Herpes simplex virus (HSV) is a prevalent and persistent human pathogen belonging to the family Herpesviridae and classified as an alpha-herpesvirus. It comprises two distinct types, HSV-1 and HSV-2, which together infect a significant portion of the global population and pose substantial public health challenges. HSV-1 is typically associated with oral herpes, while HSV-2 primarily causes genital herpes; both are characterized by recurrent lesions, latent infection, and mucocutaneous discomfort. Conventional antiviral drugs such as acyclovir and its derivatives are limited by drug resistance, potential toxicity, and their inability to eradicate latent viral reservoirs. These limitations have prompted increasing interest in alternative therapeutic strategies. Phenolic acids and tannins, plant-derived polyphenolic compounds, have attracted considerable attention due to their potent antiviral properties against various viruses, including HSV. This review summarizes current research on phenolic acids and tannins as promising natural antivirals against HSV, with a focus on their mechanisms of action and efficacy in disrupting multiple stages of the HSV life cycle.

Department of Applied Ecology Faculty of Environmental Sciences Czech University of Life Sciences Prague Kamýcká 129 165 00 Prague Czech Republic

Zobrazit více v PubMed

Widener R.W., Whitley R.J. Handbook of Clinical Neurology. Volume 123. Elsevier; Amsterdam, The Netherlands: 2014. Herpes Simplex Virus; pp. 251–263. PubMed

Adler B., Sattler C., Adler H. Herpesviruses and Their Host Cells: A Successful Liaison. Trends Microbiol. 2017;25:229–241. doi: 10.1016/j.tim.2016.11.009. PubMed DOI

Petti S., Lodi G. The Controversial Natural History of Oral Herpes Simplex Virus Type 1 Infection. Oral Dis. 2019;25:1850–1865. doi: 10.1111/odi.13234. PubMed DOI

Kolokotronis A., Doumas S. Herpes Simplex Virus Infection, with Particular Reference to the Progression and Complications of Primary Herpetic Gingivostomatitis. Clin. Microbiol. Infect. 2006;12:202–211. doi: 10.1111/j.1469-0691.2005.01336.x. PubMed DOI

Gnann J.W., Whitley R.J. Herpes Simplex Encephalitis: An Update. Curr. Infect. Dis. Rep. 2017;19:13. doi: 10.1007/s11908-017-0568-7. PubMed DOI

Omarova S., Cannon A., Weiss W., Bruccoleri A., Puccio J. Genital Herpes Simplex Virus—An Updated Review. Adv. Pediatr. 2022;69:149–162. doi: 10.1016/j.yapd.2022.03.010. PubMed DOI

Harfouche M., Maalmi H., Abu-Raddad L.J. Epidemiology of Herpes Simplex Virus Type 2 in Latin America and the Caribbean: Systematic Review, Meta-Analyses and Metaregressions. Sex. Transm. Infect. 2021;97:490–500. doi: 10.1136/sextrans-2021-054972. PubMed DOI PMC

Desai D.V., Kulkarni S.S. Herpes Simplex Virus: The Interplay Between HSV, Host, and HIV-1. Viral Immunol. 2015;28:546–555. doi: 10.1089/vim.2015.0012. PubMed DOI

Corey L. Synergistic Copathogens—HIV-1 and HSV-2. N. Engl. J. Med. 2007;356:854–856. doi: 10.1056/NEJMe068302. PubMed DOI

Fatahzadeh M., Schwartz R.A. Human Herpes Simplex Virus Infections: Epidemiology, Pathogenesis, Symptomatology, Diagnosis, and Management. J. Am. Acad. Dermatol. 2007;57:737–763. doi: 10.1016/j.jaad.2007.06.027. PubMed DOI

Crimi S., Fiorillo L., Bianchi A., D’Amico C., Amoroso G., Gorassini F., Mastroieni R., Marino S., Scoglio C., Catalano F., et al. Herpes Virus, Oral Clinical Signs and QoL: Systematic Review of Recent Data. Viruses. 2019;11:463. doi: 10.3390/v11050463. PubMed DOI PMC

