Development of a Fluorescence Polarization Assay for the SARS-CoV-2 Papain-like Protease.

IF 4.9 Q1 CHEMISTRY, MEDICINAL
ACS Pharmacology and Translational Science Pub Date : 2025-02-26 eCollection Date: 2025-03-14 DOI:10.1021/acsptsci.4c00642
Kan Li, Prakash Jadhav, Yu Wen, Haozhou Tan, Jun Wang
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引用次数: 0

Abstract

The COVID-19 pandemic has caused significant losses to the global community. Although effective vaccination and antiviral therapeutics provide primary defense, SARS-CoV-2 remains a public health threat, given the emerging resistant variants. The SARS-CoV-2 papain-like protease (PLpro) is essential for viral replication and is a promising drug target. We recently designed a series of biarylphenyl PLpro inhibitors with a representative lead Jun12682 showing potent antiviral efficacy in a SARS-CoV-2 infection mouse model. In this study, we designed a fluorescein-labeled biarylphenyl probe Jun12781 and used it to optimize a fluorescence polarization (FP) assay. The FP assay is suitable for high-throughput screening with a Z' factor of 0.69. In addition, we found a positive correlation between the FP binding affinity and the enzymatic inhibitory potency of PLpro inhibitors, suggesting that the FP assay is valid in characterizing the binding affinity of PLpro inhibitors.

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来源期刊
ACS Pharmacology and Translational Science
ACS Pharmacology and Translational Science Medicine-Pharmacology (medical)
CiteScore
10.00
自引率
3.30%
发文量
133
期刊介绍: ACS Pharmacology & Translational Science publishes high quality, innovative, and impactful research across the broad spectrum of biological sciences, covering basic and molecular sciences through to translational preclinical studies. Clinical studies that address novel mechanisms of action, and methodological papers that provide innovation, and advance translation, will also be considered. We give priority to studies that fully integrate basic pharmacological and/or biochemical findings into physiological processes that have translational potential in a broad range of biomedical disciplines. Therefore, studies that employ a complementary blend of in vitro and in vivo systems are of particular interest to the journal. Nonetheless, all innovative and impactful research that has an articulated translational relevance will be considered. ACS Pharmacology & Translational Science does not publish research on biological extracts that have unknown concentration or unknown chemical composition. Authors are encouraged to use the pre-submission inquiry mechanism to ensure relevance and appropriateness of research.
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