Molecular Modeling and Docking Study on Glycoproteins of Tomato Spotted Wilt Virus and its Inhibition by Antiviral Agents

Tomato Spotted Wilt Virus (TSWV) belongs to the genus Tospovirus and has a tripartite, single-stranded negative-sense RNA genome. It is the only genus infects plants in the Bunyaviridae family. During viral infection, a complementary strand code for the envelope glycoprotein (GP) precursor is post-translationally cleaved into two spikes or glycoproteins such as GN (amino-terminal) and GC (carboxyl- terminal). Importantly, GN and GC plays key role in particle assembly, maturation, and release in infected cells. Among the two proteins, GN is most important because during maturation process GC retained in the endoplasmic reticulum (ER) unless co-expressed with GN. It enables GN-GC co-migration from ER to the golgi complex. In order to elevate the broad spectrum of viral inhibitors, it is necessary to understand the viral proteins structural details and its interaction with antiviral drugs. The compounds used for protein-ligand docking are tunicamycin, distamycin-A, tiazofurin, actigard, admire, and ribavirin. In order to elucidate their structural interaction, the three-dimensional structure of both GN and GC was predicted. Protein-protein (GC-GN) docking indicates that the C-terminal of GN is necessary for heterodimerization with GC and localization from ER to golgi complex. Consequently, protein-ligand (GN-antiviral compounds) showed that the compounds such as tunicamycin and distamycin-A were considered as the most efficient drugs. On conclusion, in this study the structural details and the docking interaction between GC-GN and GN-antiviral compounds have been explored in TSWV.