Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods
By Canrong Wu, Yang Liu, Yueying Yang, Peng Zhang, Wu Zhong, Yali Wang, Qi-qi Wang, Yang Xu, Ming-xue Li, Xingzhou Li and 3 more. Acta Pharmaceutica Sinica B, 2020
2,011 citations recorded by the source corpus.
SARS-CoV-2 has caused tens of thousands of infections and more than one thousand deaths. There are currently no registered therapies for treating coronavirus infections. Because of time consuming process of new drug development, drug repositioning may be the only solution to the epidemic of sudden infectious diseases. We systematically analyzed all the proteins encoded by SARS-CoV-2 genes, compared them with proteins from other coronaviruses, predicted their structures, and built 19 structures that could be done by homology modeling. By performing target-based virtual ligand screening, a total of 21 targets (including two human targets) were screened against compound libraries including ZINC drug database and our own database of natural products. Structure and screening results of important targets such as 3-chymotrypsin-like protease (3CLpro), Spike, RNA-dependent RNA polymerase (RdRp), and papain like protease (PLpro) were discussed in detail. In addition, a database of 78 commonly used anti-viral drugs including those currently on the market and undergoing clinical trials for SARS-CoV-2 was constructed. Possible targets of these compounds and potential drugs acting on a certain target were predicted. This study will provide new lead compounds and targets for further in vitro and in vivo studies of SARS-CoV-2, new insights for those drugs currently ongoing clinical studies, and also possible new strategies for drug repositioning to treat SARS-CoV-2 infections.
Subfields: Computational Theory and Mathematics, Infectious Diseases, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/8cf9fa3a18e89f24ed670ce8a914504822b9aa0b
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In Computational Theory and Mathematics
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Citations in the corpus
- Structural basis for translational shutdown and immune evasion by the Nsp1 protein of SARS-CoV-2 (2020, background): “Due to its central role in weakening the anti-viral immune response, SARS-CoV Nsp1 has been proposed as a potential therapeutic target (19, 20).”
- Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): A molecular docking study (2020, background): “The results were promising and suggest possible inhibition from the currently available therapeutics against the newly emerged coronavirus [29].”
- SARS-CoV-2 (COVID-19) by the numbers (2020, background): “(Wu et al., 2020b): "SARS-CoV-2 genome has 10 open reading frames (Figure 2A)".”