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

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.

Bioinformatics Analysis on Molecular Network and Bio-function ofBu-Fei-Yi- Shen Decoction / 世界科学技术-中医药现代化

This article was aimed to study the molecular network and bio-function ofBu-Fei-Yi-Shen (BFYS) decoction for chronic obstructive pulmonary disease (COPD) by bioinformatics analysis, in order to provide new ideas for research on pharmacological mechanism of Chinese medicine compound prescription. Components of herbs in BFYS decoction were searched in the databases. Targeted proteins of each component were found from PubChem. Comparison analyses were performed on molecular network, bio-function and canonical pathways by Ingenuity Pathway Analysis (IPA). The results showed that there were 239 target proteins of BFYS decoction. There were 9 molecular networks of BFYS decoction. The top 3 networks' functions were Cellular Development, Energy Production, and Cancer. The top 3 bio-function of BFYS decoction were Cellular Growth and Proliferation, Cell Death and Survival, and Inflammatory Response. The top 3 canonical pathways of BFYS decoction were Cell Cycle:G1/S Checkpoint Regulation, Chronic Myeloid Leukemia Signaling, and Cyclins and Cell Cycle Regulation. It was concluded that the search of target proteins for herbal compounds and bioinformatics analysis by IPA can be used to reveal the molecular network and bio-function of BFYS decoction.