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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.

ABSTRACT: 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.

SUBMITTER: Prateeksha G

PROVIDER: S-EPMC8084107 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:An outbreak of Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has been recognized as a global health concern. Since, no specific antiviral drug is proven effective for treatment against COVID-19, identification of new therapeutics is an urgent need. In this study, flavonoid compounds were analyzed for its inhibitory potential against important protein targets of SARS-CoV-2 using computational approaches. Virtual docking was performed for screening of flavonoid compounds retrieved from PubChem against the main protease of SARS-CoV-2 using COVID-19 docking server. The cut off of dock score was set to >-9 kcal/mol and screened compounds were individually docked against main protease, RNA-dependent RNA polymerase, and spike proteins using AutoDock 4.1 software. Finally, lead flavonoid compounds were subjected to ADMET analysis. A total of 458 flavonoid compounds were virtually screened against main protease target and 36 compounds were selected based on the interaction energy value >-9 kcal/mol. Furthermore, these compounds were individually docked against protein targets and top 10 lead compounds were identified. Among the lead compounds, agathisflavone showed highest binding energy value of -8.4 kcal/mol against main protease, Albireodelphin showed highest dock score of -9.8 kcal/mol and -11.2 kcal/mol against RdRp, and spike proteins, respectively. Based on the high dock score and ADMET properties, top 5 lead molecules such as Albireodelphin, Apigenin 7-(6″-malonylglucoside), Cyanidin-3-(p-coumaroyl)-rutinoside-5-glucoside, Delphinidin 3-O-beta-D-glucoside 5-O-(6-coumaroyl-beta-D-glucoside) and (-)-Maackiain-3-O-glucosyl-6″-O-malonate were identified as potent inhibitors against main protease, RdRp, and spike protein targets of SARS-CoV-2. These all compounds are having non-carcinogenic and non-mutagenic properties. This study finding suggests that the screened compounds include Albireodelphin, Apigenin 7-(6″-malonylglucoside), Cyanidin-3-(p-coumaroyl)-rutinoside-5-glucoside, Delphinidin 3-O-beta-D-glucoside 5-O-(6-coumaroyl-beta-D-glucoside) and (-)-Maackiain-3-O-glucosyl-6″-O-malonate could be the potent inhibitors of SARS-CoV-2 targets.

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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.

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