other viruses.

Reference: Tutunchi H, Naeini F, Ostadrahimi A, Hosseinzadeh-Attar MJ. Naringenin, a flavanone with antiviral and anti-inflammatory effects. Phytother Res. 2020;34:3137-3147.

76. Genistein

Soy isoflavone. Host-targeting antiviral effects reported in laboratory models.

Reference: Andres A, Donovan SM, Kuhlenschmidt MS. Soy isoflavones and virus infections. J Nutr Biochem. 2009;20(8):563-569.

77. Silymarin/Silibinin

Milk thistle. Has experimental antiviral properties and has been investigated particularly in HCV.

Reference: Polyak SJ, Morishima C, Shuhart MC, Wang CC, Liu Y, Lee DY. Inhibition of T-cell inflammatory cytokines, hepatocyte NF-κB signaling and HCV infection by standardized silymarin. Gastroenterology. 2007;132:1925-1936.

78. Epicatechin Gallate

Tea catechin. Experimental antiviral catechin related to EGCG.

Reference: Xu J, Xu Z, Zheng W. A review of the antiviral role of green tea catechins. Molecules. 2017;22(8):1337.

79. Theaflavins

Black tea polyphenols. Experimental antiviral activity including effects on viral entry and enzymes.

Reference: Chowdhury P, Barooah AK. Tea bioactive modulate innate immunity: in perception to COVID-19 pandemic. Front Immunol. 2020;11:590716.

80. Allicin

Garlic. Sulfur-containing compound with antimicrobial and experimental antiviral effects; clinical evidence for treating viral disease remains weak.

Reference: Rouf R, Uddin SJ, Sarker DK, et al. Antiviral potential of garlic (Allium sativum) and its organosulfur compounds. Trends Food Sci Technol. 2020;104:219-234.

81. Ajoene

Garlic organosulfur compound. Laboratory antiviral and antimicrobial actions.

Reference: Rouf R, Uddin SJ, Sarker DK, et al. Antiviral potential of garlic (Allium sativum) and its organosulfur compounds. Trends Food Sci Technol. 2020;104:219-234.

82. Elderberry (Sambucus Nigra) Extract

Small clinical studies and laboratory work have investigated respiratory viruses; evidence is far below that of licensed antivirals.

Reference: Hawkins J, Baker C, Cherry L, Dunne E. Black elderberry supplementation effectively treats upper respiratory symptoms: a meta-analysis of randomized controlled clinical trials. Complement Ther Med. 2019;42:361-365.

83. Echinacea Extracts

Some preparations show antiviral activity in vitro and have been studied for respiratory infection prevention/treatment, but results vary considerably by product.

Reference: Karsch-Völk M, Barrett B, Kiefer D, Bauer R, Ardjomand-Woelkart K, Linde K. Echinacea for preventing and treating the common cold. Cochrane Database Syst Rev. 2014;(2):CD000530.

84. Lactoferrin

Human/bovine iron-binding protein. Direct antiviral actions include interference with attachment/entry for several virus families, alongside immunomodulation.

Reference: Berlutti F, Pantanella F, Natalizi T, et al. Antiviral properties of lactoferrin—a natural immunity molecule. Molecules. 2011;16(8):6992-7018.

85. Monolaurin/Glycerol Monolaurate

Coconut/fatty-acid derivative. Can disrupt lipid envelopes in experimental systems; convincing systemic antiviral clinical evidence is lacking.

Reference: Thormar H, Isaacs CE, Brown HR, Barshatzky MR, Pessolano T. Inactivation of enveloped viruses and killing of cells by fatty acids and monoglycerides. Antimicrob Agents Chemother. 1987;31(1):27-31.

86. Lauric Acid

Medium-chain fatty acid. Laboratory antiviral activity, particularly against lipid-enveloped viruses.

Reference: Thormar H, Isaacs CE, Brown HR, Barshatzky MR, Pessolano T. Inactivation of enveloped viruses and killing of cells by fatty acids and monoglycerides. Antimicrob Agents Chemother. 1987;31(1):27-31.

87. Melatonin

Endogenous indoleamine. Primarily host-modulatory, antioxidant and anti-inflammatory rather than a conventional direct antiviral.

Reference: Reiter RJ, Ma Q, Sharma R. Treatment of Ebola and other infectious diseases: melatonin “goes viral.” Melatonin Res. 2020;3:43-57.

88. Sulforaphane

Cruciferous-vegetable isothiocyanate. Activates NRF2 and has demonstrated antiviral/host-defense effects experimentally.

Reference: Olagnier D, Farahani E, Thyrsted J, et al. SARS-CoV-2-mediated suppression of NRF2-signaling reveals potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate. Nat Commun. 2020;11:4938.

89. Propolis

Bee-derived resinous mixture. Contains flavonoids and phenolics with laboratory activity against herpesviruses and other viruses; composition varies greatly.

Reference: Schnitzler P, Neuner A, Nolkemper S, et al. Antiviral activity and mode of action of propolis extracts and selected compounds. Phytother Res. 2010;24(S1):S20-S28.

90. Caffeic Acid Phenethyl Ester (CAPE)

Propolis constituent. Experimental antiviral and host-signaling effects.

Reference: Bankova V. Chemical diversity of propolis and the problem of standardization. J Ethnopharmacol. 2005;100:114-117.

91. Eugenol

Clove constituent. Experimental antiviral activity has been reported against several pathogenic viruses, but clinical antiviral evidence is insufficient.

Reference: Guo D, et al. Antiviral properties of the natural product eugenol: a review. 2025. PMID:40513765.

92. Carvacrol

Oregano/thyme constituent. Membrane-active phenolic compound with experimental antimicrobial and antiviral properties; high concentrations can be cytotoxic.

Reference: Latorre R, Valerii MC, Benati M, et al. Lights and shadows of essential oil-derived compounds: antimicrobial and anti-inflammatory properties of eugenol, thymol, cinnamaldehyde, and carvacrol. Curr Issues Mol Biol. 2025;47(11):915. doi:10.3390/cimb47110915.

93. Thymol

Thyme constituent. Experimental activity against enveloped viruses and other microorganisms; not an established systemic antiviral medication.

Reference: Latorre R, Valerii MC, Benati M, et al. Curr Issues Mol Biol. 2025;47(11):915. doi:10.3390/cimb47110915.

