In silico validation of coumarin derivatives as potential inhibitors against Main Protease, NSP10/NSP16-Methyltransferase, Phosphatase and Endoribonuclease of SARS CoV-2

Abstract

Coronavirus Disease (COVID-19) is recently declared pandemic (WHO) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The virus was named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), (Coronavirus Disease 2019). Currently, there is no specific drug for the therapy of COVID-19. So, there is a need to develop or find out the new drug from the existing to cure the COVID-19. Identification of a potent inhibitor of Methyltransferase, Endoribonuclease, Phosphatase and Main Protease enzymes of SARS CoV-2 by coumarin derivatives using insilico approach. The in silico studies were performed on maestro 12.0 software (Schrodinger LLC 2019, USA). Two thousand seven hundred fifty-five biologically active coumarin derivative was docked with above receptor proteins of SARS CoV-2. The molecular dynamic simulation of the top one ligand of respected proteins was performed. Top five ligands of each protein were taken for study. Coumarin derivatives actively interact with taken receptors and showed good docking results for Methyltransferase, Endoribonuclease, Phosphatase and Main Protease and top five compounds of each have docking score from –9.00 to –7.97, –8.42 to –6.80, –8.63 to –7.48 and –7.30 to –6.01 kcal/mol, respectively. The docked compounds were showed RMSD and binding stability of simulated ligands are show the potency of ligands against the SARS CoV-2. Our study provides information on drugs that may be a potent inhibitor of COVID-19 infection. Drug repurposing of the available drugs would be great help in the treatment of COVID-19 infection. The combination therapy of the finding may improve inhibitory activity.

Communicated by Ramaswamy H. Sarma

Highlights

• Coronavirus Disease (COVID-19) is recently declared pandemic (WHO) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

• In silico virtual screening, docking, ADME, MM-GBSA and MD simulation analysis of coumarin derivatives against Methyltransferase (MTase), Endoribonuclease(endoU), ADP ribose Phosphatase and Main Protease enzyme of SARS CoV-2.

• All the analysis was performed on Maestro 12.0 Schrodinger software against respective receptors.

• Top five compounds of coumarin derivatives s docked at the active site of Methyltransferase (MTase), Endoribonuclease(endoU), ADP ribose Phosphatase and protease and top five compounds of each have docking score from –9.00 to –7.97, –8.42 to –6.80, –8.63 to –7.48 and –7.30 to –6.01 kcal/mol, respectively, of SARS CoV-2.

• These compounds were used to analysis of binding free energy by using the Prime MM-GBSA module.

• All the compounds showed drug-likeness properties.

• MD simulation of Proteins and ligands showed binding stability and good RMSD, radius of gyration of protein, coulomb-SR and LJ-SR energy.

Keywords:

• SARS CoV-2
• docking
• ADME/T
• binding free energy
• MD simulation
• inhibitor

Acknowledgement

The authors are grateful to the Indian Institute of Information Technology Allahabad for providing Central computing facility and laboratory support to us.

Disclosure statement

No potential conflict of interest was reported by the authors.

Author contributions

Akhilesh Kumar Maurya designed experiments, performed all other experiments and data analysis and prepared the manuscript. Nidhi Mishra guided the study and manuscript preparation.

Additional information

Funding

The authors are grateful to the Ministry of Human Resource Development for funding as research fellowship.