一种评估NCp7 RNA结合活性的高通量方法用于HIV-1药物发现。

IF 2.7 4区生物学 Q2 BIOCHEMICAL RESEARCH METHODS

SLAS Discovery Pub Date : 2025-08-11 DOI:10.1016/j.slasd.2025.100260

Joanna K. Winstone , Rikki Uhrich , Thibault Alle , Brian C. Kraemer

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引用次数: 0

摘要

HIV-1流行病广泛影响医疗保健。仍然需要继续改进抗病毒疗法，以适应耐药性的发展。HIV-1核衣壳蛋白7 （NCp7）似乎是一个主要的药物靶点，因为它独特的核酸伴侣活性需要多个病毒过程。NCp7 RNA结合活性已被证明可以增加病毒在宿主体内的产生和传染性。在这里，我们引入了一种高通量的AlphaScreen方法来评估NCp7 RNA结合活性，并使用已知的抑制剂验证其特异性和敏感性。我们还通过进行药物再利用筛选证明了该分析的实用性，该筛选确定了7种确认的NCp7 RNA结合抑制剂和2种确认的NCp7 RNA结合增强剂。该工具将有助于未来针对ncp7的药物发现计划，用于治疗HIV-1感染。

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A high-throughput approach to evaluating NCp7 RNA binding activity for HIV-1 drug discovery

The HIV-1 epidemic broadly impacts healthcare. There remains a continued need for improved anti-viral therapies resilient to the development of drug resistance. HIV-1 nucleocapsid protein 7 (NCp7) seems a prime drug target due to its unique nucleic acid chaperone activity required for multiple viral processes. NCp7 RNA binding activity has been shown to increase viral production and infectivity within the host. Here we introduce a high-throughput AlphaScreen assay to evaluate NCp7 RNA binding activity and validate its specificity and sensitivity using a known inhibitor. We also demonstrate the utility of this assay by performing a drug-repurposing screen, which identified seven confirmed inhibitors of NCp7 RNA binding and two confirmed enhancers of NCp7 RNA binding. This tool will aid in future NCp7-targeted drug discovery initiatives for the treatment of HIV-1 infection.

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来源期刊

SLAS Discovery Chemistry-Analytical Chemistry

CiteScore

7.00

自引率

3.20%

发文量

审稿时长

39 days

期刊介绍： Advancing Life Sciences R&D: SLAS Discovery reports how scientists develop and utilize novel technologies and/or approaches to provide and characterize chemical and biological tools to understand and treat human disease. SLAS Discovery is a peer-reviewed journal that publishes scientific reports that enable and improve target validation, evaluate current drug discovery technologies, provide novel research tools, and incorporate research approaches that enhance depth of knowledge and drug discovery success. SLAS Discovery emphasizes scientific and technical advances in target identification/validation (including chemical probes, RNA silencing, gene editing technologies); biomarker discovery; assay development; virtual, medium- or high-throughput screening (biochemical and biological, biophysical, phenotypic, toxicological, ADME); lead generation/optimization; chemical biology; and informatics (data analysis, image analysis, statistics, bio- and chemo-informatics). Review articles on target biology, new paradigms in drug discovery and advances in drug discovery technologies. SLAS Discovery is of particular interest to those involved in analytical chemistry, applied microbiology, automation, biochemistry, bioengineering, biomedical optics, biotechnology, bioinformatics, cell biology, DNA science and technology, genetics, information technology, medicinal chemistry, molecular biology, natural products chemistry, organic chemistry, pharmacology, spectroscopy, and toxicology. SLAS Discovery is a member of the Committee on Publication Ethics (COPE) and was published previously (1996-2016) as the Journal of Biomolecular Screening (JBS).