Identification of Potential Anti‐COVID‐19 Drug Leads from Medicinal Plants through Virtual High‐Throughput Screening

Abstract

AbstractNatural compounds are widely used as attractive and valuable starting points for drug lead discovery. The present study aims to identify phytochemical compounds found in medicinal plants as potential COVID‐19 inhibitors, using ensemble docking simulations. To this end, a phytochemical library from the PHCD database – a database of natural chemical compositions of Persian medicinal herbs (https://persianherb.com) – have been virtually screened against four key protein targets in the SARS‐CoV‐2 life cycle – the Mpro and PLpro proteases and the Spike and human ACE2 proteins. Several potential antiviral lead candidates have been identified based on the “Computational Multitarget Screening” approach, in which favourite candidates interact simultaneously with all four targets. Four of the bioactive phytochemicals identified – Chelidimerine, Gallagyldilacton, Hinokiflavone, and Physalin Z – show the highest binding affinities to all the targets and are suggested to be the best choices for drug design research. Also, several important medicinal plants, including Chelidonium majus L., Punica granatum, Rhus coriaria, Capparis spinose, Cichorium intybus, and Cynara scolymus, with the most phytochemicals interacting with all the host and viral proteins, have been identified that can be considered as the most important herbal resources for drug development with the medicinal plant formulations against COVID‐19.