ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Novel Molecules derived from 3-O-(6-galloylglucoside) inhibit Main Protease of SARS-CoV 2 In Silico

Haruna Isiyaku Umar, Adeola Ajayi, Ridwan Opeyemi Bello, Hafsat Olateju Alabere, Afees Akinbode Sanusi, Olamide Olusegun Awolaja, Mohammed Mansour Alshehri, and Prosper Obed Chukwuemeka

Department of Biochemistry, School of Life Sciences, Federal University of Technology, Akure, Nigeria

E-mail: uhumar@futa.edu.ng

Received: 22 July 2021  Accepted: 21 September 2021

Abstract:

The ongoing pandemic caused by the severe acute respiratory syndrome 2 (SARS-CoV 2) has led to more than 168 million confirmed cases with 3.5 million deaths as at 28th May, 2021 across 218 countries. The virus has a cysteine protease called main protease (Mpro) which is significant to it life cycle, tagged as a suitable target for novel antivirals. In this computer-assisted study, we designed 100 novel molecules through an artificial neural network-driven platform called LigDream (https://playmolecule.org/LigDream/) using 3-O-(6-galloylglucoside) as parent molecule for design. Druglikeness screening of the molecules through five (5) different rules was carried out, followed by a virtual screening of those molecules without a single violation of the druglike rules using AutoDock Vina against Mpro. The in silico pharmacokinetic features were predicted and finally, quantum mechanics/molecular mechanics (QM/MM) study was carried out using Molecular Orbital Package 2016 (MOPAC2016) on the overall hit compound with controls to determine the stability and reactivity of the lead molecule. The findings showed that eight (8) novel molecules violated none of the druglikeness rules of which three (3) novel molecules (C33, C35 and C54) showed the utmost binding affinity of −8.3 kcal/mol against Mpro; C33 showed a good in silico pharmacokinetic features with acceptable level of stability and reactively better than our controls based on the quantum chemical descriptors analysis. However, there is an urgent need to carry out more research on these novel molecules for the fight against the disease.

Keywords: 3-O-(6-galloylglucoside); Artificial neural network-driven platform; LigDream; Main protease; Novel compounds; Quantum mechanics; SARS-CoV 2

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-021-01899-y

Chemical Papers 76 (2) 785–796 (2022)