Structure-based virtual screening of novel natural products as chalcone derivatives against SARS-CoV-2 M^pro

Abstract

Coronavirus disease 2019 (COVID-19), which is caused by SARS-CoV-2, has spread quickly around the world, causing a global pandemic. It has infected more than 500 million people as of April 28, 2022. Much research has been reported to stop the virus from spreading, but there are currently no approved medicines to treat COVID-19. In this work, a dataset of 142 natural products collected from various medicinal plants was used to perform structure-based virtual screening (SBVS) through the combined application of molecular docking and molecular dynamics (MD) simulation methods. First, the dataset of compounds was optimized using the density functional theory (DFT) approach. The optimized compounds were then submitted to the first screening, which was done by the pKCM web server to look for drug-likeness and the PyRx to look for binding affinity. Among the 142 natural substances, 10 compounds were selected for docking validation. Compounds that interact with CYS145 and LEU141, the essential catalytic residues, as well as compounds with binding affinities less than −8.0 kcal/mol, are considered promising anti-SARS-CoV-2 drug candidates. The top-ranked compounds were then evaluated by MD simulations and MM-GBSA method. These results could help researchers come up with new natural compounds that could be used to treat SARS-CoV-2.

Communicated by Ramaswamy H. Sarma

Keywords:

• COVID-19
• SARS-CoV2
• Natural products
• DFT study
• SBVS approaches

Disclosure statement

No potential conflict of interest was reported by the authors.

Availability of data and material

All data required for evaluating the resources described in this manuscript are contained in the supplementary material.

Code availability

No specific code was generated for analysis of these data.

Authors’ contributions

A. E and F. K: Writing, data set collection, methodology and software; A. O and M. B: Visualization and interpretations of results. All authors made substantial contributions through discussions of ideas, as well as commenting and polishing of the manuscript.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.