Design and in silico study of the novel coumarin derivatives against SARS-CoV-2 main enzymes

Abstract

The novel coronavirus (SARS-CoV-2) causes severe acute respiratory syndrome and can be fatal. In particular, antiviral drugs that are currently available to treat infection in the respiratory tract have been experienced, but there is a need for new antiviral drugs that are targeted and inhibit coronavirus. The antiviral properties of organic compounds found in nature, especially coumarins, are known and widely studied. Coumarins, which are also metabolites in many medicinal drugs, should be investigated as inhibitors against coronavirus due to their pharmacophore properties (low toxicity and high pharmacokinetic properties). The easy addition of substituents to the chemical structures of coumarins makes these structures unique for the drug design. This study focuses on factors that increase the molecular binding and antiviral properties of coumarins. Molecular docking studies have been carried out to five different proteins (Spike S1-subunit, NSP5, NSP12, NSP15, and NSP16) of the SARS-CoV-2 and two proteins (ACE2 and VKORC1) of human. The best binding scores for 17 coumarins were determined for NSP12 (NonStructural Protein-12). The highest score (–10.01 kcal/mol) in the coumarin group is 2-morpholinoethan-1-amine substituted coumarin. Molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) analyses of selected ligand-protein complexes were performed. The binding energies in each 5 ns were calculated and it was found that the interaction between ligand and target protein were stable.

Communicated by Ramaswamy H. Sarma

Keywords:

• Coronavirus
• SARS-CoV-2
• MM-PBSA
• coumarin
• molecular docking
• drug design

Acknowledgments

The numerical calculations reported in this paper were fully performed at TUBITAK ULAKBIM, High Performance, and Grid Computing Center (TRUBA resources). We thank MNG Holding for their support. In this study, machinery and equipment obtained from the RGD-020 project of Sivas Cumhuriyet University Scientific Research Project Directorate were used in MM-PBSA Analyses. For this reason, we thank Sivas Cumhuriyet University Scientific Research Project Directorate.

Disclosure statement

No potential conflict of interest is reported by the authors.