Identification of a repurposed drug as an inhibitor of Spike protein of human coronavirus SARS-CoV-2 by computational me
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J Biosci (2020)45:130 DOI: 10.1007/s12038-020-00102-w
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Identification of a repurposed drug as an inhibitor of Spike protein of human coronavirus SARS-CoV-2 by computational methods SRUTHI UNNI1, , SNEHAL AOUTI1, , SARAVANAMUTHU THIYAGARAJAN2 and BALASUNDARAM PADMANABHAN1* 1
Department of Biophysics, National Institute of Mental Health and Neuro Sciences (NIMHANS), Hosur Main Road, Bengaluru 560 029, India
2
Institute of Bioinformatics and Applied Biotechnology (IBAB), Biotech Park, Electronic City Phase I, Electronic City, Bengaluru 560 100, India *Corresponding author (Email, [email protected], [email protected])
These authors have contributed equally to this work.
MS received 3 May 2020; accepted 22 September 2020 Severe acute respiratory syndrome coronavirus (SARS-CoV-2) is an emerging new viral pathogen that causes severe 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 glycosylated Spike protein (S-protein) directly interacts with human angiotensin-converting enzyme 2 (ACE2) receptor through the receptor-binding domain (RBD) of S-protein. As the S-protein is exposed to the surface and is essential for entry into the host, the S-protein can be considered as a first-line therapeutic target for antiviral therapy and vaccine development. In silico screening, docking, and molecular dynamics simulation studies were performed to identify repurposing drugs using DrugBank and PubChem library against the RBD of S-protein. The study identified a laxative drug, Bisoxatin (DB09219), which is used for the treatment of constipation and preparation of the colon for surgical procedures. It binds nicely at the S-protein–ACE2 interface by making substantial p-p interactions with Tyr505 in the ‘Site 1’ hook region of RBD and hydrophilic interactions with Glu406, Ser494, and Thr500. Bisoxatin consistently binds to the protein throughout the 100 ns simulation. Taken together, we propose that the discovered molecule, Bisoxatin may be a promising repurposable drug molecule to develop new chemical libraries for inhibiting SARS-CoV-2 entry into the host. Keywords.
Bisoxatin; docking; DrugBank; MD simulations; PubChem; SARS-CoV-2; Spike protein
1. Introduction Severe acute respiratory syndrome coronavirus (SARSCoV) is a deadly pneumonia virus in humans (Drosten et al. 2003; Ksiazek et al. 2003). The term ‘‘coronavirus’’ is named from the ‘corona’-like or ‘crown’-like morphology observed for these viruses in the electronTopical Collection: Intervention.
COVID-19:
http://www.ias.ac.in/jbiosci
Disease
Biology
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microscopy images (Gui et al. 2017). SARS-CoV emerged in the Guangdong province of China in 2002 and spread to five continents through air travel routes, infecting about 8000 people and causing 774 deaths. Another deadly coronavirus
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