Pinninti S.G., Kimberlin D.W. Neonatal Herpes Simplex Virus Infections. Semin. Perinatol. 2018;42:168–175. doi: 10.1053/j.semperi.2018.02.004. PubMed DOI

Hammad W.A.B., Konje J.C. Herpes Simplex Virus Infection in Pregnancy—An Update. Eur. J. Obstet. Gynecol. Reprod. Biol. 2021;259:38–45. doi: 10.1016/j.ejogrb.2021.01.055. PubMed DOI

Mindel A. Psychological and Psychosexual Implications of Herpes Simplex Virus Infections. Scand. J. Infect. Dis. Suppl. 1996;100:27–32. PubMed

Mindel A., Marks C. Psychological Symptoms Associated with Genital Herpes Virus Infections: Epidemiology and Approaches to Management. CNS Drugs. 2005;19:303–312. doi: 10.2165/00023210-200519040-00003. PubMed DOI

Schalkwijk H.H., Snoeck R., Andrei G. Acyclovir Resistance in Herpes Simplex Viruses: Prevalence and Therapeutic Alternatives. Biochem. Pharmacol. 2022;206:115322. doi: 10.1016/j.bcp.2022.115322. PubMed DOI

Hassan S.T.S., Šudomová M., Berchová-Bímová K., Šmejkal K., Echeverría J. Psoromic Acid, a Lichen-Derived Molecule, Inhibits the Replication of HSV-1 and HSV-2, and Inactivates HSV-1 DNA Polymerase: Shedding Light on Antiherpetic Properties. Molecules. 2019;24:2912. doi: 10.3390/molecules24162912. PubMed DOI PMC

Lv W., Zhou L., Wu J., Cheng J., Duan Y., Qian W. Anti-HSV-1 Agents: An Update. Front. Pharmacol. 2025;15:1451083. doi: 10.3389/fphar.2024.1451083. PubMed DOI PMC

Treml J., Gazdová M., Šmejkal K., Šudomová M., Kubatka P., Hassan S.T.S. Natural Products-Derived Chemicals: Breaking Barriers to Novel Anti-HSV Drug Development. Viruses. 2020;12:154. doi: 10.3390/v12020154. PubMed DOI PMC

Zhu S., Viejo-Borbolla A. Pathogenesis and Virulence of Herpes Simplex Virus. Virulence. 2021;12:2670–2702. doi: 10.1080/21505594.2021.1982373. PubMed DOI PMC

Denes C.E., Everett R.D., Diefenbach R.J. Tour de Herpes: Cycling Through the Life and Biology of HSV-1. In: Diefenbach R.J., Fraefel C., editors. Herpes Simplex Virus. Volume 2060. Methods in Molecular Biology; Springer New York; New York, NY, USA: 2020. pp. 1–30. PubMed

Šudomová M., Hassan S.T.S. Flavonoids with Anti-Herpes Simplex Virus Properties: Deciphering Their Mechanisms in Disrupting the Viral Life Cycle. Viruses. 2023;15:2340. doi: 10.3390/v15122340. PubMed DOI PMC

Patel A., Patel R. Recent Insights into HSV Infection and Disease: Results of Wider Genome Analysis. Curr. Opin. Infect. Dis. 2019;32:51–55. doi: 10.1097/QCO.0000000000000512. PubMed DOI

Furlong D., Swift H., Roizman B. Arrangement of Herpesvirus Deoxyribonucleic Acid in the Core. J. Virol. 1972;10:1071–1074. doi: 10.1128/jvi.10.5.1071-1074.1972. PubMed DOI PMC

Kuny C.V., Szpara M.L. Alphaherpesvirus Genomics: Past, Present and Future. Curr. Issues Mol. Biol. 2022;42:41–80. doi: 10.21775/cimb.042.041. PubMed DOI PMC

Bhowmik D., Zhu F. Evasion of Intracellular DNA Sensing by Human Herpesviruses. Front. Cell. Infect. Microbiol. 2021;11:647992. doi: 10.3389/fcimb.2021.647992. PubMed DOI PMC

