Screening of cryptogamic secondary metabolites as putative inhibitors of SARS-CoV-2 main protease and ribosomal binding domain of spike glycoprotein by molecular docking and molecular dynamics approaches

The unprecedented quick spreading of newly emerged SARS-CoV-2, the virus responsible for causing COVID-19 has put the whole world in vast crisis. Several prophylactic interventions are being performed to discover the effective anti-COVID-19 agent. Thus, the present study aims to identify the cryptogamic secondary metabolites (CSMs) as potent inhibitors of two major targets of SARS-Cov2, namely 3-chymotrypsin-like protease (3CL(Pro)) and receptor-binding domain (RBD) of spike glycoprotein (SGP), by implementing a computational approach. Molecular docking was carried out on Autodock 4.2 software with the 3CL(Pro) (PDB ID:6LU7) and RBD of SGP (PDB ID:6W41) of the virus. Lopinavir and Arbidol were taken as positive controls to compare the efficacy of randomly selected 53 CSMs. The drug-likeness and pharmacokinetics properties of all metabolites were accessed to discern the anti-COVID 19 activity acting well at the physiological conditions. The docking results predicted that Marchantin E and Zeorin would potentially block the catalytic site of 3CL(Pro) with the interaction energy values of -8.42 kcal/mol and 9.04 kcal/mol, respectively. In addition, Usnic acid revealed its ability to combat the interaction of RBD of SGP to angiotensin-converting enzyme-2 in docking analysis. To certify the potent metabolites for both targets of SARS-CoV-2, MD analysis was performed for 100 ns. The results confirmed that Marchantin E could inhibit SARS-CoV-2 3CL(Pro) and RBD of SGP as well as reveals excellent pharmacokinetic properties. The present study suggests that the identified CSMs could be quickly positioned for further experimental validation to propose promising inhibitors of SARS-CoV-2. (C) 2021 Elsevier B.V. All rights reserved.

Automated summary

The study aims to identify potential inhibitors of SARS-CoV-2 through computational evaluation of cryptogamic secondary metabolites. Some metabolites were found to potentially block the virus's major targets, showing promise as inhibitors.