Structural review of SARS-CoV-2 antiviral targets

IF 4.4 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Structure Pub Date : 2024-09-05 DOI:10.1016/j.str.2024.08.005

Wen Cui, Yinkai Duan, Yan Gao, Wei Wang, Haitao Yang

引用次数: 0

Abstract

The coronavirus disease 2019 (COVID-19), the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), represents the most disastrous infectious disease pandemic of the past century. As a member of the Betacoronavirus genus, the SARS-CoV-2 genome encodes a total of 29 proteins. The spike protein, RNA-dependent RNA polymerase, and proteases play crucial roles in the virus replication process and are promising targets for drug development. In recent years, structural studies of these viral proteins and of their complexes with antibodies and inhibitors have provided valuable insights into their functions and laid a solid foundation for drug development. In this review, we summarize the structural features of these proteins and discuss recent progress in research regarding therapeutic development, highlighting mechanistically representative molecules and those that have already been approved or are under clinical investigation.

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SARS-CoV-2 抗病毒靶标的结构回顾

冠状病毒病 2019（COVID-19）是由严重急性呼吸系统综合征冠状病毒 2（SARS-CoV-2）引起的疾病，是上个世纪最具灾难性的传染病大流行。作为 Betacoronavirus 属的一员，SARS-CoV-2 基因组共编码 29 种蛋白质。尖峰蛋白、RNA 依赖性 RNA 聚合酶和蛋白酶在病毒复制过程中起着至关重要的作用，是很有希望的药物开发目标。近年来，对这些病毒蛋白及其与抗体和抑制剂复合物的结构研究为了解其功能提供了宝贵的信息，为药物开发奠定了坚实的基础。在这篇综述中，我们总结了这些蛋白质的结构特征，并讨论了有关治疗开发的最新研究进展，重点介绍了在机理上具有代表性的分子以及那些已经获得批准或正在进行临床研究的分子。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Structure 生物-生化与分子生物学

CiteScore

8.90

自引率

1.80%

发文量

155

审稿时长

3-8 weeks

期刊介绍： Structure aims to publish papers of exceptional interest in the field of structural biology. The journal strives to be essential reading for structural biologists, as well as biologists and biochemists that are interested in macromolecular structure and function. Structure strongly encourages the submission of manuscripts that present structural and molecular insights into biological function and mechanism. Other reports that address fundamental questions in structural biology, such as structure-based examinations of protein evolution, folding, and/or design, will also be considered. We will consider the application of any method, experimental or computational, at high or low resolution, to conduct structural investigations, as long as the method is appropriate for the biological, functional, and mechanistic question(s) being addressed. Likewise, reports describing single-molecule analysis of biological mechanisms are welcome. In general, the editors encourage submission of experimental structural studies that are enriched by an analysis of structure-activity relationships and will not consider studies that solely report structural information unless the structure or analysis is of exceptional and broad interest. Studies reporting only homology models, de novo models, or molecular dynamics simulations are also discouraged unless the models are informed by or validated by novel experimental data; rationalization of a large body of existing experimental evidence and making testable predictions based on a model or simulation is often not considered sufficient.

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