Homa F.L., Brown J.C. Capsid Assembly and DNA Packaging in Herpes Simplex Virus. Rev. Med. Virol. 1997;7:107–122. doi: 10.1002/(SICI)1099-1654(199707)7:2<107::AID-RMV191>3.0.CO;2-M. PubMed DOI

Goshima F., Watanabe D., Takakuwa H., Wada K., Daikoku T., Yamada M., Nishiyama Y. Herpes Simplex Virus UL17 Protein Is Associated with B Capsids and Colocalizes with ICP35 and VP5 in Infected Cells. Arch. Virol. 2000;145:417–426. doi: 10.1007/s007050050033. PubMed DOI

Ding X., Neumann D.M., Zhu L. Host Factors Associated with Either VP16 or VP16-induced Complex Differentially Affect HSV-1 Lytic Infection. Rev. Med. Virol. 2022;32:e2394. doi: 10.1002/rmv.2394. PubMed DOI PMC

Shiflett L.A., Read G.S. mRNA Decay during Herpes Simplex Virus (HSV) Infections: Mutations That Affect Translation of an mRNA Influence the Sites at Which It Is Cleaved by the HSV Virion Host Shutoff (Vhs) Protein. J. Virol. 2013;87:94–109. doi: 10.1128/JVI.01557-12. PubMed DOI PMC

DuRaine G., Wisner T.W., Johnson D.C. Characterization of the Herpes Simplex Virus (HSV) Tegument Proteins That Bind to gE/gI and US9, Which Promote Assembly of HSV and Transport into Neuronal Axons. J. Virol. 2020;94:e01113-20. doi: 10.1128/JVI.01113-20. PubMed DOI PMC

Owen D., Crump C., Graham S. Tegument Assembly and Secondary Envelopment of Alphaherpesviruses. Viruses. 2015;7:5084–5114. doi: 10.3390/v7092861. PubMed DOI PMC

Frost T.C., Salnikov M., Rice S.A. Enhancement of HSV-1 Cell-Free Virion Release by the Envelope Protein gC. Virology. 2024;596:110120. doi: 10.1016/j.virol.2024.110120. PubMed DOI PMC

Vallbracht M., Backovic M., Klupp B.G., Rey F.A., Mettenleiter T.C. Advances in Virus Research. Volume 104. Elsevier; Amsterdam, The Netherlands: 2019. Common Characteristics and Unique Features: A Comparison of the Fusion Machinery of the Alphaherpesviruses Pseudorabies Virus and Herpes Simplex Virus; pp. 225–281. PubMed

Kukhanova M.K., Korovina A.N., Kochetkov S.N. Human Herpes Simplex Virus: Life Cycle and Development of Inhibitors. Biochem. Mosc. 2014;79:1635–1652. doi: 10.1134/S0006297914130124. PubMed DOI

Singh N., Zachariah S., Phillips A.T., Tscharke D. Lytic Promoter Activity during Herpes Simplex Virus Latency Is Dependent on Genome Location. J. Virol. 2024;98:e01258-24. doi: 10.1128/jvi.01258-24. PubMed DOI PMC

Azab W., Osterrieder K. Initial Contact: The First Steps in Herpesvirus Entry. In: Osterrieder K., editor. Cell Biology of Herpes Viruses. Volume 223. Springer International Publishing; Cham, Switzerland: 2017. pp. 1–27. Advances in Anatomy, Embryology and Cell Biology. PubMed

Connolly S.A., Jardetzky T.S., Longnecker R. The Structural Basis of Herpesvirus Entry. Nat. Rev. Microbiol. 2021;19:110–121. doi: 10.1038/s41579-020-00448-w. PubMed DOI PMC

Arii J., Kawaguchi Y. The Role of HSV Glycoproteins in Mediating Cell Entry. In: Kawaguchi Y., Mori Y., Kimura H., editors. Human Herpesviruses. Volume 1045. Springer; Singapore: 2018. pp. 3–21. Advances in Experimental Medicine and Biology. PubMed

