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 that recently emerged in the city of Wuhan in the Hubei province of China, causing a spectrum of severe respiratory illnesses. Coronaviruses make entry into human cells through its spike protein that binds to cell surface receptors. The wide spread of 2019-nCoV has been attributed to the relatively high affinity of S protein to its receptor. Although highly important, the 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 coronavirus (SARS CoV) spike protein.
Data obtained from RBD-receptor docking experiments and from molecular dynamics experiments were used to map an 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 the 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, and Oxacillin) were found to be high-affinity binders that may have a potential to inhibit RBD – receptor interaction. Results of the present study suggest the potential of Zorubicin and its analogues as prophylactic medications or use in preventive measures.
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