ABSTRACT
Despite the social distancing and hygiene rules prescribed by the WHO, the novel Corona-virus is still on the way of a significant rapid rise in deaths. Therefore, identification of chemotherapeutic drugs against Corona Viral Infection all around the world is still requires. Some medicinal plants have a valuable therapeutic effect when mixt with honey, the obtained formulations are preliminary use in Cameroon against viral infection particularly respiratory infections. In this work, we looked for the potential anti-SARS-CoV-2 molecule throw execution of in silico computational studies of six Cameroonian plants intervening in the treatment respiratory infections in apiphytotherapy. AutoDock Vina was used for docking studies against SARS-CoV-2 main protease (Mpro) and spike (SP) proteins. We further conducted of pharmacokinetics properties and the safety profile of compounds with the top score in order to identify the best drug candidates. Totally 100 compounds were screened, of these, eighteen showed high binding affinity against SARS-CoV-2 Mpro and SP. The results suggest the effectiveness of compounds 10 and 17 obtained from Citrus Sinensis as potent drugs against SARS-CoV-2 as they tightly bind to its Mpro and SP with low binding energies. The stability of the two compounds complexed with Mpro and SP was validated through MD simulation. The availability of potent protein inhibitors and diverse of compounds from Cameroon flora scaffolds indicate the feasibility of developing potent Mpro and SP proteins inhibitors as antivirals for COVID-19. Based on further in vivo and in vitro experiments and clinical trials, some of these phytoconstituents could be proposed for effective inhibition of the replication of the SARS-CoV-2.
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.