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Basic Characteristics of Mutations
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Mutation Site
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P132H |
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Mutation Site Sentence
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HCV protease inhibitor simeprevir showed the most potency against 3CLpro with an EC50 vale of 2.6 muM, bound to the active site pocket of 3CLpro in a predicted model, and importantly, exhibited a similar activity against the protease containing the mutations P132H in Omicron variants. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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PLpro |
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Standardized Encoding Gene
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ORF1a
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Genotype/Subtype
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Omicron |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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Cell line
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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- |
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Location
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- |
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Literature Information
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PMID
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36155070
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Title
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Repurposing of HIV/HCV protease inhibitors against SARS-CoV-2 3CL(pro)
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Author
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Ma L,Li Q,Xie Y,Jianyuan Zhao,Yi D,Guo S,Guo F,Wang J,Yang L,Cen S
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Journal
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Antiviral research
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Journal Info
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2022 Nov;207:105419
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Abstract
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen that caused the global COVID-19 outbreak. The 3C-like protease (3CL(pro)) of SARS-CoV-2 plays a key role in virus replication and has become an ideal target for antiviral drug design. In this work, we have employed bioluminescence resonance energy transfer (BRET) technology to establish a cell-based assay for screening inhibitors against SARS-CoV-2 3CL(pro), and then applied the assay to screen a collection of known HIV/HCV protease inhibitors. Our results showed that the assay is capable of quantification of the cleavage efficiency of 3CL(pro) with good reproducibility (Z' factor is 0.59). Using the assay, we found that 9 of 26 protease inhibitors effectively inhibited the activity of SARS-CoV-2 3CL(pro) in a dose-dependent manner. Among them, four compounds exhibited the ability to bind to 3CL(pro)in vitro. HCV protease inhibitor simeprevir showed the most potency against 3CL(pro) with an EC(50) vale of 2.6 muM, bound to the active site pocket of 3CL(pro) in a predicted model, and importantly, exhibited a similar activity against the protease containing the mutations P132H in Omicron variants. Taken together, this work demonstrates the feasibility of using the cell-based BRET assay for screening 3CL(pro) inhibitors and supports the potential of simeprevir for the development of 3CL(pro) inhibitors.
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Sequence Data
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-
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