Finding a prospective dual-target drug for the treatment of coronavirus disease by theoretical study

Abstract

Spike protein of coronavirus is a key protein in binding and entrance of virus to the human cell via binding to the receptor-binding domain (RBD) domain of S1 subunit to peptidase domain region of ACE2 receptor. In this study, the possible effect of 24 antiviral drugs on the RBD domain of spike protein was investigated via docking and molecular dynamics simulation for finding a dual-target drug. At first, all drugs were docked to the RBD domain of spike protein, and then all complexes and free RBD domains were separately used for molecular dynamics simulation for 50 ns via amber18 software. The simulation results showed that 10 ligands from 28 ligands were separated from the RBD domain, and among 18 remained ligands, baloxavir marboxil, and danoprevir drugs, besides endonuclease activity and protease inhibitory, can bind to key residues of the RBD domain. Then these drugs have a dual target and should be more effective than current drugs, and experimental studies should be done on baloxavir marboxil and danoprevir as more potential drugs for coronavirus disease

Communicated by Ramaswamy H. Sarma

Keywords:

• Coronavirus disease
• spike protein
• docking
• molecular dynamics simulation
• antiviral drugs
• MM/GBSA binding free energy

Acknowledgements

The authors thank Shahrekord University and the National Institute of genetic engineering and Biotechnology (NIGEB) of Iran for funding this project.

Disclosure statement

No potential conflict of interest was reported by the authors.