Pertel P.E., Fridberg A., Parish M.L., Spear P.G. Cell Fusion Induced by Herpes Simplex Virus Glycoproteins gB, gD, and gH-gL Requires a gD Receptor but Not Necessarily Heparan Sulfate. Virology. 2001;279:313–324. doi: 10.1006/viro.2000.0713. PubMed DOI

Heming J.D., Conway J.F., Homa F.L. Herpesvirus Capsid Assembly and DNA Packaging. In: Osterrieder K., editor. Cell Biology of Herpes Viruses. Volume 223. Springer International Publishing; Cham, Switzerland: 2017. pp. 119–142. Advances in Anatomy, Embryology and Cell Biology. PubMed PMC

Adlakha M., Livingston C.M., Bezsonova I., Weller S.K. The Herpes Simplex Virus 1 Immediate Early Protein ICP22 Is a Functional Mimic of a Cellular J Protein. J. Virol. 2020;94:e01564-19. doi: 10.1128/JVI.01564-19. PubMed DOI PMC

Baines J.D. Herpes Simplex Virus Capsid Assembly and DNA Packaging: A Present and Future Antiviral Drug Target. Trends Microbiol. 2011;19:606–613. doi: 10.1016/j.tim.2011.09.001. PubMed DOI

Zarrouk K., Piret J., Boivin G. Herpesvirus DNA Polymerases: Structures, Functions and Inhibitors. Virus Res. 2017;234:177–192. doi: 10.1016/j.virusres.2017.01.019. PubMed DOI

Skaliter R., Lehman I.R. Rolling Circle DNA Replication in Vitro by a Complex of Herpes Simplex Virus Type 1-Encoded Enzymes. Proc. Natl. Acad. Sci. USA. 1994;91:10665–10669. doi: 10.1073/pnas.91.22.10665. PubMed DOI PMC

Weller S.K., Coen D.M. Herpes Simplex Viruses: Mechanisms of DNA Replication. Cold Spring Harb. Perspect. Biol. 2012;4:a013011. doi: 10.1101/cshperspect.a013011. PubMed DOI PMC

Cohrs R.J., Badani H., Bos N., Scianna C., Hoskins I., Baird N.L., Gilden D. Alphaherpesvirus DNA Replication in Dissociated Human Trigeminal Ganglia. J. Neurovirol. 2016;22:688–694. doi: 10.1007/s13365-016-0450-7. PubMed DOI PMC

Muylaert I., Tang K.-W., Elias P. Replication and Recombination of Herpes Simplex Virus DNA. J. Biol. Chem. 2011;286:15619–15624. doi: 10.1074/jbc.R111.233981. PubMed DOI PMC

Taylor K.E., Mossman K.L. Cellular Protein WDR11 Interacts with Specific Herpes Simplex Virus Proteins at the Trans-Golgi Network To Promote Virus Replication. J. Virol. 2015;89:9841–9852. doi: 10.1128/JVI.01705-15. PubMed DOI PMC

Cohen J.I. Herpesvirus Latency. J. Clin. Investig. 2020;130:3361–3369. doi: 10.1172/JCI136225. PubMed DOI PMC

Lomonte P. Herpesvirus Latency: On the Importance of Positioning Oneself. In: Osterrieder K., editor. Cell Biology of Herpes Viruses. Volume 223. Springer International Publishing; Cham, Switzerland: 2017. pp. 95–117. Advances in Anatomy, Embryology and Cell Biology. PubMed

Wechsler S.L., Nesburn A.B., Watson R., Slanina S.M., Ghiasi H. Fine Mapping of the Latency-Related Gene of Herpes Simplex Virus Type 1: Alternative Splicing Produces Distinct Latency-Related RNAs Containing Open Reading Frames. J. Virol. 1988;62:4051–4058. doi: 10.1128/jvi.62.11.4051-4058.1988. PubMed DOI PMC

Efstathiou S., Preston C.M. Towards an Understanding of the Molecular Basis of Herpes Simplex Virus Latency. Virus Res. 2005;111:108–119. doi: 10.1016/j.virusres.2005.04.017. PubMed DOI

