Targeting SARS-CoV2 Main Protease using HTVS and simulation analysis: A drug repurposing approach against COVID-19

Coronavirus pandemic COVID-19 has caused a wide range of harm worldwide with its inception in December 2019 in Wuhan, China. To date, there is no promising drug identified for the treatment of the disease. In view of this, scientists have elucidated X-ray structures of the proteins in the SARS-CoV 2 virus. These can act as probable drug targets for the design of drugs ,what is an urgent need. One of the main proteins of the virus is its main protease Mpro, which is responsible for producing polyproteins of the virus. In this study, we have used the main protease as the target for drug design and repurposing for COVID-19. Two approaches were applied in order to develop a fast and effective treatment against the virus. The first approach was drug repurposing through in silico docking analysis of existing FDA-approved drugs and the second approach was high throughput screening of molecules from the ZINC database against the main protease. Two docking protocols - a fast docking algorithm to screen the hits or lead molecules and simulation-based molecular dynamics docking procedure to optimize the obtained hits were utilized. We could observe a definite scaffold-based binding affinity against the main protease. These scaffolds were lutein, steroids, morphine and quinolone, CPT. Thiotepa was identified as the best-docked molecule with the highest binding affinity. Unique molecules like lutein, beta carotene, Buprenorphine, etc were identified as promising hits, which can be used as repurposed drugs against SARS-CoV 2. Also, these scaffolds show unique pharmacophores that can be utilized to design potential novel leads against SARS-CoV 2 for future treatment.