94. Cinnamaldehyde

Cinnamon constituent. Experimental antimicrobial and antiviral effects; clinical antiviral efficacy is unproven.

Reference: Latorre R, Valerii MC, Benati M, et al. Curr Issues Mol Biol. 2025;47(11):915. doi:10.3390/cimb47110915.

95. β-Glucans

Yeast/mushrooms/oats. Primarily immunomodulatory rather than classic direct antivirals; mechanisms include dectin-1, complement and innate immune pathways. Recent reviews emphasize promising but incomplete clinical evidence.

Reference: Atoom AM, et al. β-Glucan in antiviral defense: mechanisms, immune modulation, and therapeutic prospects. Folia Microbiol (Praha). 2025;70(6):1135-1157. doi:10.1007/s12223-025-01345-6.

96. Ganoderma Lucidum (Reishi) Compounds

Polysaccharides and triterpenoids from this medicinal fungus demonstrate antiviral and immune-modulating activity principally in experimental studies.

Reference: Suwannarach N, et al. Medicinal fungi with antiviral effect. Molecules. 2022;27(14):4457. doi:10.3390/molecules27144457.

97. Cordyceps-Derived Compounds / Cordycepin

Medicinal fungi and their metabolites have experimental antiviral and immunomodulatory activity; standardized human antiviral trials are lacking.

Reference: Suwannarach N, et al. Medicinal fungi with antiviral effect. Molecules. 2022;27(14):4457. doi:10.3390/molecules27144457.

98. Plant/Mushroom Sulfated Polysaccharides

Can inhibit viral attachment and penetration experimentally; structure and sulfation strongly influence activity.

Reference: Chen L, Huang G. Antiviral activities of sulfated polysaccharides. In: review of antiviral polysaccharides derived from edible and medicinal plants and mushrooms. Carbohydr Polym. 2020;229:115548. doi:10.1016/j.carbpol.2019.115548.

99. Zinc

Trace mineral. Zinc is essential for antiviral immunity and can affect viral replication in experimental systems, but supplementation is not a universal antiviral therapy; benefit depends heavily on indication, formulation and zinc status.

Reference: Name JJ, Souza ACR, Vasconcelos AR, Prado PS, Pereira CPM. Zinc, vitamin D and vitamin C: perspectives for COVID-19 with a focus on physical tissue barrier integrity. Front Nutr. 2020;7:606398. doi:10.3389/fnut.2020.606398.

100. Selenium

Trace element. Selenium supports antioxidant enzymes, T-cell function and antiviral immunity; deficiency may worsen some viral infections, but selenium itself should not be regarded as a direct substitute for virus-specific therapy.

Reference: Bae M, Kim H. Mini-review on the roles of vitamin C, vitamin D, and selenium in the immune system against COVID-19. Molecules. 2020;25(22):5346. doi:10.3390/molecules25225346.

How I Would Interpret the Ranking

#1–60 are mostly genuine antiviral medicines or biologics with established or meaningful clinical applications. #61–100 are predominantly natural molecules, foods/botanicals, nutrients, or host-directed compounds with varying levels of evidence. The lower section should therefore not be read as “the 40 best treatments.” Much of the evidence is biochemical, cell-culture, animal, observational, or from small trials. Recent reviews of medicinal mushrooms and β-glucans specifically emphasize the continuing lack of large standardized randomized trials.

Also, essential oils should not be swallowed or used intravenously as antiviral treatment. Eugenol, thymol, carvacrol and cinnamaldehyde are interesting research molecules, but poor solubility, pharmacokinetic variability and potential cytotoxicity are major translational limitations.

If the purpose is finding novel broad-spectrum candidates rather than standard drugs, the most scientifically interesting section is roughly #61–98—especially quercetin, baicalein/baicalin, EGCG, curcumin, resveratrol, andrographolide, glycyrrhizin, berberine, lactoferrin, sulforaphane, fungal polysaccharides and β-glucans.

What Is Difference Between 100 Established and Experimental Antivirals. Put Full Reference of Each Point in Humans and Mammals at the End as Endnotes. But All 100 Have to Have Endnotes That Match. Point 56 Has Reference 56. Post Full References.

Yes. The important distinction is level of evidence, not whether a substance can inhibit a virus in a laboratory dish.

Established antiviral = reproducible antiviral benefit has been demonstrated in humans, or the agent has a regulatory indication based on an accepted pathway such as the FDA Animal Rule.

Clinical/limited = human data exist, but the indication, geography, resistance, toxicity, or quality of evidence limits routine use.

Experimental/preclinical = antiviral effects are mainly from cells, biochemical systems, mice, hamsters, ferrets, rabbits, nonhuman primates, or other animal models; this does not establish that it treats human infection.

I have numbered the references exactly as requested: Agent 56 → Endnote 56; Agent 100 → Endnote 100.