Bloom D.C. HSV LAT and neuronal survival. Int. Rev. Immunol. 2004;23:187–198. doi: 10.1080/08830180490265592. PubMed DOI

Harrison K.S., Jones C. Regulation of Herpes Simplex Virus Type 1 Latency-Reactivation Cycle and Ocular Disease by Cellular Signaling Pathways. Exp. Eye Res. 2022;218:109017. doi: 10.1016/j.exer.2022.109017. PubMed DOI PMC

Roizman B., Whitley R.J. An Inquiry into the Molecular Basis of HSV Latency and Reactivation. Annu. Rev. Microbiol. 2013;67:355–374. doi: 10.1146/annurev-micro-092412-155654. PubMed DOI

Ho D.Y., Enriquez K., Multani A. Herpesvirus Infections Potentiated by Biologics. Infect. Dis. Clin. N. Am. 2020;34:311–339. doi: 10.1016/j.idc.2020.02.006. PubMed DOI

Turuvekere Vittala Murthy N., Agrahari V., Chauhan H. Polyphenols against Infectious Diseases: Controlled Release Nano-Formulations. Eur. J. Pharm. Biopharm. 2021;161:66–79. doi: 10.1016/j.ejpb.2021.02.003. PubMed DOI

Kumar N., Goel N. Phenolic Acids: Natural Versatile Molecules with Promising Therapeutic Applications. Biotechnol. Rep. 2019;24:e00370. doi: 10.1016/j.btre.2019.e00370. PubMed DOI PMC

Durazzo A., Lucarini M., Souto E.B., Cicala C., Caiazzo E., Izzo A.A., Novellino E., Santini A. Polyphenols: A Concise Overview on the Chemistry, Occurrence, and Human Health. Phytother. Res. 2019;33:2221–2243. doi: 10.1002/ptr.6419. PubMed DOI

Di Lorenzo C., Colombo F., Biella S., Stockley C., Restani P. Polyphenols and Human Health: The Role of Bioavailability. Nutrients. 2021;13:273. doi: 10.3390/nu13010273. PubMed DOI PMC

Cory H., Passarelli S., Szeto J., Tamez M., Mattei J. The Role of Polyphenols in Human Health and Food Systems: A Mini-Review. Front. Nutr. 2018;5:87. doi: 10.3389/fnut.2018.00087. PubMed DOI PMC

Hassan S.T.S., Šudomová M., Mazurakova A., Kubatka P. Insights into Antiviral Properties and Molecular Mechanisms of Non-Flavonoid Polyphenols against Human Herpesviruses. Int. J. Mol. Sci. 2022;23:13891. doi: 10.3390/ijms232213891. PubMed DOI PMC

Hassan S.T.S., Masarčíková R., Berchová K. Bioactive Natural Products with Anti-Herpes Simplex Virus Properties. J. Pharm. Pharmacol. 2015;67:1325–1336. doi: 10.1111/jphp.12436. PubMed DOI

Molino S., Pilar Francino M., Ángel Rufián Henares J. Why Is It Important to Understand the Nature and Chemistry of Tannins to Exploit Their Potential as Nutraceuticals? Food Res. Int. 2023;173:113329. doi: 10.1016/j.foodres.2023.113329. PubMed DOI

Zhang L., Han Z., Granato D. Advances in Food and Nutrition Research. Volume 98. Elsevier; Amsterdam, The Netherlands: 2021. Polyphenols in Foods: Classification, Methods of Identification, and Nutritional Aspects in Human Health; pp. 1–33. PubMed

Seidi F., Liu Y., Huang Y., Xiao H., Crespy D. Chemistry of Lignin and Condensed Tannins as Aromatic Biopolymers. Chem. Soc. Rev. 2025;54:3140–3232. doi: 10.1039/D4CS00440J. PubMed DOI

Rousserie P., Rabot A., Geny-Denis L. From Flavanols Biosynthesis to Wine Tannins: What Place for Grape Seeds? J. Agric. Food Chem. 2019;67:1325–1343. doi: 10.1021/acs.jafc.8b05768. PubMed DOI

