Screening of plant-based natural compounds as a potential COVID-19 main protease inhibitor: anin silicodocking and molecular dynamics simulation approach

A new strain of coronavirus (CoV) has been identified as SARS-CoV-2, which is responsible for the recent COVID-19 pandemic. Currently, there is no approved vaccine or drug available to combat the pandemic. COVID-19 main protease (M-pro) is a key CoV enzyme, which plays an important role in triggering viral replication and transcription, turns it into an attractive target. Therefore, we aim to screen natural products library to find out potential COVID-19 M(pro)inhibitors. Plant-based natural compounds from Sigma-Aldrich plant profiler chemical library have been screened through virtual molecular docking and molecular dynamics simulation to identify potential inhibitors of COVID M-pro. Our virtual molecular docking results have shown that there are twenty-eight natural compounds with a greater binding affinity toward the COVID-19 M(pro)inhibition site as compared to the co-crystal native ligand Inhibitor N3 (-7.9 kcal/mol). Also, molecular dynamics simulation results have confirmed that Peonidin 3-O-glucoside, Kaempferol 3-O-beta-rutinoside, 4-(3,4-Dihydroxyphenyl)-7-methoxy-5-[(6-O-beta-D-xylopyranosyl-beta-D-glucopyranosyl)oxy]-2H-1-benzopyran-2-one, Quercetin-3-D-xyloside, and Quercetin 3-O-alpha-L-arabinopyranoside (selected based on the docking score) possess a significant amount of dynamic properties such as stability, flexibility and binding energy. OurIn silcoresults suggests that all the above mention natural compounds have the potential to be developed as a COVID-19 M(pro)inhibitor. But before that, it must go through under the proper preclinical and clinical trials for further scientific validation. Communicated by Ramaswamy H. Sarma

Automated summary

This study investigates potential inhibitors of COVID-19 M(pro) and screens out several natural compounds through virtual molecular docking and molecular dynamics simulation. The results show that these natural compounds have high binding affinity to COVID-19 M(pro) and possess important dynamic properties such as stability and flexibility. However, further preclinical and clinical trials are needed to validate these compounds.