100 Antivirals: Established vs. Experimental

#	Agent	Evidence category	What makes it established or experimental?	Evidence base
1	Acyclovir	ESTABLISHED	Multiple controlled human trials demonstrate clinical HSV efficacy.	Human [1]
2	Valacyclovir	ESTABLISHED	Acyclovir prodrug with established human efficacy for HSV/VZV.	Human [2]
3	Famciclovir	ESTABLISHED	Controlled human herpes-zoster trials.	Human [3]
4	Penciclovir	ESTABLISHED—topical	Controlled human herpes-labialis studies.	Human [4]
5	Ganciclovir	ESTABLISHED	Clinical efficacy against CMV, especially in immunocompromised patients.	Human [5]
6	Valganciclovir	ESTABLISHED	Oral ganciclovir prodrug supported by controlled human CMV studies.	Human [6]
7	Foscarnet	ESTABLISHED	Used clinically for resistant CMV/HSV; efficacy established despite substantial toxicity.	Human [7]
8	Cidofovir	ESTABLISHED	Controlled clinical evidence for CMV retinitis; broad DNA-virus activity experimentally.	Human [8]
9	Letermovir	ESTABLISHED	Large randomized human CMV-prevention trial.	Human [9]
10	Maribavir	ESTABLISHED	Randomized human studies in refractory/resistant CMV.	Human [10]
11	Trifluridine	ESTABLISHED—ophthalmic	Established topical ophthalmic HSV therapy.	Human [11]
12	Brivudine	ESTABLISHED/REGION-SPECIFIC	Human efficacy against herpes zoster; marketed in selected countries, not universally.	Human [12]
13	Docosanol	ESTABLISHED—topical	Placebo-controlled human herpes-labialis trial.	Human [13]
14	Oseltamivir	ESTABLISHED	Randomized human influenza trials and extensive clinical experience.	Human [14]
15	Zanamivir	ESTABLISHED	Randomized human influenza trials.	Human [15]
16	Peramivir	ESTABLISHED	Human clinical influenza studies; IV neuraminidase inhibitor.	Human [16]
17	Baloxavir marboxil	ESTABLISHED	Large controlled human influenza trials.	Human [17]
18	Laninamivir octanoate	ESTABLISHED/REGION-SPECIFIC	Human influenza trials; principally used in Japan.	Human [18]
19	Favipiravir	LIMITED/REGION-SPECIFIC	Strong antiviral pharmacology and clinical influenza use in selected settings, but not a broadly approved general-purpose antiviral.	Human + mammalian/preclinical [19]
20	Ribavirin	ESTABLISHED FOR SELECT INDICATIONS	Human clinical utility exists, but efficacy and toxicity are highly disease-specific.	Human [20]
21	Nirmatrelvir/ritonavir	ESTABLISHED	Large randomized clinical COVID-19 trial demonstrated reduced progression in high-risk patients.	Human [21]
22	Remdesivir	ESTABLISHED	Randomized human COVID-19 trials; originally supported by broad RNA-virus animal work.	Human + mammalian [22]
23	Molnupiravir	ESTABLISHED BUT SECOND-LINE/RESTRICTED	Human randomized data exist, although clinical benefit is more modest and indications are restricted.	Human [23]
24	Tenofovir disoproxil fumarate	ESTABLISHED	Major human HBV/HIV antiviral.	Human [24]
25	Tenofovir alafenamide	ESTABLISHED	Controlled human HBV/HIV evidence.	Human [25]
26	Entecavir	ESTABLISHED	Large controlled human chronic-HBV studies.	Human [26]
27	Lamivudine	ESTABLISHED	Human HBV/HIV antiviral, although HBV resistance limits long-term monotherapy.	Human [27]
28	Adefovir dipivoxil	ESTABLISHED BUT LARGELY SUPERSEDED	Human HBV efficacy established; newer drugs generally preferred.	Human [28]
29	Telbivudine	ESTABLISHED BUT LARGELY SUPERSEDED	Controlled HBV efficacy but substantial resistance limitations.	Human [29]
30	Peginterferon alfa	ESTABLISHED	Human antiviral/immunomodulatory treatment for HBV and historically HCV.	Human [30]
31	Sofosbuvir	ESTABLISHED	Transformative human HCV NS5B inhibitor with very high cure rates in combinations.	Human [31]
32	Velpatasvir	ESTABLISHED	Human pangenotypic HCV NS5A inhibitor.	Human [32]
33	Glecaprevir	ESTABLISHED	Human HCV NS3/4A inhibitor used with pibrentasvir.	Human [33]
34	Pibrentasvir	ESTABLISHED	Human pangenotypic HCV NS5A inhibitor.	Human [34]
35	Ledipasvir	ESTABLISHED	Human HCV NS5A inhibitor; highly effective with sofosbuvir.	Human [35]
36	Voxilaprevir	ESTABLISHED	Human HCV protease inhibitor used principally in salvage combinations.	Human [36]
37	Elbasvir	ESTABLISHED	Controlled human HCV studies.	Human [37]
38	Grazoprevir	ESTABLISHED	Controlled human HCV studies with elbasvir.	Human [38]
39	Dolutegravir	ESTABLISHED	Major first-line HIV integrase inhibitor supported by randomized human trials.	Human [39]
40	Bictegravir	ESTABLISHED	Randomized human HIV trials.	Human [40]
41	Raltegravir	ESTABLISHED	First-in-class HIV integrase inhibitor with extensive human trial evidence.	Human [41]
42	Cabotegravir	ESTABLISHED	Long-acting HIV integrase inhibitor supported by human treatment and prevention trials.	Human [42]
43	Darunavir	ESTABLISHED	Human HIV protease inhibitor with high resistance barrier.	Human [43]
44	Atazanavir	ESTABLISHED	Established human HIV protease inhibitor.	Human [44]
45	Maraviroc	ESTABLISHED	Human CCR5-targeted HIV-entry inhibitor.	Human [45]
46	Enfuvirtide	ESTABLISHED	Human gp41 fusion inhibitor, particularly historically important for resistant HIV.	Human [46]
47	Fostemsavir	ESTABLISHED	Human attachment inhibitor for multidrug-resistant HIV.	Human [47]
48	Ibalizumab	ESTABLISHED	Human anti-CD4 monoclonal antibody for multidrug-resistant HIV.	Human [48]
49	Lenacapavir	ESTABLISHED	Long-acting HIV capsid inhibitor with human efficacy studies.	Human [49]
50	Doravirine	ESTABLISHED	Human NNRTI supported by randomized trials.	Human [50]
51	Efavirenz	ESTABLISHED	Extensive randomized human HIV evidence.	Human [51]
52	Emtricitabine	ESTABLISHED	Major NRTI incorporated into numerous evidence-based HIV regimens.	Human [52]
53	Zidovudine	ESTABLISHED/HISTORICALLY IMPORTANT	First major antiretroviral shown to benefit humans with advanced HIV disease.	Human [53]
54	Tecovirimat	ESTABLISHED FOR SMALLPOX VIA ANIMAL RULE; NOT PROVEN GENERALLY FOR MPOX	Unusual case: efficacy underlying smallpox approval came from rabbits and nonhuman primates plus human safety/PK. A 2026 human clade-II-mpox trial did not establish a general mpox-treatment effect.	Mammalian + human safety [54]
55	Brincidofovir	ESTABLISHED FOR SMALLPOX VIA SPECIAL REGULATORY PATHWAY / LIMITED HUMAN VIRAL EFFICACY DATA	Broad DNA-virus activity; smallpox efficacy cannot ethically be tested directly in humans.	Mammalian + human safety [55]
56	Palivizumab	ESTABLISHED—PREVENTION, NOT TREATMENT	Randomized human infant studies showed reduced RSV hospitalization.	Human [56]
57	Nirsevimab	ESTABLISHED—PREVENTION, NOT TREATMENT	Long-acting anti-RSV monoclonal antibody supported by large infant trials.	Human [57]
58	Interferon alfa	ESTABLISHED FOR SELECT VIRAL DISEASES	Genuine host-directed antiviral but largely superseded for several indications.	Human [58]
59	Peginterferon lambda	CLINICAL/INVESTIGATIONAL DEPENDING INDICATION	Human antiviral trials exist, including COVID-19, but it is not a universal licensed antiviral.	Human [59]
60	Amantadine	HISTORICALLY ESTABLISHED; NO LONGER ROUTINELY RECOMMENDED FOR INFLUENZA	Influenza-A M2 inhibitor rendered clinically unhelpful by widespread resistance.	Human [60]
