Background: Extracts and essential oils of medicinal plants are increasingly of interest as novel drugs for antiherpetic agents, since the herpes simplex virus (HSV) might develop resistance to commonly used antiviral drugs. Methods: An aqueous extract of Melissa officinalis as well as phenolic extract compounds, i.e. caffeic acid, p-coumaric acid and rosmarinic acid were examined for their antiviral activity against herpes simplex virus type 1 (HSV-1) in vitro. Results: When drugs were added to HSV-1-infected cells, no antiviral effect was observed as determined by plaque reduction assay and analysis of expression of viral protein ICP0. However, the Melissa extract demonstrated a high virucidal activity against HSV-1, even at very low concentrations of 1.5 µg/ml, whereas similar results for phenolic compounds were only achieved at 100 times higher concentrations. Besides the virucidal activity, the Melissa extract and rosmarinic acid inhibited HSV-1 attachment to host cells in a dose-dependent manner. These results indicate that rosmarinic acid was the main contributor to the antiviral activity of Melissa extract. However, the selectivity index of Melissa extract of 875 against HSV is superior to the selectivity indices of single constituents. Conclusion: Melissa extract exhibits low toxicity, is virucidal and affects HSV-1 attachment to host cells in vitro.

Whitley RJ, Roizman B: Herpes simplex virus infections. Lancet 2001;357:1513–1518.
Whitley RJ, Levin M, Barton N, Hershey BJ, Davis G, Keeney RE, Welchel J, Diethelm AG, Kartus P, Soong SJ: Infections caused by herpes simplex in the immunocompromised host: natural history and topical acyclovir therapy. J Infect Dis 1984;150:323–329.
Brady RC, Bernstein DI: Treatment of herpes simplex virus infections. Antiviral Res 2004;61:73–81.
De Clercq E: Antiviral drugs in current clinical use. J Clin Virol 2004;30:115–133.
Efferth T: Natural products pave their way in cancer therapy. Cancer Biol Ther 2009;8:1869–1870.
Wölbling RH, Leonhardt K: Local therapy of herpes simplex with dried extract from Melissa officinalis. Phytomedicine 1994;1:25–31.
Saller R, Buechi S, Meyrat R, Schmidhauser C: Combined herbal preparation for topical treatment of herpes labialis. Forsch Komplementmed 2001;8:373–382.
Bozin B, Mimica-Dukic N, Samojlik I, Jovin E: Antimicrobial and antioxidant properties of rosemary and sage (Rosmarinus officinalis L. and Salvia officinalis L., Lamiaceae) essential oils. J Agric Food Chem 2007;55:7879–7885.
Moreno S, Scheyer T, Romano CS, Vojnov AA: Antioxidant and antimicrobial activities of rosemary extracts linked to their polyphenol composition. Free Radic Res 2006;40:223–231.
Fu Y, Zu Y, Chen L, Efferth T, Liang H, Liu Z, Liu W: Investigation of antibacterial activity of rosemary essential oil against Propionibacterium acnes with atomic force microscopy. Planta Med 2007;73:1275–1280.
Vanden Berghe DA, Vlietinck AJ, Van Hoof L: Plant products as potential antiviral agents. Bull Inst Pasteur 1986;84:101–147.
Koytchev R, Alken RG, Dundarov S: Balm mint extract (Lo-701) for topical treatment of recurring herpes labialis. Phytomedicine 1999;6:225–230.
Gaby AR: Natural remedies for herpes simplex. Altern Med Rev 2006;11:93–101.
Debiaggi M, Tateo F, Cereda PM, Pagani L, Landini P, Romero E: Effect of a Rosmarinus officinalis L. fraction on uninfected and herpes simplex virus infected cells. Ann Microbiol Enzimol 1989;39:181–194.
Carnat P, Carnat A, Fraisse D, Lamaison J: The aromatic and polyphenolic composition of lemon balm (Melissa officinalis L. subsp. officinalis) tea. Pharma Acta Helv 1998;72:301–305.
Nolkemper S, Reichling J, Stintzing FC, Carle R, Schnitzler P: Antiviral effect of aqueous extracts from species of the Lamiaceae family against herpes simplex virus type 1 and type 2 in vitro. Planta Med 2006;72:1378–1382.
Geuenich S, Goffinet C, Venzke S, Nolkemper S, Baumann I, Plinkert P, Reichling J, Keppler OT: Aqueous extracts from peppermint, sage and lemon balm leaves display potent anti-HIV-1 activity by increasing the virion density. Retrovirology 2008;5:27.
Oruga J, Vlase L, Toiu A, Benedec D, Duda M: Evaluation of phenolic acid derivatives and essential oil content in some Melissa officinalis L. varieties. Farmacia 2008;58:764–769.
Fecka I, Turek S: Determination of water-soluble polyphenolic compounds in commercial herbal teas from Lamiaceae: peppermint, Melissa, and sage. J Agric Food Chem 2007;55:10908–10917.
