Discovery of Natural Compounds and Derivatives with Inhibitory Activity against NS2B/NS3 Serine Protease of Zika Virus by Computational Approaches

Abstract

Zika virus (ZIKV) belongs to the Flavivirus genus primarily transmitted by Aedes mosquito. There have been reports of an association of child disorders among infected women during pregnancy. To date, there is no drug or vaccine that can directly combat ZIKV infection. Therefore, the design and development of effective drugs are extremely needed. Specifically, the targeted protein of this virus is NS2B/NS3 serine protease, which is an enzyme important for viral replication. In this study, we have used computational chemistry approaches including molecular docking and molecular dynamic (MD) simulation to screen and study binding interactions between protein and 7 groups of natural compounds at allosteric site. The groups of natural compounds include chalcone, flavonoid, iodovinyl sulfones, sulfonylated indeno quinolones, vinyl sulfones, quinolinone and nitroolefin. Moreover, binding free energy calculation based on the MM/GBSA method showed that DNO71_f belonging to flavonoid category exhibited the highest binding affinity to ZIKV protease (-17.17±1.90 kcal/mol). Therefore, the results presented here suggested that DNO71_f can be used for further design of drug that effectively inhibits the NS2B/NS3 serine protease of ZIKV.