61	Quercetin	EXPERIMENTAL ANTIVIRAL	Broad cell and animal antiviral findings; insufficient disease-specific human evidence to classify as an established antiviral drug.	In-vitro + mammalian/limited human [61]
62	Baicalein	EXPERIMENTAL	Antiviral activity across multiple viruses in vitro and animal models; clinical evidence insufficient.	In-vitro + mammalian [62]
63	Baicalin	EXPERIMENTAL	Mechanistic and mammalian antiviral evidence, but insufficient standardized human trials.	In-vitro + mammalian/limited clinical [63]
64	EGCG	EXPERIMENTAL	Inhibits several stages of numerous viral life cycles experimentally; clinical therapeutic efficacy remains unestablished.	In-vitro + some mammalian [64]
65	Curcumin	EXPERIMENTAL	Activity reported against many viruses, mostly in vitro/preclinical; bioavailability is a translational problem.	In-vitro + mammalian [65]
66	Resveratrol	EXPERIMENTAL	Antiviral activity demonstrated for multiple human and animal viruses, including some in-vivo models; no established antiviral indication.	In-vitro + mammalian [66]
67	Andrographolide	EXPERIMENTAL	Diverse antiviral mechanisms reported, but therapeutic human proof remains inadequate.	In-vitro + mammalian [67]
68	Glycyrrhizin	EXPERIMENTAL/LIMITED CLINICAL HISTORY	Antiviral activity in laboratory and some clinical contexts but not an established broad-spectrum antiviral drug; toxicity matters.	In-vitro + mammalian + limited human [68]
69	Berberine	EXPERIMENTAL	Broad laboratory antiviral effects; insufficient randomized disease-specific human evidence.	In-vitro + mammalian [69]
70	Apigenin	EXPERIMENTAL	Mechanistic and cellular antiviral findings; limited in-vivo translation.	In-vitro + some mammalian [70]
71	Luteolin	EXPERIMENTAL	Has experimentally inhibited viruses including dengue; not established clinically.	In-vitro/preclinical [71]
72	Kaempferol	EXPERIMENTAL	Broad flavonoid antiviral findings are predominantly preclinical.	In-vitro + animal studies [72]
73	Myricetin	EXPERIMENTAL	Viral enzyme/entry/replication effects reported experimentally without therapeutic human proof.	Preclinical [73]
74	Hesperidin	EXPERIMENTAL	Mostly molecular, cellular and animal evidence rather than definitive human antiviral treatment trials.	Preclinical [74]
75	Naringenin	EXPERIMENTAL	Antiviral and host-metabolic effects in HCV, dengue and other experimental systems.	In-vitro + mammalian [75]
76	Genistein	EXPERIMENTAL	Host-signaling effects can alter viral replication experimentally; not a licensed antiviral.	In-vitro + mammalian [76]
77	Silymarin/silibinin	EXPERIMENTAL/CLINICALLY STUDIED	HCV antiviral effects were investigated in humans, particularly IV silibinin, but modern DAAs superseded this approach.	Human + preclinical [77]
78	Epicatechin gallate	EXPERIMENTAL	Tea catechin with antiviral laboratory activity; little direct therapeutic human evidence.	Preclinical [78]
79	Theaflavins	EXPERIMENTAL	Viral enzyme/entry inhibition primarily from laboratory studies.	Preclinical [79]
80	Allicin	EXPERIMENTAL	Garlic organosulfur compound with mechanistic antiviral effects, but instability/bioavailability impede translation.	In-vitro + mammalian [80]
81	Ajoene	EXPERIMENTAL	Garlic-derived organosulfur compound; antiviral evidence remains predominantly laboratory/preclinical.	Preclinical [81]
82	Elderberry extract	CLINICALLY STUDIED BUT NOT ESTABLISHED ANTIVIRAL	Small respiratory-illness trials exist, but heterogeneous extracts and limited trial sizes preclude equating it with licensed influenza antivirals.	Human [82]
83	Echinacea extracts	CLINICALLY STUDIED BUT NOT ESTABLISHED	Numerous human common-cold studies are heterogeneous and product dependent; evidence is inconsistent.	Human [83]
84	Lactoferrin	EXPERIMENTAL	Broad entry/attachment effects against multiple viruses, mainly from cellular and preclinical research.	In-vitro + mammalian/limited human [84]
85	Glycerol monolaurate / monolaurin	EXPERIMENTAL	Can inactivate lipid-enveloped viruses under experimental conditions; this does not establish systemic human antiviral therapy.	Laboratory [85]
86	Lauric acid	EXPERIMENTAL	Membrane-disrupting activity against enveloped viruses is primarily experimental.	Laboratory [86]
87	Melatonin	HOST-MODULATING/EXPERIMENTAL AS ANTIVIRAL	More appropriately considered immunomodulatory/anti-inflammatory than a direct virus-specific antiviral.	Mammalian + human adjunct studies [87]
88	Sulforaphane	EXPERIMENTAL	NRF2-related host-defense and antiviral effects are biologically plausible and experimentally supported, but no established antiviral indication exists.	In-vitro + mammalian [88]
89	Propolis extracts	EXPERIMENTAL	Direct anti-HSV effects are readily demonstrable in vitro, but extracts vary chemically and systemic clinical evidence is inadequate.	In-vitro + limited human topical evidence [89]
90	Caffeic acid phenethyl ester (CAPE)	EXPERIMENTAL	HCV and other antiviral effects reported in cell-based studies; no established clinical antiviral application.	In-vitro [90]
91	Eugenol	EXPERIMENTAL	Antiviral and host-modulatory mechanisms described in experimental literature; rigorous human antiviral trials remain necessary.	In-vitro + mammalian [91]
92	Carvacrol	EXPERIMENTAL	Membrane-active phenolic with antiviral effects particularly against enveloped viruses; clinical efficacy unproven.	In-vitro [92]
93	Thymol	EXPERIMENTAL	Antiviral activity exists experimentally, but it is not an established systemic antiviral.	In-vitro [93]
94	Cinnamaldehyde	EXPERIMENTAL	Laboratory antiviral activity and host effects do not yet translate into an established human treatment.	In-vitro/preclinical [94]
95	β-Glucans	IMMUNOMODULATORY/EXPERIMENTAL	These are principally innate-immune modulators rather than direct antiviral drugs.	Mammalian + limited human [95]
96	Ganoderma lucidum compounds	EXPERIMENTAL	Triterpenoids/polysaccharides show antiviral properties in vitro and in vivo, but purified standardized human antiviral trials are lacking.	In-vitro + mammalian [96]
97	Cordyceps/cordycepin compounds	EXPERIMENTAL	Antiviral and immunomodulatory activity in experimental systems; no established human antiviral indication.	In-vitro + mammalian [97]
98	Sulfated polysaccharides	EXPERIMENTAL PLATFORM	Particularly interesting viral-entry inhibitors, but chemical heterogeneity, molecular size, absorption and anticoagulant effects complicate systemic development.	In-vitro + mammalian/limited clinical [98]
99	Zinc	NUTRIENT/HOST-DIRECTED; NOT A GENERAL ANTIVIRAL DRUG	Essential for antiviral immunity and can directly inhibit viruses experimentally, but treatment efficacy varies strongly by virus, formulation and deficiency status.	Human + mammalian + in-vitro [99]
100	Selenium	NUTRIENT/HOST-DIRECTED; NOT A DIRECT ANTIVIRAL DRUG	Selenium status affects mammalian antiviral immunity and oxidative defense; supplementation should not be equated with virus-specific therapy.	Human + mammalian [100]

