Screening of Potent Phytochemical Inhibitors Against SARS-CoV-2 Main Protease: An Integrative Computational Approach

Shafi Mahmud; Md Robiul Hasan; Suvro Biswas; Gobindo Kumar Paul; Shamima Afrose; Mohsana Akter Mita; Mst Sharmin Sultana Shimu; Maria Meha Promi; Umme Hani; Mohamed Rahamathulla; Md Arif Khan; Shahriar Zaman; Md Salah Uddin; Mohammed Rahmatullah; Rownak Jahan; Ali M Alqahtani; Md Abu Saleh; Talha Bin Emran

doi:10.3389/fbinf.2021.717141

Screening of Potent Phytochemical Inhibitors Against SARS-CoV-2 Main Protease: An Integrative Computational Approach

Front Bioinform. 2021 Oct 5:1:717141. doi: 10.3389/fbinf.2021.717141. eCollection 2021.

Authors

Shafi Mahmud¹, Md Robiul Hasan², Suvro Biswas², Gobindo Kumar Paul¹, Shamima Afrose², Mohsana Akter Mita², Mst Sharmin Sultana Shimu², Maria Meha Promi², Umme Hani³, Mohamed Rahamathulla³, Md Arif Khan⁴, Shahriar Zaman¹, Md Salah Uddin¹, Mohammed Rahmatullah⁴, Rownak Jahan⁴, Ali M Alqahtani⁵, Md Abu Saleh¹, Talha Bin Emran⁶

Affiliations

¹ Department of Genetic Engineering and Biotechnology, Microbiology Laboratory, University of Rajshahi, Rajshahi, Bangladesh.
² Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi, Bangladesh.
³ Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha, Saudi Arabia.
⁴ Department of Biotechnology and Genetic Engineering, University of Development Alternative, Dhaka, Bangladesh.
⁵ Department of Pharmacology, College of Pharmacy, King Khalid University, Abha, Saudi Arabia.
⁶ Department of Pharmacy, BGC Trust University Bangladesh, Chittagong, Bangladesh.

Abstract

Coronavirus disease 2019 (COVID-19) is a potentially lethal and devastating disease that has quickly become a public health threat worldwide. Due to its high transmission rate, many countries were forced to implement lockdown protocols, wreaking havoc on the global economy and the medical crisis. The main protease (M^pro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative virus for COVID-19, represent an effective target for the development of a new drug/vaccine because it is well-conserved and plays a vital role in viral replication. M^pro inhibition can stop the replication, transcription as well as recombination of SARS-CoV-2 after the infection and thus can halt the formation of virus particles, making M^pro a viable therapeutic target. Here, we constructed a phytochemical dataset based on a rigorous literature review and explored the probability that various phytochemicals will bind with the main protease using a molecular docking approach. The top three hit compounds, medicagol, faradiol, and flavanthrin, had binding scores of -8.3, -8.6, and -8.8 kcal/mol, respectively, in the docking analysis. These three compounds bind to the active groove, consisting of His41, Cys45, Met165, Met49, Gln189, Thr24, and Thr190, resulting in main protease inhibition. Moreover, the multiple descriptors from the molecular dynamics simulation, including the root-mean-square deviation, root-mean-square fluctuation, solvent-accessible surface area, radius of gyration, and hydrogen bond analysis, confirmed the stable nature of the docked complexes. In addition, absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis confirmed a lack of toxicity or carcinogenicity for the screened compounds. Our computational analysis may contribute toward the design of an effective drug against the main protease of SARS-CoV-2.

Keywords: SARS-CoV-2; admet; molecular docking; molecular dynamics; phytochemicals.