In silico drug discovery of novel small lead compounds targeting nipah virus attachment glycoprotein

Abstract

Introduction: Nipah virus (NiV) and Hendra virus are the type species of the highly pathogenic paramyxovirus genus Henipavirus, which can cause severe respiratory disease and fatal encephalitis infections in humans. NiV contains two envelope glycoproteins, the receptor-binding G glycoprotein (NiV-G) that facilitates attachment to host cells and the fusion (F) glycoprotein that mediates membrane merger. The attachment glycoprotein (NiV-G) on the surface of the virus is an important virulent factor and a promising antiviral target. In vitro, favipiravir inhibited Nipah and Hendra virus replication and transcriptionat micro molar concentrations. Experimental: In this study, we had designed ten bioisosteres of favipiravir containing pyrazine or quinoxaline moeity to identify novel inhibitors of Nipah virus using different in silico methods. The molecular docking studies were performed using iGEMDOCK2.1. Drug likeness of the compounds was predicted using SwissADME online tool. In silico toxicity studies were performed using ProTox-II. The comparison of in silico results were done with standard drug favipiravir. Results: In the docking studies, eight compounds showed significant inhibitory activity with low docking score as compare to standard drug. All the designed molecules had drug likeness properties and predicted to be nontoxic. Conclusion: These findings indicate that the novel bioisosteres of favipiravir have promising potential to target NiV-G/ephrin interactions to disrupt viral entry and provide the foundation for structure-based antiviral drug design.