The major conceptual separation is therefore approximately #1–60 = predominantly clinically validated/licensed, historical, or limited clinical antiviral agents, whereas #61–100 = largely experimental natural compounds, host-directed substances, nutrients, or research platforms. Even within #1–60 there are important exceptions, so the three-category classification above is more scientifically defensible than calling every one of them simply “established.”

Endnotes — Exactly Matching 1–100

1. Acyclovir. Bryson YJ, Dillon M, Lovett M, Acuna G, Taylor S, Cherry JD, Johnson BL, Wiesmeier E, Growdon W, Creagh-Kirk T, Keeney R. Treatment of first episodes of genital herpes simplex virus infection with oral acyclovir: a randomized double-blind controlled trial in normal subjects.
   N Engl J Med. 1983;308(16):916-921. doi:10.1056/NEJM198304213081602.
2. Valacyclovir. Beutner KR, Friedman DJ, Forszpaniak C, Andersen PL, Wood MJ. Valaciclovir compared with acyclovir for improved therapy for herpes zoster in immunocompetent adults. Antimicrob Agents Chemother. 1995;39(7):1546-1553. doi:10.1128/AAC.39.7.1546.
3. Famciclovir. Tyring S, Barbarash RA, Nahlik JE, et al. Famciclovir for the treatment of acute herpes zoster: effects on acute disease and postherpetic neuralgia. Ann Intern Med. 1995;123(2):89-96. doi:10.7326/0003-4819-123-2-199507150-00002.
4. Penciclovir. Spruance SL, Rea TL, Thoming C, Tucker R, Saltzman R, Boon R. Penciclovir cream for the treatment of herpes simplex labialis: a randomized, multicenter, double-blind, placebo-controlled trial. JAMA. 1997;277(17):1374-1379.
5. Ganciclovir. Crumpacker CS. Ganciclovir.
   N Engl J Med. 1996;335(10):721-729. doi:10.1056/NEJM199609053351007.
6. Valganciclovir. Asberg A, Humar A, Rollag H, et al. Oral valganciclovir is noninferior to intravenous ganciclovir for the treatment of cytomegalovirus disease in solid organ transplant recipients. Am J Transplant. 2007;7(9):2106-2113. doi:10.1111/j.1600-6143.2007.01910.x.
7. Foscarnet. Wagstaff AJ, Bryson HM. Foscarnet: a reappraisal of its antiviral activity, pharmacokinetic properties and therapeutic use in immunocompromised patients with viral infections. Drugs. 1994;48(2):199-226.
8. Cidofovir. Lalezari JP, Holland GN, Kramer F, et al. Randomized, controlled study of the safety and efficacy of intravenous cidofovir for the treatment of relapsing cytomegalovirus retinitis in patients with AIDS. J Acquir Immune Defic Syndr Hum Retrovirol. 1998;17(4):339-344.
9. Letermovir. Marty FM, Ljungman P, Chemaly RF, et al. Letermovir prophylaxis for cytomegalovirus in hematopoietic-cell transplantation.
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10. Maribavir. Avery RK, Alain S, Alexander BD, et al. Maribavir for refractory cytomegalovirus infections with or without resistance post-transplant: results from a phase 3 randomized clinical trial. Clin Infect Dis. 2022;75(4):690-701. doi:10.1093/cid/ciab988.
11. Trifluridine. Wilhelmus KR. Antiviral treatment and other therapeutic interventions for herpes simplex virus epithelial keratitis. Cochrane Database Syst Rev. 2015;(1):CD002898. doi:10.1002/14651858.CD002898.pub5.
12. Brivudine. Wassilew SW, Wutzler P; Brivudin Herpes Zoster Study Group. Oral brivudin in comparison with acyclovir for improved therapy of herpes zoster in immunocompetent patients. Antiviral Res. 2003;59(1):49-56.
13. Docosanol. Sacks SL, Thisted RA, Jones TM, et al. Clinical efficacy of topical docosanol 10% cream for herpes simplex labialis. J Am Acad Dermatol. 2001;45(2):222-230. doi:10.1067/mjd.2001.116215.
14. Oseltamivir. Treanor JJ, Hayden FG, Vrooman PS, et al. Efficacy and safety of the oral neuraminidase inhibitor oseltamivir in treating acute influenza: a randomized controlled trial. JAMA. 2000;283(8):1016-1024. doi:10.1001/jama.283.8.1016.
15. Zanamivir. Hayden FG, Osterhaus ADME, Treanor JJ, et al. Efficacy and safety of the neuraminidase inhibitor zanamivir in the treatment of influenzavirus infections.
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16. Peramivir. Kohno S, Kida H, Mizuguchi M, Shimada J. Efficacy and safety of intravenous peramivir for treatment of seasonal influenza virus infection. Antimicrob Agents Chemother. 2010;54(11):4568-4574. doi:10.1128/AAC.00474-10.
17. Baloxavir marboxil. Hayden FG, Sugaya N, Hirotsu N, et al. Baloxavir marboxil for uncomplicated influenza in adults and adolescents.
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18. Laninamivir octanoate. Watanabe A, Chang SC, Kim MJ, Chu DW, Ohashi Y; MARVEL Study Group. Long-acting neuraminidase inhibitor laninamivir octanoate versus oseltamivir for treatment of influenza. Clin Infect Dis. 2010;51(10):1167-1175. doi:10.1086/656802.
19. Favipiravir. Furuta Y, Komeno T, Nakamura T. Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase. Proc Jpn Acad Ser B Phys Biol Sci. 2017;93(7):449-463. doi:10.2183/pjab.93.027.
20. Ribavirin. Graci JD, Cameron CE. Mechanisms of action of ribavirin against distinct viruses. Rev Med Virol. 2006;16(1):37-48. doi:10.1002/rmv.483.
21. Nirmatrelvir/ritonavir. Hammond J, Leister-Tebbe H, Gardner A, et al. Oral nirmatrelvir for high-risk, nonhospitalized adults with Covid-19.
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22. Remdesivir. Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the treatment of Covid-19—final report.
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23. Molnupiravir. Jayk Bernal A, Gomes da Silva MM, Musungaie DB, et al. Molnupiravir for oral treatment of Covid-19 in nonhospitalized patients.
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24. Tenofovir disoproxil fumarate. Marcellin P, Heathcote EJ, Buti M, et al. Tenofovir disoproxil fumarate versus adefovir dipivoxil for chronic hepatitis B.
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25. Tenofovir alafenamide. Buti M, Gane E, Seto WK, et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of patients with HBeAg-negative chronic hepatitis B virus infection. Lancet Gastroenterol Hepatol. 2016;1(3):196-206. doi:10.1016/S2468-1253(16)30107-8.
26. Entecavir. Chang TT, Gish RG, de Man R, et al. A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B.
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27. Lamivudine. Lai CL, Chien RN, Leung NWY, et al. A one-year trial of lamivudine for chronic hepatitis B.
