Unveiling of Potential Zika Virus RNA polymerase Inhibitors Using Structure based Virtual Screening

Abstract

Zika virus (ZIKV) infection has been associated with Guillain-Barre syndrome in adults and Microcephaly in infants. However, there is no currently approved antiviral drug against ZIKV. The 103-kDa NS5 protein is the largest ZIKV protein whose C-terminal portion has RNA-dependent RNA polymerase activity and N-terminal RNA cap-processing activity (methyltransferase domain). Therefore, it is an important target for synthesis/discovery of novel anti-ZIKV drugs. A database consisting of 720 marine and plant derived compounds of South Africa was used for virtual screening against a potential inhibitor binding site of ZIKV’s NS5 protein. All its cataloged compounds were screened for their drug likeliness using Lipinski’s parameters. Thereafter, 200 selected compounds were used for virtual screening for their affinities for the target site. Finally, top 5 ligands were redocked to get a detailed insight into their interaction with conserved amino acids of the target site. An additional screening was mounted to filter out the potential toxic compounds among the top 5 likely candidates by AdmetSAR web-server. Two lead compounds, SANC00235 and SANC00257 fulfilled all the criteria laid down by us. These compounds can be potential candidates for further in vitro and in vivo studies in order to validate their anti-ZIKV activity.