Chojnacka K., Skrzypczak D., Izydorczyk G., Mikula K., Szopa D., Witek-Krowiak A. Antiviral Properties of Polyphenols from Plants. Foods. 2021;10:2277. doi: 10.3390/foods10102277. PubMed DOI PMC

Luca S.V., Macovei I., Bujor A., Miron A., Skalicka-Woźniak K., Aprotosoaie A.C., Trifan A. Bioactivity of Dietary Polyphenols: The Role of Metabolites. Crit. Rev. Food Sci. Nutr. 2020;60:626–659. doi: 10.1080/10408398.2018.1546669. PubMed DOI

Lin L.-T., Chen T.-Y., Chung C.-Y., Noyce R.S., Grindley T.B., McCormick C., Lin T.-C., Wang G.-H., Lin C.-C., Richardson C.D. Hydrolyzable Tannins (Chebulagic Acid and Punicalagin) Target Viral Glycoprotein-Glycosaminoglycan Interactions To Inhibit Herpes Simplex Virus 1 Entry and Cell-to-Cell Spread. J. Virol. 2011;85:4386–4398. doi: 10.1128/JVI.01492-10. PubMed DOI PMC

Zhang H., Cheng L., Ju F. In Vitro and Silico Studies of Geraniin Interfering with HSV-2 Replication by Targeting Glycoprotein D. Nat. Prod. Res. 2024;38:2053–2059. doi: 10.1080/14786419.2023.2241153. PubMed DOI

Rudrapal M., Mishra A.K., Rani L., Sarwa K.K., Zothantluanga J.H., Khan J., Kamal M., Palai S., Bendale A.R., Talele S.G., et al. Nanodelivery of Dietary Polyphenols for Therapeutic Applications. Molecules. 2022;27:8706. doi: 10.3390/molecules27248706. PubMed DOI PMC

Aatif M. Current Understanding of Polyphenols to Enhance Bioavailability for Better Therapies. Biomedicines. 2023;11:2078. doi: 10.3390/biomedicines11072078. PubMed DOI PMC

Scalbert A., Manach C., Morand C., Rémésy C., Jiménez L. Dietary Polyphenols and the Prevention of Diseases. Crit. Rev. Food Sci. Nutr. 2005;45:287–306. doi: 10.1080/1040869059096. PubMed DOI

Yahfoufi N., Alsadi N., Jambi M., Matar C. The Immunomodulatory and Anti-Inflammatory Role of Polyphenols. Nutrients. 2018;10:1618. doi: 10.3390/nu10111618. PubMed DOI PMC

Shahidi F., Ambigaipalan P. Phenolics and Polyphenolics in Foods, Beverages and Spices: Antioxidant Activity and Health Effects—A Review. J. Funct. Foods. 2015;18:820–897. doi: 10.1016/j.jff.2015.06.018. DOI

Montenegro-Landívar M.F., Tapia-Quirós P., Vecino X., Reig M., Valderrama C., Granados M., Cortina J.L., Saurina J. Polyphenols and Their Potential Role to Fight Viral Diseases: An Overview. Sci. Total Environ. 2021;801:149719. doi: 10.1016/j.scitotenv.2021.149719. PubMed DOI PMC

Hassan S.T.S., Švajdlenka E., Berchová-Bímová K. Hibiscus Sabdariffa L. and Its Bioactive Constituents Exhibit Antiviral Activity against HSV-2 and Anti-Enzymatic Properties against Urease by an ESI-MS Based Assay. Molecules. 2017;22:722. doi: 10.3390/molecules22050722. PubMed DOI PMC

Borenstein R., Hanson B.A., Markosyan R.M., Gallo E.S., Narasipura S.D., Bhutta M., Shechter O., Lurain N.S., Cohen F.S., Al-Harthi L., et al. Ginkgolic Acid Inhibits Fusion of Enveloped Viruses. Sci. Rep. 2020;10:4746. doi: 10.1038/s41598-020-61700-0. PubMed DOI PMC

