3-chymotrypsin-like protease in SARS-CoV-2.

IF 3.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Bioscience Reports Pub Date : 2024-08-28 DOI:10.1042/BSR20231395
Kenana Al Adem, Juliana C Ferreira, Adrian J Villanueva, Samar Fadl, Farah El-Sadaany, Imen Masmoudi, Yugmee Gidiya, Tariro Gurudza, Thyago H S Cardoso, Nitin K Saksena, Wael M Rabeh
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Abstract

Coronaviruses constitute a significant threat to the human population. Severe acute respiratory syndrome coronavirus-2, SARS-CoV-2, is a highly pathogenic human coronavirus that has caused the coronavirus disease 2019 (COVID-19) pandemic. It has led to a global viral outbreak with an exceptional spread and a high death toll, highlighting the need for effective antiviral strategies. 3-Chymotrypsin-like protease (3CLpro), the main protease in SARS-CoV-2, plays an indispensable role in the SARS-CoV-2 viral life cycle by cleaving the viral polyprotein to produce 11 individual non-structural proteins necessary for viral replication. 3CLpro is one of two proteases that function to produce new viral particles. It is a highly conserved cysteine protease with identical structural folds in all known human coronaviruses. Inhibitors binding with high affinity to 3CLpro will prevent the cleavage of viral polyproteins, thus impeding viral replication. Multiple strategies have been implemented to screen for inhibitors against 3CLpro, including peptide-like and small molecule inhibitors that covalently and non-covalently bind the active site, respectively. In addition, allosteric sites of 3CLpro have been identified to screen for small molecules that could make non-competitive inhibitors of 3CLpro. In essence, this review serves as a comprehensive guide to understanding the structural intricacies and functional dynamics of 3CLpro, emphasizing key findings that elucidate its role as the main protease of SARS-CoV-2. Notably, the review is a critical resource in recognizing the advancements in identifying and developing 3CLpro inhibitors as effective antiviral strategies against COVID-19, some of which are already approved for clinical use in COVID-19 patients.

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SARS-CoV-2 中的 3C 类蛋白酶。
冠状病毒对人类构成重大威胁。严重急性呼吸系统综合征冠状病毒-2(SARS-CoV-2)是一种高致病性人类冠状病毒,曾引发 COVID-19 大流行。它导致全球病毒爆发,传播速度极快,死亡人数众多,突出表明需要有效的抗病毒策略。3-糜蛋白酶样蛋白酶(3CLpro)是 SARS-CoV-2 的主要蛋白酶,在 SARS-CoV-2 病毒生命周期中发挥着不可或缺的作用,它能裂解病毒多聚蛋白,产生病毒复制所需的 11 种独立的非结构蛋白。3CLpro 是产生新病毒颗粒的两种蛋白酶之一。它是一种高度保守的半胱氨酸蛋白酶,在所有已知的人类冠状病毒中都具有相同的结构褶皱。与 3CLpro 高亲和力结合的抑制剂将阻止病毒多聚蛋白的裂解,从而阻碍病毒复制。筛选 3CLpro 抑制剂的方法有多种,包括分别与活性位点共价结合和非共价结合的类肽抑制剂和小分子抑制剂。此外,还确定了 3CLpro 的异构位点,以筛选可成为 3CLpro 非竞争性抑制剂的小分子。从本质上讲,这篇综述是了解 3CLpro 复杂结构和功能动态的全面指南,强调了阐明其作为 SARS-CoV-2 主要蛋白酶作用的关键发现。值得注意的是,这篇综述是认识 3CLpro 抑制剂作为针对 COVID-19 的有效抗病毒策略的鉴定和开发进展的重要资源,其中一些抑制剂已被批准用于 COVID-19 患者的临床治疗。
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来源期刊
Bioscience Reports
Bioscience Reports 生物-细胞生物学
CiteScore
8.50
自引率
0.00%
发文量
380
审稿时长
6-12 weeks
期刊介绍: Bioscience Reports provides a home for sound scientific research in all areas of cell biology and molecular life sciences. Since 2012, Bioscience Reports has been fully Open Access and publishes all papers under the liberal CC BY licence, giving the life science community quality research to share and discuss.Content before 2012 is subscription-only, and is accessible via archive purchase. Articles are assessed on soundness, providing a home for valid findings and data. We welcome papers that span disciplines (e.g. chemistry, medicine), including papers describing: -new methodologies -tools and reagents to probe biological questions -mechanistic details -disease mechanisms -metabolic processes and their regulation -structure and function -bioenergetics
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