Screening, molecular simulation & in silico kinetics of virtually designed covid-19 main protease inhibitors

Mohammed S Aleissa; Mohammed Al-Zharani; Md Saquib Hasnain; Saad Alkahtani

doi:10.1016/j.jksus.2022.102283

Screening, molecular simulation & in silico kinetics of virtually designed covid-19 main protease inhibitors

J King Saud Univ Sci. 2022 Nov;34(8):102283. doi: 10.1016/j.jksus.2022.102283. Epub 2022 Aug 31.

Authors

Mohammed S Aleissa¹, Mohammed Al-Zharani¹, Md Saquib Hasnain², Saad Alkahtani³

Affiliations

¹ Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University, Riyadh, Saudi Arabia.
² Department of Pharmacy, Palamau Institute of Pharmacy, Chianki, Daltonganj 822102, Jharkhand, India.
³ Department of Zoology, College of Science, King Saud University, P. O. Box 2455, Riyadh 11451, Saudi Arabia.

Abstract

Coronavirus (covid-19) infection is considered to be deadliest ever pandemic experienced by the human being. It has very badly affected the socio-economic health of human and stuck the scientific community to think and rethink about its complete eradication. But due to no effective treatment or unavailability of vaccine the health professional could not show any significant improvement to control the pandemic. The situation needs newer molecule, vaccine or effective treatment to control covid-19 infection. Different target in viruses has been explored and proteases enzymes were found to be therapeutically effective target for the design of potential anti-covid-19 molecule as it plays the vital role in viral replication and assembly. Structure-based drug design was employed to discover the small molecule of anti-covid-19. Here we considered the small library of naturally occurring polyphenolic compounds and molecular docking, Molecular dynamics (MD) simulations, free binding energy calculation and in-silico ADME calculations to identify the newer HITs. Based upon their score the two molecules were identified as promising candidate. The docking scores were found to be -7.643 and -7.065 for the HIT1 and HIT-2 respectively. In MD simulations study the RMSD values were found to be 4.3 Å & 4.9 Å respectively. To validate these results MM-GBSA was performed and their binding free energies were computationally determined. The prime energy values of identified HITs (-13412.45 & -13441.8 kJ/mole) were found to be very close proximity to reference molecule (-13493.05 kJ/mole). Then in-silico ADME calculations were performed to calculate the drug likeliness identified HITs. BY considering all the values comparative to reference molecule and obtained in-silico pharmacokinetic properties of identified HITs we can suggest that HIT-1 and HIT-2 would be the most promising molecules that can inhibit the main protease enzyme of covid-19. These two molecules would become the potential drug candidate for the treatment of covid-19 infections.

Keywords: Covid-19; HIT; MD simulation; Phenolic compounds; Protease inhibitor.