Sochocka M., Sobczyński M., Ochnik M., Zwolińska K., Leszek J. Hampering Herpesviruses HHV-1 and HHV-2 Infection by Extract of Ginkgo Biloba (EGb) and Its Phytochemical Constituents. Front. Microbiol. 2019;10:2367. doi: 10.3389/fmicb.2019.02367. PubMed DOI PMC

Bhutta M.S., Shechter O., Gallo E.S., Martin S.D., Jones E., Doncel G.F., Borenstein R. Ginkgolic Acid Inhibits Herpes Simplex Virus Type 1 Skin Infection and Prevents Zosteriform Spread in Mice. Viruses. 2021;13:86. doi: 10.3390/v13010086. PubMed DOI PMC

Di Sotto A., Di Giacomo S., Amatore D., Locatelli M., Vitalone A., Toniolo C., Rotino G.L., Lo Scalzo R., Palamara A.T., Marcocci M.E., et al. A Polyphenol Rich Extract from Solanum Melongena L. DR2 Peel Exhibits Antioxidant Properties and Anti-Herpes Simplex Virus Type 1 Activity In Vitro. Molecules. 2018;23:2066. doi: 10.3390/molecules23082066. PubMed DOI PMC

Langland J., Jacobs B., Wagner C.E., Ruiz G., Cahill T.M. Antiviral Activity of Metal Chelates of Caffeic Acid and Similar Compounds towards Herpes Simplex, VSV-Ebola Pseudotyped and Vaccinia Viruses. Antivir. Res. 2018;160:143–150. doi: 10.1016/j.antiviral.2018.10.021. PubMed DOI

AbouAitah K., Allayh A.K., Wojnarowicz J., Shaker Y.M., Swiderska-Sroda A., Lojkowski W. Nanoformulation Composed of Ellagic Acid and Functionalized Zinc Oxide Nanoparticles Inactivates DNA and RNA Viruses. Pharmaceutics. 2021;13:2174. doi: 10.3390/pharmaceutics13122174. PubMed DOI PMC

Todorova N., Rangelov M., Dincheva I., Badjakov I., Enchev V., Markova N. Potential of Hydroxybenzoic Acids from Graptopetalum Paraguayense for Inhibiting of Herpes Simplex Virus DNA Polymerase—Metabolome Profiling, Molecular Docking and Quantum-Chemical Analysis. Pharmacia. 2022;69:113–123. doi: 10.3897/pharmacia.69.e79467. DOI

EL-Aguel A., Pennisi R., Smeriglio A., Kallel I., Tamburello M.P., D’Arrigo M., Barreca D., Gargouri A., Trombetta D., Mandalari G., et al. Punica granatum Peel and Leaf Extracts as Promising Strategies for HSV-1 Treatment. Viruses. 2022;14:2639. doi: 10.3390/v14122639. PubMed DOI PMC

Aljohani A.K., Maghrabi N.A., Alrehili O.M., Alharbi A.S., Alsihli R.S., Alharthe A.M., Albladi R.S., Alosaimi K.A., Albadrani B.M., Miski S.F., et al. Ajwa Date Extract (Phoenix Dactylifera L.): Phytochemical Analysis, Antiviral Activity against Herpes Simplex Virus-I and Coxsackie B4 Virus, and in Silico Study. Saudi Med. J. 2025;46:26–35. doi: 10.15537/smj.2025.46.1.20240780. PubMed DOI PMC

Siqueira E.M.d.S., Lima T.L.C., Boff L., Lima S.G.M., Lourenço E.M.G., Ferreira É.G., Barbosa E.G., Machado P.R.L., Farias K.J.S., Ferreira L.d.S., et al. Antiviral Potential of Spondias Mombin L. Leaves Extract Against Herpes Simplex Virus Type-1 Replication Using In Vitro and In Silico Approaches. Planta Med. 2020;86:505–515. doi: 10.1055/a-1135-9066. PubMed DOI