Agata I, Kusakabe H, Hatano T, Nishibe S, Okuda T: Melitric acids A and B, new trimeric caffeic acid derivatives from Melissa officinalis. Chem Pharm Bull 1993;41:1608–1611.
Patora J, Klinek B: Flavonoids from lemon balm (Melissa officinalis L., Lamiaceae). Acta Pol Pharm 2002;59:39–143.
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;51:1859–1862.
Söderberg T, Johannson A, Gref R: Toxic effects of some conifer resin acids and tea tree oil on human epithelial and fibroblast cells. Toxicology 1996;107:99–109.
Cheng HY, Lin CC, Lin TC: Antiherpes simplex virus type 2 activity of casuarinin from the bark of Terminalia arjuna Linn. Antiviral Res 2002;55:447–455.
Su CT, Hsu JT, Hsieh HP, Lin PH, Chen TC, Kao CL, Lee CN, Chang SY: Anti-HSV activity of digitoxin and its possible mechanisms. Antiviral Res 2008;79:62–70.
Cheng HY, Lin TC, Yang CM, Wang KC, Lin LT, Lin CC: Putranjivain A from Euphorbia jolkini inhibits both virus entry and late stage replication of herpes simplex virus type 2 in vitro. J Antimicrob Chemother 2004;53:577–583.
Khan MT, Ather A, Thompson K, Gambari R: Extracts and molecules from medicinal plants against herpes simplex viruses. Antiviral Res 2005;67:107–119.
Akhtar J, Shukla D: Viral entry mechanisms: cellular and viral mediators of herpes simplex virus entry. FEBS J 2009;276:7228–7236.
Halle W, Göres E: Prediction of LD50 values by cell culture. Pharmazie 1987;42:245–248.
Mazzanti G, Battinelli L, Pompeo C, Serrilli AM, Rossi R, Sauzullo I, Mengoni F, Vullo V: Inhibitory activity of Melissa officinalis L. extract on herpes simplex virus type 2 replication. Nat Prod Res 2008;22:1433–1440.
Chiang LC, Chiang W, Chang MY, Ng LT, Lin CC: Antiviral activity of Plantago major extracts and related compounds in vitro. Antiviral Res 2002;55:53–62.
Schneider S, Reichling J, Stintzing FC, Messerschmidt S, Meyer U, Schnitzler P: Anti-herpetic properties of hydroalcoholic extracts and pressed juice from Echinacea pallida. Planta Med 2010;76:265–272.
Gescher K, Hensel A, Hafezi W, Derksen A, Kühn J: Oligomeric proanthocyanidins from Rumex acetosa L. inhibit the attachment of herpes simplex virus type-1. Antiviral Res 2011;89:9–18.
Gescher K, Kühn J, Hafezi W, Louis A, Derksen A, Deters A, Lorentzen E, Hensel A: Inhibition of viral adsorption and penetration by an aqueous extract from Rhododendron ferrugineum L. as antiviral principle against herpes simplex virus type-1. Fitoterapia 2011;82:408–413.
Bandyopadhyay SS, Heidary Navid M, Ghosh T, Schnitzler P, Ray B: Structural features and in vitro antiviral activities of sulfated polysaccharides from Sphacelaria indica. Phytochemistry 2011;72:276–283.
Romanutti C, Bruttomesso AC, Castilla V, Galagovsky LR, Wachsman MB: Anti-adenovirus activity of epiandrosterone and dehydroepiandrosterone derivatives. Chemotherapy 2010;56:158–165.
Esimone CO, Grunwald T, Nworu CS, Kuate S, Proksch P, Überla K: Broad spectrum antiviral fractions from the lichen Ramalina farinacea (L.) Ach. Chemotherapy 2009;55:119–126.
Efferth T, Koch E: Complex interactions between phytochemicals. The multi-target therapeutic concept of phytotherapy. Curr Drug Targets 2011;12:122–132.
Astani A, Reichling J, Schnitzler P: Screening for antiviral activities of isolated compounds from essential oils. Evid Based Complement Alternat Med DOI: 10.1093/ecam/nep187.
Cos P, Vlietinck AJ, Berghe DV, Maes L: Anti-infective potential of natural products: how to develop a stronger in vitro ‘proof-of-concept’. J Ethnopharmacol 2006;106:290–302.
Bergefall K, Trybala E, Johansson M, Uyama T, Naito S, Yamada S, Kitagawa H, Sugahara K, Bergstrom T: Chondroitin sulfate characterized by the E-disaccharide unit is a potent inhibitor of herpes simplex virus infectivity and provides the virus binding sites on gro2C cells. J Biol Chem 2005;280:32193–32199.
Garozzo A, Timpanaro R, Bisignano B, Furneri PM, Bisignano G, Castro A: In vitro antiviral activity of Melaleuca alternifolia essential oil. Lett Appl Microbiol 2009;49:806–808.
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