A therapeutic approach to mitigate SARS CoV2 infection using natural
furin inhibitor(s)
Abstract
Purpose: 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. Methods: 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 binding machinery. This was done by docking protocols
using Hex 6.0 software followed by molecular Dynamic simulation (MDS)
analysis in 100ns scale using Amber94. Further, the images were analysed
with PyMol software. Results: 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 (SGP I) machinery [1.575±
0.01]. Major conclusions: We report the first of its kind of
natural furin inhibitor(s) which would disrupt the furin machinery of
SARS CoV2 and help in controlling the CoViD 19 contagion.