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结构病毒学:抗病毒治疗药物研发中的关键决定因素

Structural Virology: The Key Determinants in Development of Antiviral Therapeutics.

作者信息

Handa Tanuj, Saha Ankita, Narayanan Aarthi, Ronzier Elsa, Kumar Pravindra, Singla Jitin, Tomar Shailly

机构信息

Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Roorkee 247667, India.

Department of Biology, College of Science, George Mason University, Fairfax, VA 22030, USA.

出版信息

Viruses. 2025 Mar 14;17(3):417. doi: 10.3390/v17030417.

Abstract

Structural virology has emerged as the foundation for the development of effective antiviral therapeutics. It is pivotal in providing crucial insights into the three-dimensional frame of viruses and viral proteins at atomic-level or near-atomic-level resolution. Structure-based assessment of viral components, including capsids, envelope proteins, replication machinery, and host interaction interfaces, is instrumental in unraveling the multiplex mechanisms of viral infection, replication, and pathogenesis. The structural elucidation of viral enzymes, including proteases, polymerases, and integrases, has been essential in combating viruses like HIV-1 and HIV-2, SARS-CoV-2, and influenza. Techniques including X-ray crystallography, Nuclear Magnetic Resonance spectroscopy, Cryo-electron Microscopy, and Cryo-electron Tomography have revolutionized the field of virology and significantly aided in the discovery of antiviral therapeutics. The ubiquity of chronic viral infections, along with the emergence and reemergence of new viral threats necessitate the development of novel antiviral strategies and agents, while the extensive structural diversity of viruses and their high mutation rates further underscore the critical need for structural analysis of viral proteins to aid antiviral development. This review highlights the significance of structure-based investigations for bridging the gap between structure and function, thus facilitating the development of effective antiviral therapeutics, vaccines, and antibodies for tackling emerging viral threats.

摘要

结构病毒学已成为开发有效抗病毒疗法的基础。它对于在原子水平或近原子水平分辨率下深入了解病毒和病毒蛋白的三维结构至关重要。基于结构对病毒成分(包括衣壳、包膜蛋白、复制机制和宿主相互作用界面)进行评估,有助于揭示病毒感染、复制和发病机制的多种机制。对病毒酶(包括蛋白酶、聚合酶和整合酶)的结构解析,对于对抗HIV-1、HIV-2、SARS-CoV-2和流感等病毒至关重要。X射线晶体学、核磁共振光谱、冷冻电子显微镜和冷冻电子断层扫描等技术彻底改变了病毒学领域,并极大地助力了抗病毒疗法的发现。慢性病毒感染的普遍存在,以及新的病毒威胁的出现和再现,使得开发新型抗病毒策略和药物成为必要,而病毒广泛的结构多样性及其高突变率进一步凸显了对病毒蛋白进行结构分析以助力抗病毒研发的迫切需求。本综述强调了基于结构的研究对于弥合结构与功能之间差距的重要性,从而促进开发有效的抗病毒疗法、疫苗和抗体以应对新出现的病毒威胁。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dd2/11945554/542f7dfb5cc3/viruses-17-00417-g002.jpg

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