Exploring the Therapeutic Potential of L. Phytochemicals: A Computational Study on Inhibiting SARS-CoV-2's Main Protease (Mpro)

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2024 Jun 19

PMID 38893400

Authors

Md Ahad Ali

Humaira Sheikh

Muhammad Yaseen

Md Omar Faruqe

Ihsan Ullah

Neeraj Kumar

Mashooq Ahmad Bhat

Md Nurul Haque Mollah

Affiliations

Soon will be listed here.

Abstract

The outbreak of SARS-CoV-2, also known as the COVID-19 pandemic, is still a critical risk factor for both human life and the global economy. Although, several promising therapies have been introduced in the literature to inhibit SARS-CoV-2, most of them are synthetic drugs that may have some adverse effects on the human body. Therefore, the main objective of this study was to carry out an in-silico investigation into the medicinal properties of L. ( L.)-mediated phytocompounds for the treatment of SARS-CoV-2 infections since phytochemicals have fewer adverse effects compared to synthetic drugs. To explore potential phytocompounds from L. as candidate drug molecules, we selected the infection-causing main protease (Mpro) of SARS-CoV-2 as the receptor protein. The molecular docking analysis of these receptor proteins with the different phytocompounds of L. was performed using AutoDock Vina. Then, we selected the three top-ranked phytocompounds (myricitrin, engeletin, and astilbin) as the candidate drug molecules based on their highest binding affinity scores of -8.9, -8.7 and -8.3 (Kcal/mol), respectively. Then, a 100 ns molecular dynamics (MD) simulation study was performed for their complexes with Mpro using YASARA software, computed RMSD, RMSF, PCA, DCCM, MM/PBSA, and free energy landscape (FEL), and found their almost stable binding performance. In addition, biological activity, ADME/T, DFT, and drug-likeness analyses exhibited the suitable pharmacokinetics properties of the selected phytocompounds. Therefore, the results of this study might be a useful resource for formulating a safe treatment plan for SARS-CoV-2 infections after experimental validation in wet-lab and clinical trials.

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