Identification of possible SARS-CoV-2 main protease inhibitors: in silico molecular docking and dynamic simulation studies

Abstract

Abstract Background COVID-19 was declared a pandemic by the World Health Organisation in 2020 after its outbreak in December 2019 in Wuhan, China. Since researchers have been working to develop specific drugs to cure COVID-19. COVID-19 is caused by the severe acute respiratory cornonavirus2 or popularly known as SARS-CoV2 attacking the ACE2 receptor in the human respiratory system. The main protease translated by the viral genome is a highly conserved protein that plays a crucial role in viral protein replication and transcription. Compounds such as Darunavir and danoprevir have been tested to show potential biological activity against the viral protein, but a high mutation rate defies a permanent solution to this problem. Results In this study, virtual screening of natural ligands (around 170,000 molecules) and FDA-approved repurposed drugs retrieved from ZINC Database was carried out against SARS-CoV2 main protease (PDB ID: 7DJR). Molecular coupling was performed for the top three ligands, where ZINC70699832 showed a significantly good binding affinity of − 11.05 kcal/mol. It has shown an interaction affinity for the residues THR-25, PHE-140, LEU-141, ASN-142, GLY-143, SER-144, CYS-145, MET-165, GLU-166, GLN-189 and GLN-192. The molecular dynamic simulation was also performed using GROMACS, for all complexes where the ZINC70699832–7DJR complex showed stability in terms of root mean square deviation. Conclusion The study recommends that ZINC70699832 has great potential to serve as a potent inhibitor of the main protease of SARS-CoV2 main protease.