Natural furin inhibitor(s) as potent therapeutic molecule to mitigate SARS-CoV-2 infection

Abstract

The COVID 2019 has had been going pandemic as per WHO situation reports. The major differentiating point in this virus is the presence of a unique furin cleavage site. Our insilico study points out to the effectiveness of a potent plant origin furin inhibitor. We exploited the aspect of the cleavage machinery of furin subunits which is critical and indispensible to the entry of SARS-CoV-2 in human cells and subsequent massive contagion. In-silico analysis was done to observe the interactions of proposed analogs of protease inhibitor of plant origin against furin protein as well as the furin spike glycoprotein (SGP) binding machinery. This was done by docking protocols using Hex 6.0 software followed by molecular Dynamic simulation (MDS) analysis in 100 ns scale using Amber94. Further, the images were analysed with PyMol software. The analogs I, II and III included in our study showed strong interactivity against furin individually, as well as the furin-Spike Glycoprotein 1 binding machinery. The findings were confirmed using molecular dynamic simulation analysis which indicated good structural stability and ability to neutralise furin and furin-spike glycoprotein 1. Analog II was found to be the best interactive molecule against furin, showing the least deviation (1.484 ± 0.0064). Also, it was the most effective against furin + Spike glycoprotein I machinery [1.575 ± 0.01]. We report the first of its kind of natural furin inhibitor(s) which would disrupt the furin machinery of SARS-CoV-2 and help in controlling the COVID-19 contagion. Communicated by Ramaswamy H. Sarma