Thymidine kinase enzyme of HSV-1 was selected to identify putative functional sites and alternative drug molecules through molecular docking .The functional sites were predicted by PINTS, Q-Site finder and PROFUNC servers. A total of 62 antiviral plant metabolites and 13 drug molecules were docked against both the chains of Thymidine kinase enzyme using Patchdock tool. The plant metabolite Geraniin has produced higher score (5680 (chain A), 6562(chain B)) than the commercially known anti-herpes compound Acyclovir (3504 (chain A), 3264 (chain B)). In addition, Gemdockv2.0 also produced the lower best fitness values for Geraniin (-130.123226 (chain A), -132.309075 (chain B)) as compared to Acyclovir (-102.182402 (chain A), -84.599474 (chain B)). Furthermore, docking through Autodock4 by considering the predicted site as a grid centre also produced lowest docking energy of -13.40 Kcal/mol (chain A), -15.17Kcal/mol (chain B) for Geraniin compound in comparison to Acyclovir -7.48Kcal/mol (chain A), -7.96Kcal/mol (chain B). Geraniin firmly binds at the cavity of the enzyme 3F0T (A and B chains) at these surrounding residues: H58 G59 M60 G61 K62 T63 T64 T66 Q67 L69 V70 A71 G73 E83 W88 R89 M85 E95 I97 Y101 K219 D162 R220 R222 P223 E225. Moreover, this compound makes appropriate hydrogen bonds with RA89, QA67, KA219 residues from chain A and EB83, KB62, RB163, EB225, KB219 residues of chain B. We conclude that the natural plant metabolite Geraniin can serve as an effective antiviral drug against thymidine kinase enzyme of HSV-1.

1. Schuhmacher, A., Reichling, J., Schnitzler, P. 2003. Virucidal effect of peppermint oil on the enveloped viruses herpes simplex virus type 1 and type 2 in vitro. Phytomedicine. 10(6-7), 504-10.
2. Johnson, R.E., Nahmias, A.J., Magder, L.S., Lee, F.K., Brooks, C.A., Snowden, C.B. 1989. A seroepidemiologic survey of the prevalence of herpes simplex virus type 2 infection in the United States. The New England Journal of Medicine. 321(1), 7-12.
3. Sozen, E., Avunduk, A. M., Akyol, N. 2006. Comparison of efficacy of oral valacyclovir and topical acyclovir in the treatment of herpes simplex keratitis: a randomized clinical trial. Chemotherapy. 52(1), 29-31.
4. Kimberlin, D. W., Whitley, R. J.1998. Human herpesvirus-6: neurologic implications of a newly-described viral pathogen. J Neurovirol. 4(5), 474-85.
5. Reeves,W.C., Corey, L., Adams, H.G., Vontver, L.A., Holmes, K.K. 1981. Risk of recurrence after first episodes of genital herpes. Relation to HSV type and antibody response. N Engl J Med. 305(6), 315-9.
6. Severson, J.L., Tyring, S.K.1999. Relation between herpes simplex viruses and human immunodeficiency virus infections. Arch Dermatol. 135(11),1393-7.
7. Bernard, W., Jindrich, C. 1996. Antiviral therapy of herpes simplex virus infection: recent developments. Eur. Acad. Dermatoi Venereol. 6 ,112-126.
8. Wintersberger, E. 1997. Regulation and biological function of thymidine kinase. Biochem Soc Trans. 25(1), 303-8.
9. Stark, A., Russell, R.B. 2003.Annotation in three dimensions. PINTS: Patterns in Non-homologous Tertiary Structures. Nucleic Acids Res. 31(13), 3341-4.
10. Porter, C.T., Bartlett, G.J., Thornton, J.M. 2004. The Catalytic Site Atlas: a resource of catalytic sites and residues identified in enzymes using structural data. Nucleic Acids Res. 32, D129-33.
11. Laskowski, R.A., Watson, J.D., Thornton, J.M. 2005. ProFunc: a server for predicting protein function from 3D structure. Nucleic Acids Res. 33, W89-93.
12. Laurie, A.T., Jackson, R.M. 2005. Q-SiteFinder: an energy-based method for the prediction of protein-ligand binding sites. Bioinformatics. 21(9), 1908-16.
13. Khan, M.T., Ather, A., Thompson, K.D., Gambari, R. 2005. Extracts and molecules from medicinal plants against herpes simplex viruses. Antiviral Res. 67(2), 107-19.
14. Schneidman-Duhovny, D., Inbar, Y., Nussinov, R., Wolfson, H.J. 2005. PatchDock and SymmDock: servers for rigid and symmetric docking. Nucleic Acids Res. 33,W363-7.
15. Yang, J.M., Chen, C.C. 2004. GEMDOCK: a generic evolutionary method for molecular docking. Proteins. 55(2), 288-304.
16. Morris, G. M., Goodsell, D. S., Halliday, R.S., Huey, R., Hart, W. E., Belew, R. K. and Olson, A. J. 1998. Automated Docking Using a Lamarckian Genetic Algorithm and and Empirical Binding Free Energy Function. J. Computational Chemistry, 19, 1639-1662.
17. Chuanasa, T., Phromjai, J., Lipipun, V., Likhitwitayawuid, K., Suzuki, M., Pramyothin, P., Hattori, M., Shiraki, K. 2008. Anti-herpes simplex virus (HSV-1) activity of oxyresveratrol derived from Thai medicinal plant: mechanism of action and therapeutic efficacy on cutaneous HSV-1 infection in mice. Antiviral Res. 80(1), 62-70.
18. Lipipun, V., Kurokawa, M., Suttisri, R., Taweechotipatr, P., Pramyothin, P., Hattori, M., Shiraki, K. 2008. Efficacy of Thai medicinal plant extracts against herpes simplex virus type 1 infection in vitro and in vivo. Antiviral Res. 60(3), 175-80.
19. Yang, C.M., Cheng, H.Y., Lin, T.C., Chiang, L.C., Lin, C.C. 2007. The in vitro activity of geraniin and 1,3,4,6-tetra-O-galloyl-beta-D-glucose isolated from Phyllanthus urinaria against herpes simplex virus type 1 and type 2 infection. J Ethnopharmacol. 110(3), 555-8.
20. Yang-fei, X., Ying, P., Yi-fei, W. 2008. Current status of natural products from plants as anti-herpes simplex virus 1 agents. Virologica Sinica, 23(5), 305-314.

Herpes simplex virus type-1 Functional site Antiviral compound Acyclovir Geraniin Molecular docking