Virtual Screening of Inhibitors Against Spike Glycoprotein of 2019 Novel Corona Virus: a Drug Repurposing Approach
The novel coronavirus (2019-nCoV) is a human and animal pathogen recently emerged in the city of Wuhan in Hubei province of China, causing a spectrum of severe respiratory illnesses.Corona viruses makes entry in to human cells through its spike protein that binds to cell surface receptors. Wide spread of 2019-nCoV has been attributed to relatively high affinity of S protein to its receptor. Although highly important, unavailability of a high-resolution crystal structure and solvent accessible binding surface has made it a tedious target for current rapid virtual screening research groups. A homology model of the receptor binding domain (RBD) of 2019 -n CoV spike protein that is reasonably acceptable for drug screening was prepared using a high resolution crystal structure of SARS corona virus (SARS CoV) spike protein. Data obtained from RBD- receptor docking experiments and from molecular dynamics experiments were used to map a RBD- Receptor interaction hotspot that can be used to design small molecule inhibitors. The hot spot was then used for virtual screening of more than 3300 drugs approved by FDA and other authorities for clinical use. A cardiac glycoside (dgitoxin), two anthracyclines (zorubicin and aclarubicin), a tetracycline derivative (rolitetracycline), a cephalosporin (cefoperazone) and a food dye (E-155) were predicted to be most potent inhibitors of RBD – receptor interaction. An anti-asthmatic drug (zafirlukast) and several other drugs (itrazol, fazadinium, troglitazone, gliquidone, Idarubicin, Oxacillin) were found to be high affinity binders that may have a potential to inhibit RBD – receptor interaction. Results of present study suggest the potential of Zorubicin and its analogsas prophylactic medications or use in preventive measures.