Molecular modeling identification of potential drug candidates from selected African plants against SARS-CoV-2 key druggable proteins

Coronavirus disease 2019 (COVID-19) pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is one of the major health threats the world has experienced. In order to stem the tide of the virus and its associated disease, rapid ef-forts have been dedicated to identifying credible anti-SARS-CoV-2 drugs. This study forms part of the continuing effort s to develop anti-SARS-CoV-2 molecules and employed a com-putational structure-activity relationship approach with emphasis on 99 plant secondary metabolites from eight selected African medicinal plants with proven therapeutic benefits against respiratory diseases focusing on the viral protein targets [Spike protein (Sgp), Main protease (Mpro), and RNA-dependent RNA polymerase (RdRp)]. The results of the molecu-lar dynamics simulation of the best docked compounds presented as binding free energy revealed that three compounds each against the Sgp (VBS, COG and ABA), and Mpro (COR, QOR and ABG) had higher and better affinity for the proteins than the respective refer-ence drugs, cefoperazone (CSP) and Nelfinavir (NEF), while four compounds (HDG, VBS, COR and KOR) had higher and favorable binding affinity towards RdRp than the refer-ence standard, ramdesivir (RDS). Analysis of interaction with the receptor binding domain amino acid residues of Sgp showed that VBS had the highest number of interactions (17) relative to 14 and 13 for COG and ABA, respectively. For Mpro, COR showed interactions with catalytic dyad residues (His172 and Cys145). Compared to RDS, COR, HDG, VBS and KOR formed 19, 18, 17 and 12 H-bond and Van der Waal bonds, respectively, with RdRp. Furthermore, structural examination of the three proteins after binding to the lead com-pounds revealed that the compounds formed stable complexes. These observations suggest that the identified compounds might be beneficial in the fight against COVID-19 and are suggested for further in vitro and in vivo experimental validation.(c) 2022 The Authors. Published by Elsevier B.V. on behalf of African Institute of Mathematical Sciences / Next Einstein Initiative. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

Automated summary

This study focuses on the identification of potential anti-SARS-CoV-2 compounds from African medicinal plants and demonstrates their binding affinity to viral protein targets. These compounds show promising results and could be further validated through in vitro and in vivo experiments.