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对目前可用的抗呼吸道合胞病毒药物和研究性化合物的见解,重点关注其耐药性概况。

Insights into the Currently Available Drugs and Investigational Compounds Against RSV with a Focus on Their Drug-Resistance Profiles.

作者信息

Magnapera Alessia, Riccio Anna, Curcio Antonio, Tramontozzi Caterina, Piermatteo Lorenzo, D'Anna Stefano, Alcaro Stefano, Alteri Claudia, La Frazia Simone, Artese Anna, Salpini Romina, Svicher Valentina

机构信息

Department of Biology, University of Rome Tor Vergata, 00133 Rome, Italy.

Department of Health Science, Magna Graecia University, 88100 Catanzaro, Italy.

出版信息

Viruses. 2025 May 30;17(6):793. doi: 10.3390/v17060793.

DOI:10.3390/v17060793
PMID:40573384
Abstract

Respiratory syncytial virus (RSV) is a leading cause of severe respiratory illness in infants, young children, as well as elderly and immunocompromised patients worldwide. RSV is classified into two major subtypes, RSV-A and RSV-B, and remains the most frequently detected pathogen in infants hospitalized with acute respiratory infections. Recent advances have brought both passive and active immunization strategies, including FDA-approved vaccines for older adults and pregnant women and new monoclonal antibodies (mAbs) for infant protection. Although significant progress has been made, the need remains for improved antiviral treatments, particularly for vulnerable infants and immunocompromised patients. Recent studies have identified multiple RSV mutations that confer resistance to current treatments. These mutations, detected in both in vitro studies and clinical isolates, often complicate therapeutic outcomes, underscoring the need for updated and effective management strategies. In this context, evaluating protein flexibility through tools like DisoMine provides insight into how specific mutations impact structural dynamics at binding sites, thus affecting ligand affinity. This review aims to synthesize these aspects, offering a comprehensive insight into ongoing efforts to counteract RSV and address the evolving challenge of drug resistance.

摘要

呼吸道合胞病毒(RSV)是全球范围内导致婴儿、幼儿以及老年人和免疫功能低下患者发生严重呼吸道疾病的主要原因。RSV分为两种主要亚型,即RSV-A和RSV-B,并且仍然是因急性呼吸道感染住院的婴儿中最常检测到的病原体。最近的进展带来了被动和主动免疫策略,包括美国食品药品监督管理局(FDA)批准的针对老年人和孕妇的疫苗以及用于保护婴儿的新型单克隆抗体(mAb)。尽管已经取得了重大进展,但仍需要改进抗病毒治疗方法,特别是针对易受感染的婴儿和免疫功能低下的患者。最近的研究已经确定了多种对当前治疗产生耐药性的RSV突变。这些在体外研究和临床分离株中均检测到的突变,常常使治疗结果复杂化,凸显了对更新的有效管理策略的需求。在这种背景下,通过DisoMine等工具评估蛋白质灵活性,能够深入了解特定突变如何影响结合位点的结构动力学,从而影响配体亲和力。本综述旨在综合这些方面,全面深入地了解为对抗RSV以及应对不断演变的耐药性挑战所做的持续努力。

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本文引用的文献

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MARCH8 Restricts RSV Replication by Promoting Cellular Apoptosis Through Ubiquitin-Mediated Proteolysis of Viral SH Protein.MARCH8通过泛素介导的病毒SH蛋白蛋白水解促进细胞凋亡来限制呼吸道合胞病毒复制。
Viruses. 2024 Dec 18;16(12):1935. doi: 10.3390/v16121935.
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PubChem 2025 update.PubChem 2025更新版。
Nucleic Acids Res. 2025 Jan 6;53(D1):D1516-D1525. doi: 10.1093/nar/gkae1059.
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Mutating a flexible region of the RSV F protein can stabilize the prefusion conformation.突变 RSV F 蛋白的一个柔性区域可以稳定预融合构象。
Science. 2024 Sep 27;385(6716):1484-1491. doi: 10.1126/science.adp2362. Epub 2024 Sep 26.
4
Seasonality and severity of respiratory syncytial virus during the COVID-19 pandemic: a dynamic cohort study.在 COVID-19 大流行期间呼吸道合胞病毒的季节性和严重程度:一项动态队列研究。
Int J Infect Dis. 2024 Nov;148:107231. doi: 10.1016/j.ijid.2024.107231. Epub 2024 Sep 1.
5
A new mechanism of respiratory syncytial virus entry inhibition by small-molecule to overcome K394R-associated resistance.小分子通过一种新机制抑制呼吸道合胞病毒进入,克服 K394R 相关耐药性。
mBio. 2024 Sep 11;15(9):e0138524. doi: 10.1128/mbio.01385-24. Epub 2024 Aug 20.
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Direct-acting antivirals for RSV treatment, a review.直接作用抗病毒药物治疗 RSV,一篇综述。
Antiviral Res. 2024 Sep;229:105948. doi: 10.1016/j.antiviral.2024.105948. Epub 2024 Jul 5.
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Recent Progress toward the Discovery of Small Molecules as Novel Anti-Respiratory Syncytial Virus Agents.小分子作为新型抗呼吸道合胞病毒药物的最新研究进展。
J Med Chem. 2024 Jul 25;67(14):11543-11579. doi: 10.1021/acs.jmedchem.4c00630. Epub 2024 Jul 6.
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FDA approves mRNA-based RSV vaccine.美国食品药品监督管理局批准基于信使核糖核酸的呼吸道合胞病毒疫苗。
Nat Rev Drug Discov. 2024 Jul;23(7):487. doi: 10.1038/d41573-024-00095-3.
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Drugs Aging. 2024 Jun;41(6):487-505. doi: 10.1007/s40266-024-01118-9. Epub 2024 May 7.
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Author Correction: Molecular and phenotypic characteristics of RSV infections in infants during two nirsevimab randomized clinical trials.作者更正:两项尼塞韦单抗随机临床试验中婴儿呼吸道合胞病毒感染的分子和表型特征
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