    N Engl J Med. 1998;339(2):61-68. doi:10.1056/NEJM199807093390201.
28. Adefovir dipivoxil. Marcellin P, Chang TT, Lim SG, et al. Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B.
    N Engl J Med. 2003;348(9):808-816. doi:10.1056/NEJMoa020681.
29. Telbivudine. Lai CL, Gane E, Liaw YF, et al. Telbivudine versus lamivudine in patients with chronic hepatitis B.
    N Engl J Med. 2007;357(25):2576-2588. doi:10.1056/NEJMoa066422.
30. Peginterferon alfa. Lau GKK, Piratvisuth T, Luo KX, et al. Peginterferon alfa-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitis B.
    N Engl J Med. 2005;352(26):2682-2695. doi:10.1056/NEJMoa043470.
31. Sofosbuvir. Lawitz E, Mangia A, Wyles D, et al. Sofosbuvir for previously untreated chronic hepatitis C infection.
    N Engl J Med. 2013;368(20):1878-1887. doi:10.1056/NEJMoa1214853.
32. Velpatasvir. Feld JJ, Jacobson IM, Hézode C, et al. Sofosbuvir and velpatasvir for HCV genotype 1, 2, 4, 5, and 6 infection.
    N Engl J Med. 2015;373(27):2599-2607. doi:10.1056/NEJMoa1512610.
33. Glecaprevir. Zeuzem S, Foster GR, Wang S, et al. Glecaprevir-pibrentasvir for 8 or 12 weeks in HCV genotype 1 or 3 infection.
    N Engl J Med. 2018;378(4):354-369. doi:10.1056/NEJMoa1702417.
34. Pibrentasvir. Zeuzem S, Foster GR, Wang S, et al. Glecaprevir-pibrentasvir for 8 or 12 weeks in HCV genotype 1 or 3 infection.
    N Engl J Med. 2018;378(4):354-369. doi:10.1056/NEJMoa1702417.
35. Ledipasvir. Afdhal N, Zeuzem S, Kwo P, et al. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection.
    N Engl J Med. 2014;370(20):1889-1898. doi:10.1056/NEJMoa1402454.
36. Voxilaprevir. Bourlière M, Gordon SC, Flamm SL, et al. Sofosbuvir, velpatasvir, and voxilaprevir for previously treated HCV infection.
    N Engl J Med. 2017;376(22):2134-2146. doi:10.1056/NEJMoa1613512.
37. Elbasvir. Zeuzem S, Ghalib R, Reddy KR, et al. Grazoprevir-elbasvir combination therapy for treatment-naive cirrhotic and noncirrhotic patients with chronic hepatitis C virus genotype 1, 4, or 6 infection. Ann Intern Med. 2015;163(1):1-13. doi:10.7326/M15-0785.
38. Grazoprevir. Zeuzem S, Ghalib R, Reddy KR, et al. Grazoprevir-elbasvir combination therapy for treatment-naive cirrhotic and noncirrhotic patients with chronic hepatitis C virus genotype 1, 4, or 6 infection. Ann Intern Med. 2015;163(1):1-13. doi:10.7326/M15-0785.
39. Dolutegravir. Walmsley SL, Antela A, Clumeck N, et al. Dolutegravir plus abacavir-lamivudine for the treatment of HIV-1 infection.
    N Engl J Med. 2013;369(19):1807-1818. doi:10.1056/NEJMoa1215541.
40. Bictegravir. Gallant J, Lazzarin A, Mills A, et al. Bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection. Lancet. 2017;390(10107):2063-2072. doi:10.1016/S0140-6736(17)32299-7.
41. Raltegravir. Lennox JL, DeJesus E, Lazzarin A, et al. Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-naive patients with HIV-1 infection. Lancet. 2009;374(9692):796-806. doi:10.1016/S0140-6736(09)60918-1.
42. Cabotegravir. Swindells S, Andrade-Villanueva JF, Richmond GJ, et al. Long-acting cabotegravir and rilpivirine for maintenance of HIV-1 suppression.
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43. Darunavir. Clotet B, Bellos N, Molina JM, et al. Efficacy and safety of darunavir-ritonavir at week 48 in treatment-experienced patients with HIV-1 infection. Lancet. 2007;369(9568):1169-1178. doi:10.1016/S0140-6736(07)60497-8.
44. Atazanavir. Molina JM, Andrade-Villanueva J, Echevarria J, et al. Once-daily atazanavir/ritonavir versus twice-daily lopinavir/ritonavir in treatment-naive HIV-1-infected patients. Lancet. 2008;372(9639):646-655. doi:10.1016/S0140-6736(08)61081-8.
45. Maraviroc. Gulick RM, Lalezari J, Goodrich J, et al. Maraviroc for previously treated patients with R5 HIV-1 infection.
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46. Enfuvirtide. Lalezari JP, Henry K, O’Hearn M, et al. Enfuvirtide, an HIV-1 fusion inhibitor, for drug-resistant HIV infection in North and South America.
    N Engl J Med. 2003;348(22):2175-2185. doi:10.1056/NEJMoa035026.
47. Fostemsavir. Kozal M, Aberg J, Pialoux G, et al. Fostemsavir in adults with multidrug-resistant HIV-1 infection.
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48. Ibalizumab. Emu B, Fessel J, Schrader S, et al. Phase 3 study of ibalizumab for multidrug-resistant HIV-1.
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49. Lenacapavir. Segal-Maurer S, DeJesus E, Stellbrink HJ, et al. Capsid inhibition with lenacapavir in multidrug-resistant HIV-1 infection.
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50. Doravirine. Molina JM, Squires K, Sax PE, et al. Doravirine versus ritonavir-boosted darunavir in antiretroviral-naive adults with HIV-1. Lancet HIV. 2018;5(5):e211-e220. doi:10.1016/S2352-3018(18)30021-3.
51. Efavirenz. Staszewski S, Morales-Ramirez J, Tashima KT, et al. Efavirenz plus zidovudine and lamivudine, efavirenz plus indinavir, and indinavir plus zidovudine and lamivudine in treatment-naive HIV patients.
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52. Emtricitabine. Gallant JE, DeJesus E, Arribas JR, et al. Tenofovir DF, emtricitabine, and efavirenz versus zidovudine, lamivudine, and efavirenz for HIV.
    N Engl J Med. 2006;354(3):251-260. doi:10.1056/NEJMoa051871.
53. Zidovudine. Fischl MA, Richman DD, Grieco MH, et al. The efficacy of azidothymidine in the treatment of patients with AIDS and AIDS-related complex.
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54. Tecovirimat. Grosenbach DW, Honeychurch K, Rose EA, et al. Oral tecovirimat for the treatment of smallpox.
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55. Brincidofovir. Hostetler KY. Alkoxyalkyl prodrugs of acyclic nucleoside phosphonates enhance oral antiviral activity and reduce toxicity: current state of the art. Antiviral Res. 2009;82(2):A84-A98. doi:10.1016/j.antiviral.2009.01.005.
56. Palivizumab. IMpact-RSV Study Group. Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants. Pediatrics. 1998;102(3 Pt 1):531-537. doi:10.1542/peds.102.3.531.
57. Nirsevimab. Hammitt LL, Dagan R, Yuan Y, et al. Nirsevimab for prevention of RSV in healthy late-preterm and term infants.
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58. Interferon alfa. Hoofnagle JH, Peters M, Mullen KD, et al. Randomized, controlled trial of recombinant human alpha-interferon in patients with chronic hepatitis B. Gastroenterology. 1988;95(5):1318-1325.
