Repurposing of HIV/HCV protease inhibitors against SARS-CoV-2 3CLpro.
Antiviral Res
; 207: 105419, 2022 11.
Article
in English
| MEDLINE | ID: covidwho-2041573
ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen that caused the global COVID-19 outbreak. The 3C-like protease (3CLpro) 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 3CLpro, 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 3CLpro 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 3CLpro in a dose-dependent manner. Among them, four compounds exhibited the ability to bind to 3CLproin vitro. HCV protease inhibitor simeprevir showed the most potency against 3CLpro with an EC50 vale of 2.6 µM, 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. Taken together, this work demonstrates the feasibility of using the cell-based BRET assay for screening 3CLpro inhibitors and supports the potential of simeprevir for the development of 3CLpro inhibitors.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
HIV Infections
/
Hepatitis C
/
HIV Protease Inhibitors
/
COVID-19 Drug Treatment
Type of study:
Prognostic study
Topics:
Variants
Limits:
Humans
Language:
English
Journal:
Antiviral Res
Year:
2022
Document Type:
Article
Affiliation country:
J.antiviral.2022.105419
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