Kesharwani A., Polachira S.K., Nair R., Agarwal A., Mishra N.N., Gupta S.K. Anti-HSV-2 Activity of Terminalia Chebula Retz Extract and Its Constituents, Chebulagic and Chebulinic Acids. BMC Complement. Altern. Med. 2017;17:110. doi: 10.1186/s12906-017-1620-8. PubMed DOI PMC

Vilhelmova-Ilieva N., Jacquet R., Deffieux D., Pouységu L., Sylla T., Chassaing S., Nikolova I., Quideau S., Galabov A.S. Anti-Herpes Simplex Virus Type 1 Activity of Specially Selected Groups of Tannins. Drug Res. 2019;69:373–374. doi: 10.1055/a-0640-2557. PubMed DOI

Vilhelmova-Ilieva N., Jacquet R., Quideau S., Galabov A.S. Ellagitannins as Synergists of ACV on the Replication of ACV-Resistant Strains of HSV 1 and 2. Antivir. Res. 2014;110:104–114. doi: 10.1016/j.antiviral.2014.07.017. PubMed DOI

Stoyanova A., Popatanasov A., Rashev V., Tancheva L., Quideau S., Galabov A.S. Effect of Castalagin against HSV-1 Infection in Newborn Mice. Nat. Prod. Res. 2023;37:4156–4161. doi: 10.1080/14786419.2023.2173191. PubMed DOI

Guo Y.-J., Luo T., Wu F., Liu H., Li H.-R., Mei Y.-W., Zhang S.-L., Tao J.-Y., Dong J.-H., Fang Y., et al. Corilagin Protects Against HSV1 Encephalitis Through Inhibiting the TLR2 Signaling Pathways In Vivo and In Vitro. Mol. Neurobiol. 2015;52:1547–1560. doi: 10.1007/s12035-014-8947-7. PubMed DOI

Jin F., Ma K., Chen M., Zou M., Wu Y., Li F., Wang Y. Pentagalloylglucose Blocks the Nuclear Transport and the Process of Nucleocapsid Egress to Inhibit HSV-1 Infection. Jpn. J. Infect. Dis. 2016;69:135–142. doi: 10.7883/yoken.JJID.2015.137. PubMed DOI

Arunkumar J., Rajarajan S. Study on Antiviral Activities, Drug-Likeness and Molecular Docking of Bioactive Compounds of Punica granatum L. to Herpes Simplex Virus-2 (HSV-2) Microb. Pathog. 2018;118:301–309. doi: 10.1016/j.micpath.2018.03.052. PubMed DOI

Houston D.M.J., Bugert J.J., Denyer S.P., Heard C.M. Potentiated Virucidal Activity of Pomegranate Rind Extract (PRE) and Punicalagin against Herpes Simplex Virus (HSV) When Co-Administered with Zinc (II) Ions, and Antiviral Activity of PRE against HSV and Aciclovir-Resistant HSV. PLoS ONE. 2017;12:e0179291. doi: 10.1371/journal.pone.0179291. PubMed DOI PMC

Szymańska E., Orłowski P., Winnicka K., Tomaszewska E., Bąska P., Celichowski G., Grobelny J., Basa A., Krzyżowska M. Multifunctional Tannic Acid/Silver Nanoparticle-Based Mucoadhesive Hydrogel for Improved Local Treatment of HSV Infection: In Vitro and In Vivo Studies. Int. J. Mol. Sci. 2018;19:387. doi: 10.3390/ijms19020387. PubMed DOI PMC

Orłowski P., Kowalczyk A., Tomaszewska E., Ranoszek-Soliwoda K., Węgrzyn A., Grzesiak J., Celichowski G., Grobelny J., Eriksson K., Krzyzowska M. Antiviral Activity of Tannic Acid Modified Silver Nanoparticles: Potential to Activate Immune Response in Herpes Genitalis. Viruses. 2018;10:524. doi: 10.3390/v10100524. PubMed DOI PMC

Fahim M.S., Brawner T.A., Hall D.G. New Treatment for Herpes Simplex Virus Type 2 [Ultrasound and Zinc, Urea and Tannic Acid Ointment]. Part II: Female Patients. J. Med. 1980;11:143–167. PubMed