MOLECULAR DOCKING STUDIES OF CARPROFEN ANALOGUES AGAINST SARSCOV-2 MAIN PROTEASE (Mpro) FOR NOVEL COVID-19 DRUG DISCOVERY

Abstract

MSARSCoV-2 main protease is a homodimer protein that cleaves polyproteins into several non-structural proteins, thus facilitates viral replication and transcription. Viral replication can be blocked potentially when the activity of this enzyme is inhibited. This benefit makes the enzyme an important site for antiviral drug against COVID-19. There are several inhibitors of main protease (Mpro) which have been approved as antiviral drugs but their application is associated with adverse side effects. These side effects are primarily attributed to the less selectivity of the drugs for the main protease (Mpro). Therefore, the development of selective SARSCoV-2 Mpro inhibitors could be a useful technique for finding new viral drugs that are clinically safer. In this study we have shown molecular docking of 272 similar structures of carprofen with the Mpro. Carprofen is a non-steroidal medication with antiviral properties against SARSCoV-2 Mpro. The library of carprofen analogs was screened for effective inhibitors of Mpro and top 100 best scoring ligands were selected to dock with Mpro. Molecular studies showed that carprofen analogs have selective affinity for Mpro. Three such ligands with mseq 95, 94, 45 were selected which had high binding affinity as compared to control ligands (11b).The docking scores of compounds with mseq 95, 94, 45 in Mpro were –6.9380,-6.8877 and -6.6768 respectively. Further analysis of the ligand-protein interactions revealed that these compounds are involved in a number of interactions with Mpro which gives them better binding affinity with Mpro. The compounds are linked with different amino acid residues of Mpro by different types of intermolecular forces. The specific inhibitory activity of these compounds can be confirmed further by invivo and invitro methods leading to the development of safer anti-viral drugs.