In Silico Approach for Designing Novel SARS-CoV-2 Inhibitors from Medicinal Plants

ABSTRACT

Several countries in the world, are still under the threat of SARS-CoV-2 propagation, although the majority of the population has received a vaccine. Some ethno-botanical surveys were conducted to document potential herbal remedies that can be used in the management of the COVID-19 pandemic in Cameroon. Medicinal plants belonging to Cameroon flora could be a source for the discovery of potential inhibitors of SARS-CoV-2Mpro and spike proteins. These two proteins play a pivotal role in mediating viral replication and transcription, making them attractive targets for drug design against SARS-CoV-2. The aim of this in silico study is to evaluate the behavior of the isolated secondary metabolites from Cameroonian medicinal plant species towards SARS-CoV-2Mpro and spike proteins. In the present study, six plant species are selected among the frequently used plants to treat COVID-19 and related symptoms in Cameroon. To highlight the interactions of studied secondary metabolites with SARS-CoV-2Mpro (6lu7) and spike (6m0j) proteins a molecular docking analysis is used. Among the one hundred and twenty-five screened compounds, thirty-five showed high binding affinity against the two targeted proteins. Furthermore, molecular dynamics simulations were performed to support the docking results. Additional investigations, including physicochemical properties, pharmacokinetics, and toxicological profile show that only twelve compounds bind tightly to Mpro (6lu7) and spike (6m0j) proteins and could be considered as promising drug candidates of SARS-CoV-2. The selected twelve compounds are evaluated for their acute and chronic toxicity, possible mutagenic, tumorigenic, irritant, and reproductive effectiveness. The outcomes of this study suggest the possibility of developing potent Mpro and spike proteins inhibitors from naturally occurring compounds belonging to Cameroon flora. © 2022,Physical Chemistry Research. All Rights Reserved.