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Drug Repurposing Approach Targeting Main Protease Using HTVS and Pharmacophoric Mapping: Exceptional Reassuring Itinerary for Most Insolvent Anti-SARS-CoV-2 Drug

Virupaksha A. Bastikar, Pramodkumar Gupta, Jaiprakash N. Sangshetti, Alpana V. Bastikar, Santosh S. Chhajed

Coronavirus pandemic COVID 19 has caused a wide range of harm worldwide with its inception in December 2019 in Wuhan, China. Till date there is no promising drug identified for the treatment of disease. In the view of this, scientists have elucidated X-ray structures of the proteins in SARS-CoV-2 virus. These can act as probable drug targets for the designing of drugs which is 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 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. Drug repurposing through in-silico docking analysis of existing FDA approved drugs was one method and high throughput screening of molecules from the ZINC database against main protease was the other technique applied. Two docking protocols were utilized- a fast docking algorithm to screen the hits or lead molecules followed by simulation based molecular dynamics docking procedure to optimize the obtained hits. 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 highest binding affinity. Unique molecules like lutein, beta carotene, Buprenorphine etc. were identified which can be used as repurposed drugs against SARS-CoV-2. Also these scaffolds show unique pharmacophores which can be utilized to design potential novel leads against SARS-CoV-2 for future treatment.