Structurally modified compounds of hydroxychloroquine, remdesivir and tetrahydrocannabinol against main protease of SARS-CoV-2, a possible hope for COVID-19: Docking and molecular dynamics simulation studies

Now a days, more than 200 countries faces the health crisis due to epidemiological disease COVID-19 caused by SARS-CoV-2 virus. It will cause a very high impact on world's economy and global health sector. Earlier the structure of main protease (M-pro) protein was deposited in the RCSB protein repository. Hydroxychloroquine (HCQ) and remdesivir were found to effective in treatment of COVID-19 patients. Here we have performed docking and molecule dynamic (MD) simulation study of HCQ and remdesivir with M-pro protein which gave promising results to inhibit M-pro protein in SARS-CoV-2. On the basis of results obtained we designed structurally modified 18 novel derivatives of HCQ, remdesivir and tetrahydrocannabinol (THC) and carried out docking studies of all the derivatives. From the docking studies six molecules DK4, DK7, DK10, DK16, DK17 and DK19 gave promising results and can be use as inhibitor for M-pro of SARS-CoV-2 to control COVID-19 very effectively. Further, molecular dynamics simulation of one derivative of HCQ and one derivative of tetrahydrocannabinol showing excellent docking score was performed along with the respective parent molecules. The two derivatives gave excellent docking score and higher stability than the parent molecule as validated with molecular dynamics (MD) simulation for the binding affinities towards M-pro of SARS-CoV-2 thus represented as strong inhibitors at very low concentration. (C) 2021 Elsevier B.V. All rights reserved.