Identification of a repurposed drug as an inhibitor of Spike protein of human coronavirus SARS-CoV-2 by computational methods

ABSTRACT

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) is an emerging new viral pathogen that causessevere respiratory disease. SARS-CoV-2 is responsible for the outbreak of COVID-19 pandemic worldwide.As there are no confirmed antiviral drugs or vaccines currently available for the treatment of COVID-19,discovering potent inhibitors or vaccines are urgently required for the benefit of humanity. The glycosylatedSpike protein (S-protein) directly interacts with human angiotensin-converting enzyme 2 (ACE2) receptorthrough the receptor-binding domain (RBD) of S-protein. As the S-protein is exposed to the surface and isessential for entry into the host, the S-protein can be considered as a first-line therapeutic target for antiviraltherapy and vaccine development. In silico screening, docking, and molecular dynamics simulation studieswere performed to identify repurposing drugs using DrugBank and PubChem library against the RBD ofS-protein. The study identified a laxative drug, Bisoxatin (DB09219), which is used for the treatment ofconstipation and preparation of the colon for surgical procedures. It binds nicely at the S-protein–ACE2interface by making substantial p-p interactions with Tyr505 in the ‘Site 1’ hook region of RBD andhydrophilic interactions with Glu406, Ser494, and Thr500. Bisoxatin consistently binds to the proteinthroughout the 100 ns simulation. Taken together, we propose that the discovered molecule, Bisoxatin may bea promising repurposable drug molecule to develop new chemical libraries for inhibiting SARS-CoV-2 entryinto the host.