Abstract

Prakriti Seth, Namrata Chatterjee, Ushashi Chakraborty and Prof. Dr. Nandan Kumar Jana*

ABSTRACT

Over the last 3 years, Coronavirus or COVID 19 has been a biological entity which led the entire world to a standstill. With over 630 million affected cases and 6.59 million deaths (recorded on 31stOctober 22), the world faced a dangerous pandemic situation and has foreseen millions of casualties in this period. Science and time came to rescue and vaccines were introduced in the market. Even though over time the fatal COVID-19 became a “flu-like” phenomenon its severity still remains unhindered. SARS-CoV-2 is still mutating every day and research is still going on in almost every nook and corner of the world to resist and more importantly, cure this disease. In this experiment, we performed in-silico drug-repurposing, i.e., virtually screening priorly approved drugs that can be also used for combating SARS-CoV-2. For this, we obtained the phylogenetic tree by comparing the whole genome sequence of SARS-CoV-2 with other closely-related viruses as noted in various scientific research. Following this, the target sequence of the main 3C-like protease (3CLpro) of SARS-CoV-2 extracted from PDB and similar template protein from the closest virus SARS-CoV were checked by homology modelling which yielded a 3-dimensional structure with 96% sequence identity. Virtual screening of the refined target with specified grid coordinates against diverse drug libraries revealed about 100 suitable, potential drug candidates. These drugs were then made to undergo molecular docking and those drugs with better binding energy and higher affinity to attach to the active sites were selected. These were then further shortlisted on the basis of site-specific individual docking scores and the number of active site attachments. Lastly, the top three drugs were filtered from the rest in accordance with appropriate ADMET profiles and carcinogenicity parameters. Evatanepag, Telcagepant and Tasosartan were found to be safe and non-toxic drugs capable of effectively interfering with the replication of the virus.