Investigating into the molecular interactions of flavonoids targeting NS2B-NS3 protease from ZIKA virus through in-silico approaches

Abstract

Zika virus (ZIKV), belongs to the flavivirus genus and Flaviviridae family that associated with serious diseased conditions like microcephaly and other neurological disorders (Guillan-Barré syndrome). As there is no vaccine or therapies available against ZIKV to date. Hence, it is an unmet need to find potential drug candidates and target sites against Zika virus infection. NS2B-NS3 protease making an attractive target for therapeutic intervention in ZIKV infections because of its critical role in hydrolysis of a single polyprotein encoded by Zika virus. Recently, there are some experimental evidence about the flavonoids as Zika virus NS2B-NS3 protease inhibitors. However, molecular interaction between protease complex and inhibitors at atomic levels has not been explored. Here, we have taken the experimentally validated thirty-eight flavonoids inhibitors against NS2B-NS3 protease to examine the molecular interaction using molecular docking and molecular dynamics simulations. We found out few flavonoids such as EGCG and its two derivatives, isoquercetin, rutin and sanggenon O showing interaction with catalytic triad (His51, Asp75, and Ser135) of the active site of NS2B-NS3 protease and found to be stable throughout the simulation. Therefore it is evident that interaction with the catalytic triad playing a vital role in the inhibition of the enzyme activity as a result inhibition of the virus propagation. However these compounds can be explored further for understanding the mechanism of action of these compounds targeting NS2B-NS3 protease for inhibition of Zika virus.

Keywords: MD simulations; NS2B-NS3 protease; ZIKA virus; flavivirus; flavonoids; non structural proteins.