Screening of Natural Compounds as Inhibitor of M^pro SARS-CoV-2 Protein; A Molecular Dynamics Approach

Title:Screening of Natural Compounds as Inhibitor of M^pro SARS-CoV-2 Protein; A Molecular Dynamics Approach

Volume: 31 Issue: 7

Author(s): Anum Javaid, Nousheen bibi, Malik Siddique Mahmood, Hina Batool, Sana Batool, Arslan Hamid, Mahjabeen Saleem, Naeem Mahmood Ashraf*, Tayyaba Afsar, Ali Almajwal and Suhail Razak*

Affiliation:

• School of Biochemistry and Biotechnology, University of the Punjab, Lahore, Pakistan

• Department of Community Health Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia

Keywords: COVID-19, natural anti-viral compounds, immunomodulatory, anti-inflammatory, antioxidant properties, SARS-CoV-2.

Abstract:

Background: New strains of SARS-CoV-2 are continually emerging worldwide. Recently, WHO warned of a severe new wave in Europe. Current vaccines cannot fully prevent reinfection in vaccinated individuals.

Aim: Given this issue, recent research focuses on new antiviral candidates with high efficacy and minimal side effects.

Objectives: Screen natural compounds as inhibitors of M^pro SARS-CoV-2 protein using molecular dynamics.

Methods: In this study, we have screened the potential of plant-based natural anti-viral compounds. A library of the 579 compounds was generated using currently available literature and online databases. All these compounds were screened based on their binding affinities as predicted by molecular docking analysis and compounds having binding affinity values ≤ -10 Kcal/mol were considered for analysis. Furthermore, from physicochemical assessment, drug-likeness initially nine compounds were identified as the antiviral targets for the selected viral proteins. After ADMET analysis and simulations, the compound 9064 with the lowest RMSD, Coul-SR interaction energy (-71.53 kJ/mol), and LJ-SR energy (-95.32 kJ/mol) was selected as the most stable drug candidate against COVID-19 main protease M^pro.

Results: The ΔG value, calculated using MMGBSA also revealed strong binding of the compound with M^pro. The selected antiviral compound 9064 is an antioxidant flavonoid (Catechin or Cianidanol), which was previously known to have significant immunomodulatory, anti-inflammatory, and antioxidant properties.

Conclusion: Considering the limitations of currently available vaccines, our study may provide new insight into potential drugs that may prevent SARS-CoV-2 infection in humans.

Cite this article as:

Javaid Anum, bibi Nousheen, Mahmood Siddique Malik, Batool Hina, Batool Sana, Hamid Arslan, Saleem Mahjabeen, Ashraf Mahmood Naeem*, Afsar Tayyaba, Almajwal Ali and Razak Suhail*, Screening of Natural Compounds as Inhibitor of M^pro SARS-CoV-2 Protein; A Molecular Dynamics Approach, Current Pharmaceutical Design 2025; 31 (7) . https://dx.doi.org/10.2174/0113816128315762240828052002