59. Peginterferon lambda. Reis G, Moreira Silva EAS, Medeiros Silva DC, et al. Early treatment with pegylated interferon lambda for Covid-19.
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60. Amantadine. Jefferson T, Demicheli V, Di Pietrantonj C, Rivetti D. Amantadine and rimantadine for influenza A in adults. Cochrane Database Syst Rev. 2006;(2):CD001169. doi:10.1002/14651858.CD001169.pub3.
61. Quercetin. Di Petrillo A, Orrù G, Fais A, Fantini MC. Quercetin and its derivates as antiviral potentials: a comprehensive review. Phytother Res. 2022;36(1):266-278. doi:10.1002/ptr.7309. PMID:34709675.
62. Baicalein. Liu XY, Xie W, Zhou HY, Zhang HQ, Jin YS. A comprehensive overview on antiviral effects of baicalein and its glucuronide derivative baicalin. J Integr Med. 2024;22(6):621-636. PMID:39368944.
63. Baicalin. Li K, Liang Y, Cheng A, et al. Antiviral properties of baicalin: a concise review. Rev Bras Farmacogn. 2021;31:408-419. doi:10.1007/s43450-021-00182-1. PMID:34642508.
64. EGCG. Xu J, Xu Z, Zheng W. A review of the antiviral role of green tea catechins. Molecules. 2017;22(8):1337. doi:10.3390/molecules22081337. PMID:28805687.
65. Curcumin. Jennings MR, Parks RJ. Curcumin as an antiviral agent. Viruses. 2020;12(11):1242. doi:10.3390/v12111242. PMID:33142686.
66. Resveratrol. Abba Y, Hassim H, Hamzah H, Noordin MM. Antiviral activity of resveratrol against human and animal viruses. Adv Virol. 2015;2015:184241. doi:10.1155/2015/184241. PMID:26693226.
67. Andrographolide. Jiang M, Sheng F, Zhang Z, et al. Andrographolide as a potent and promising antiviral agent. Chin J Nat Med. 2020;18(10):760-769.
68. Glycyrrhizin. Fiore C, Eisenhut M, Krausse R, et al. Antiviral effects of Glycyrrhiza species. Phytother Res. 2008;22(2):141-148. doi:10.1002/ptr.2295.
69. Berberine. Warowicka A, Nawrot R, Goździcka-Józefiak A. Antiviral activity of berberine. Arch Virol. 2020;165(9):1935-1945. doi:10.1007/s00705-020-04706-3.
70. Apigenin. Zakaryan H, Arabyan E, Oo A, Zandi K. Flavonoids: promising natural compounds against viral infections. Arch Virol. 2017;162(9):2539-2551. doi:10.1007/s00705-017-3417-y.
71. Luteolin. Peng M, Watanabe S, Chan KWK, et al. Luteolin restricts dengue virus replication through inhibition of the proprotein convertase furin. Antiviral Res. 2017;143:176-185. doi:10.1016/j.antiviral.2017.03.026.
72. Kaempferol. Zakaryan H, Arabyan E, Oo A, Zandi K. Flavonoids: promising natural compounds against viral infections. Arch Virol. 2017;162(9):2539-2551. doi:10.1007/s00705-017-3417-y.
73. Myricetin. Zakaryan H, Arabyan E, Oo A, Zandi K. Flavonoids: promising natural compounds against viral infections. Arch Virol. 2017;162(9):2539-2551. doi:10.1007/s00705-017-3417-y.
74. Hesperidin. Zakaryan H, Arabyan E, Oo A, Zandi K. Flavonoids: promising natural compounds against viral infections. Arch Virol. 2017;162(9):2539-2551. doi:10.1007/s00705-017-3417-y.
75. Naringenin. Tutunchi H, Naeini F, Ostadrahimi A, Hosseinzadeh-Attar MJ. Naringenin, a flavanone with antiviral and anti-inflammatory effects: a promising treatment strategy against COVID-19. Phytother Res. 2020;34(12):3137-3147. doi:10.1002/ptr.6781.
76. Genistein. Andres A, Donovan SM, Kuhlenschmidt MS. Soy isoflavones and virus infections. J Nutr Biochem. 2009;20(8):563-569. doi:10.1016/j.jnutbio.2009.04.004.
77. Silymarin/silibinin. Polyak SJ, Morishima C, Shuhart MC, Wang CC, Liu Y, Lee DYW. Inhibition of T-cell inflammatory cytokines, hepatocyte NF-κB signaling, and HCV infection by standardized silymarin. Gastroenterology. 2007;132(5):1925-1936. doi:10.1053/j.gastro.2007.02.038.
78. Epicatechin gallate. Xu J, Xu Z, Zheng W. A review of the antiviral role of green tea catechins. Molecules. 2017;22(8):1337. doi:10.3390/molecules22081337.
79. Theaflavins. Chowdhury P, Barooah AK. Tea bioactive modulate innate immunity: in perception to COVID-19 pandemic. Front Immunol. 2020;11:590716. doi:10.3389/fimmu.2020.590716.
80. Allicin. Rouf R, Uddin SJ, Sarker DK, et al. Antiviral potential of garlic (Allium sativum) and its organosulfur compounds: a systematic update of pre-clinical and clinical data. Trends Food Sci Technol. 2020;104:219-234. doi:10.1016/j.tifs.2020.08.006. Recent mechanistic review also emphasizes instability and limited clinical translation.
81. Ajoene. Rouf R, Uddin SJ, Sarker DK, et al. Antiviral potential of garlic (Allium sativum) and its organosulfur compounds: a systematic update of pre-clinical and clinical data. Trends Food Sci Technol. 2020;104:219-234. doi:10.1016/j.tifs.2020.08.006.
82. Elderberry. Hawkins J, Baker C, Cherry L, Dunne E. Black elderberry (Sambucus nigra) supplementation effectively treats upper respiratory symptoms: a meta-analysis of randomized, controlled clinical trials. Complement Ther Med. 2019;42:361-365. doi:10.1016/j.ctim.2018.12.004.
83. Echinacea. Karsch-Völk M, Barrett B, Kiefer D, Bauer R, Ardjomand-Woelkart K, Linde K. Echinacea for preventing and treating the common cold. Cochrane Database Syst Rev. 2014;(2):CD000530. doi:10.1002/14651858.CD000530.pub3.
84. Lactoferrin. Berlutti F, Pantanella F, Natalizi T, et al. Antiviral properties of lactoferrin—a natural immunity molecule. Molecules. 2011;16(8):6992-7018. doi:10.3390/molecules16086992. PMID:21847071.
85. Glycerol monolaurate/monolaurin. Thormar H, Isaacs CE, Brown HR, Barshatzky MR, Pessolano T. Inactivation of enveloped viruses and killing of cells by fatty acids and monoglycerides. Antimicrob Agents Chemother. 1987;31(1):27-31. doi:10.1128/AAC.31.1.27.
86. Lauric acid. Thormar H, Isaacs CE, Brown HR, Barshatzky MR, Pessolano T. Inactivation of enveloped viruses and killing of cells by fatty acids and monoglycerides. Antimicrob Agents Chemother. 1987;31(1):27-31. doi:10.1128/AAC.31.1.27.
87. Melatonin. Reiter RJ, Ma Q, Sharma R. Treatment of Ebola and other infectious diseases: melatonin “goes viral.” Melatonin Res. 2020;3(1):43-57. doi:10.32794/mr11250047.
88. Sulforaphane. Ordonez AA, Bullen CK, Villabona-Rueda AF, et al. Sulforaphane exhibits antiviral activity against pandemic SARS-CoV-2 and seasonal HCoV-OC43 coronaviruses in vitro and in mice. Commun Biol. 2022;5:242. doi:10.1038/s42003-022-03189-z.
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The Critical Lesson

