Structure-based screening of Natural product libraries in search of potential antiviral drug-leads as first-line treatment to Covid-19 infection

Abstract

The study describes a novel strategy to screen natural products (NPs) based on their structural similarities with chemical drugs and their use as first-line treatment to Covid-19 infection. In the present study, the in-house natural product libraries, consisting of a total of 26,311 structures, were screened against potential targets of 2019-nCoV/SARS-CoV-2 based on their structural similarities with the prescribed chemical drugs. The comparison was based on molecular properties, 2 and 3-dimensional structural similarities, activity cliffs, and core fragments of NPs with chemical drugs. The screened NPs were evaluated for their therapeutic effects based on predicted in-silico pharmacokinetic and pharmacodynamics properties, binding interactions with the appropriate targets, and structural stability of the bound complex. The study yielded NPs with significant structural similarities to synthetic drugs currently used to treat Covid-19 infections. The study proposes the selected NPs as Anti-retroviral protease inhibitors, RNA-dependent RNA polymerase inhibitors, and viral entry inhibitors.