In Silico Screening of Potential Spike Glycoprotein Inhibitors of SARS-CoV-2 with Drug Repurposing Strategy
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hinese Journal of Integrative Medicine
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Available online at link.springer.com/journal/11655 Journal homepage: www.cjim.cn/zxyjhen/zxyjhen/ch/index.aspx E-mail: [email protected]
Original Article
In Silico Screening of Potential Spike Glycoprotein Inhibitors of SARS-CoV-2 with Drug Repurposing Strategy WEI Tian-zi1,2,3, WANG Hao4,5, WU Xue-qing4,5, LU Yi2, GUAN Sheng-hui1, DONG Feng-quan5,6, DONG Chen-le7, ZHU Gu-li4,5, BAO Yu-zhou5,6, ZHANG Jian2, WANG Guan-yu1,8,9, and LI Hai-ying5,6 Objective: To select potential molecules that can target viral spike proteins, which may potentially ABSTRACT Objective: interrupt the interaction between the human angiotension-converting enzyme 2 (ACE2) receptor and viral spike protein Methods:: The three-dimensional (3D)-coordinate file of the receptor-binding domain (RBD)-ACE2 by virtual screening. Methods complex for searching a suitable docking pocket was firstly downloaded and prepared. Secondly, approximately 15,000 molecular candidates were prepared, including US Food and Drug Administration (FDA)-approved drugs from DrugBank and natural compounds from Traditional Chinese Medicine Systems Pharmacology (TCMSP), for the docking process. Then, virtual screening was performed and the binding energy in Autodock Vina was calculated. Finally, the top 20 molecules with high binding energy and their Chinese medicine (CM) herb sources were listed Results:: It was found that digitoxin, a cardiac glycoside in DrugBank and bisindigotin in TCMSP had in this paper. Results the highest docking scores. Interestingly, two of the CM herbs containing the natural compounds that had relatively high binding scores, Forsythiae fructus and Isatidis radix , are components of Lianhua Qingwen (莲花清瘟), a CM formula reportedly exerting activity against severe acute respiratory syndrome (SARS)-Cov-2. Moreover, raltegravir, Conclusions:: A class of compounds, an HIV integrase inhibitor, was found to have a relatively high binding score. Conclusions which are from FDA-approved drugs and CM natural compounds, that had high binding energy with RBD of the viral spike protein. Our work provides potential candidates for other researchers to identify inhibitors to prevent ©The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of SARS-CoV-2 infection, and highlights the importance Springer Nature 2020 of CM and integrative application of CM and Western Supported by National Natural Science Foundation of China medicine on treating COVID-19. (No. 61773196), Special Scientific Research Project on COVID-19 Epidemic Prevention and Control in Guangdong KEYWORDS COVID-19, SARS-CoV-2, drug Universities (No. 2020KZDZX1182), Guangdong Provincial Key repurposing, virtual screening, Chinese medicine Laboratory Funds (Nos. 2017B030301018, 2019B030301001), Since the middle of December 2019, a novel coronavirus disease (COVID-19) outbroke, and rapidly spread throughout the world, Early studies utilized realtime reverse transcription-polymerase chain reaction (RT-PCR
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