The difference between #1 acyclovir and #65 curcumin is not simply that acyclovir is “stronger.” It is that acyclovir crossed the entire evidence FDA testing:

Biochemical antiviral effect → cell culture → mammalian pharmacology/toxicology → human dose finding → controlled human efficacy → clinically reproducible benefit.

Most experimental natural compounds remain somewhere in the first three stages. But some of these agents may still be used by 5-40 million people worldwide each year.

Yet, mammalian evidence is substantially more valuable than cell-culture evidence but still does not prove human efficacy. Tecovirimat demonstrates why this distinction matters especially well: its smallpox indication was necessarily established under the Animal Rule using rabbitpox and nonhuman-primate orthopoxvirus models plus human safety/PK data, because deliberately testing smallpox efficacy in humans is impossible. More recently, a randomized human trial in clade II mpox, published February 25, 2026, specifically examined human efficacy rather than assuming that the impressive animal findings would automatically translate to that disease.

Thus, would not describe quercetin, curcumin, resveratrol, essential oils, mushrooms, zinc, selenium, β-glucans, or sulfated polysaccharides as equivalent to licensed antiviral drugs, despite biologically interesting antiviral results. Reviews of quercetin, baicalein/baicalin, medicinal fungi and sulfated polysaccharides explicitly show the enormous gap between mechanistic/preclinical antiviral activity and established human treatment efficacy.