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Natural Compounds as Inhibitors of SARS-CoV-2 Main Protease (3CLpro): A Molecular Docking and Simulation Approach to Combat COVID-19

preprint
revised on 30.05.2020 and posted on 01.06.2020 by Md Tabish Rehman, Mohamed F AlAjmi, Afzal Hussain

Recently, the emergence and dissemination of SARS-CoV-2 has caused high mortality and enormous economic loss. In the fight against COVID-19, the rapid development of new drug molecules is the need of hour. However, the conventional approaches of drug development is time consuming and expensive in nature. In this study, we have adopted an alternative approach to identify lead molecules from natural sources using high throughput virtual screening approach. Ligands from natural compounds library from Selleck Inc (L1400) have been screened to evaluate their ability to bind and inhibit the main protease (Mpro or 3CLpro) of SARS-CoV-2, which is a potential drug target. We found that Kaempferol, Quercetin, and Rutin were able to bind at the substrate binding pocket of 3CLpro with high affinity (105-106 M-1) and interact with the active site residues such as His41 and Cys145 through hydrogen bonding and hydrophobic interactions. In fact, the binding affinity of Rutin was much higher than Chloroquine (1000 times) and Hydroxychloroquine (100 times) and was comparable to that of the reference drug Remdesivir, which is in clinical trials to treat COVID-19 patients. The results suggest that natural compounds such as flavonoids have the potential to be developed as novel inhibitors of SARS-CoV-2 with a comparable potency as that of Remdesivir. However, their clinical usage on COVID-19 patients is a subject of further investigations and clinical trials.


Funding

Research grant number (RGP-1441-150), Deanship of Scientific Research, King Saud University, Riyadh, Saudi Arabia

History

Email Address of Submitting Author

mrehman@ksu.edu.sa

Institution

King Saud University

Country

Saudi Arabia

ORCID For Submitting Author

0000-0003-2341-900X

Declaration of Conflict of Interest

None to declare

Version Notes

Manuscript_Version2

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