Identification of novel phytochemicals from Hibiscus rosa sinensis flower as a prospective inhibitor targeting the 3CLpro enzyme of SARS-CoV-2 using computational approaches.

Abstract

Abstract Hibiscus rosa sinensis has an infinite resource of phytochemicals and has emerged as a solution for different health-related issues such as anti-diabetic, anti-microbial and wound healing activity as proved in past clinical studies. Focusing on the current situation, an incessant increase in daily COVID-19 cases and the struggle to discover effective treatment measures for SARS-CoV-2 had led to a global health catastrophe. Upsurge in COVID-19 cases had revealed a pattern characterised as a first, second, third wave and beyond. This cycle of new SARS-CoV-2 variant transmission needed to be terminated by selecting a favourable effective target, and the 3CL protease enzyme (3CLpro or Mpro) of SARS-CoV-2 acts as a possible target. The objective of this study is to investigate the phytochemicals identified in Hibiscus rosa sinensis flowers for their potential anti-SARS-CoV-2 properties virtually, targeting the 3CLpro or Mpro, which regulates viral pathogenesis. The present research protocol includes molecular docking of 34 phytochemicals identified from the Hibiscus rosa sinensis flower and targeted against the active site of the 3CLpro enzyme. Computational analysis revealed that the top 3 ligands: cyanidin-3-sophoroside-5-glucoside (-10.9 kcal/mol), 1,2-benzenedicarboxylic acid isodecyl octyl ester (-10.1 kcal/mol) and rutin (-9.3 kcal/mol) had better binding affinity as compared to the control inhibitor remdesivir (-8 kcal/mol). Further investigation in terms of ligand-protein interaction, physiochemical, ADMET and drug-likeness parameters showed that cyanidin-3-sophoroside-5-glucoside possessed promising properties and could act as a potentially effective drug candidate. However, our study needs to be supported by in vitro and in vivo evaluations to determine the precise mechanism of inhibitory action.