In-silico approach to designing effective antiviral drugs against SARS-CoV-2 and SARS-CoV-1 from reported phytochemicals: a quality improvement study

Fatema- Tuz-Zohura; Abu R Md Shawon; Md Maruf Hasan; Abdullah Aeyas; Faisal I Chowdhury; Mayeen U Khandaker

doi:10.1097/MS9.0000000000000839

In-silico approach to designing effective antiviral drugs against SARS-CoV-2 and SARS-CoV-1 from reported phytochemicals: a quality improvement study

Ann Med Surg (Lond). 2023 Jun 8;85(7):3446-3460. doi: 10.1097/MS9.0000000000000839. eCollection 2023 Jul.

Authors

Fatema- Tuz-Zohura¹, Abu R Md Shawon¹, Md Maruf Hasan¹, Abdullah Aeyas¹, Faisal I Chowdhury¹, Mayeen U Khandaker^{2

3}

Affiliations

¹ Department of Chemistry, University of Chittagong, Chittagong.
² Department of General Educational Development, Faculty of Science and Information Technology, Daffodil International University, Dhaka, Bangladesh.
³ Centre for Applied Physics and Radiation Technologies, School of Engineering and Technology, Sunway University, Bandar Sunway, Selangor, Malaysia.

Abstract

Computer-aided drug design by molecular docking, statistical analysis like multiple linear regression (MLR), principal component analysis (PCA), and molecular dynamics studies can emerge as an efficient approach to designing promising core scaffolds for coronavirus medication. The main protease [3-chymotrypsin-like protease (3CL^pro)] of severe acute respiratory syndrome coronavirus (SARS-CoV)-1 and SARS-CoV-2 is one of the critical targets for designing and developing broad-spectrum antiviral therapeutic drugs. The main objective of this study was to investigate potential phytochemicals against SARS-CoV-1 and SARS-CoV-2 to ensure effective natural product-induced therapy. In this evaluation, we have selected 40 reported phytochemicals to design efficient core scaffolds that can act as potent inhibitors against the main proteases of SARS-CoV-2 and SARS-CoV-1. We categorized the selected phytochemicals into a more bioavailable and less bioavailable set, considering phytochemical drug likeliness properties. All the selected phytochemicals vigorously interacted with the catalytic dyads His41 and Cys145. Statistical analysis by MLR confirmed their contribution to structural features on binding affinities and PCA analysis for structural activity relationships for their structural pattern recognition to determine the core scaffold inhibitors. We confirmed that 4'-Hydroxyisolonchocarpin and BrussochalconeA were safe and exhibited excellent pharmacological properties. Because 4'-Hydroxyisolonchocarpin and BrussochalconeA are flavonoid derivatives, they exhibit the chalcone's ring. The presence of the reactive α,β-unsaturated system in the chalcone's rings showed different potential pharmacokinetics with an insignificant toxicological profile. Our comprehensive computational and statistical analysis reveals that these selected phytochemicals (4'-Hydroxyisolonchocarpin, BrussochalconeA) can be used to design potential broad antiviral inhibitors against SARS-CoV-2 and SARS-CoV-1.

Keywords: MM/GBSA (molecular mechanics/generalized Born surface area); molecular dynamics simulation; multiple linear regression; phytochemicals; scaffolds-based drug design; severe acute respiratory syndrome coronavirus-2.