基础研究 情报发生 2026-10-31 · 发布于 2026-11-01

司帕沙星揭示抗呼吸道合胞病毒的双靶点骨架:同时作用于宿主与病毒

来源:Commun Biol · PMID 42963363 · DOI 10.1038/s42003-026-10744-5 · 来源:IMA 知识库《文献层·文献监控卡片》2026-10-31 期 · 全文级(file_id dmlmcfQeUyzO,实际下载核验) · 全文已获取并通过归属校验

时间标签:数据日期 2026-10-31 · 生成时间 2026-11-01 05:30(Asia/Shanghai)| 检索窗口 PubMed edat 2026/10/28–2026/10/31 | 情报发生日期 2026-10-31

研究问题

However, these drugs show limited efficacy once infection has progressed to the lower respiratory tract5, while the clinical use of ribavirin is constrained by toxicity, high cost, and low specificity for RSV6, 7.;While direct-acting antivirals (DAAs) targeting structural proteins face challenges posed by escape mutants, targeting the viral replication machinery, along with essential host cofactors remains a relatively underutilized strategy for achieving durable clinical efficacy.;However, host-directed antiviral strategies raise legitimate concerns regarding safety and off- target effects, particularly in vulnerable populations such as young children.

方法

Here, we performed a clinically guided, medium-throughput screening of approved drugs used in pediatric populations and identified sparfloxacin (SPFX), a fluoroquinolone antibiotic, as a mechanistically informative antiviral scaffold.;Currently, approved options include the anti-F monoclonal antibody palivizumab and the broad-spectrum antiviral ribavirin.;Thus, we aimed to streamline anti-RSV drug discovery by integrating primary pediatric airway epithelial models with clinically guided screening of approved drugs, leading to the identification of sparfloxacin (SPFX), a fluoroquinolone antibiotic, as an antiviral scaffold that suppresses RSV replication in vitro and in vivo.;Subsequently, given the availability of structurally related fluoroquinolones (Supplementary Fig. 2A), we evaluated the anti-RSV activity of fluoroquinolones (Fig. 1D and Supplementary Fig. 2B).

核心结论

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.;The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material.;If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. ‖ 结论:Together, these findings support a host– A R T I C L E I N P R E S S ARTICLE IN PRESS virus dual-target framework for RSV therapeutic development and provide a mechanistic foundation for future optimization of quinolone-derived antiviral compounds.

局限

Collectively, these limitations underscore the urgent need for new antiviral approaches with improved efficacy and durability.;These limitations highlight the need for clinically tractable antiviral scaffolds with improved durability and mechanistic versatility.;We hypothesized that clinically used drugs could serve as a source of lead compounds capable of simultaneously modulating viral replication and host cellular pathways, thereby overcoming key limitations of virus-centric antiviral strategies, including resistance and limited durability.

对本项目的价值

★☆☆☆☆ 相关范围内,作为背景与横向对照收录。

全文来源

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原文题录

  • 英文标题:Sparfloxacin reveals a host-virus dual-target antiviral scaffold against respiratory syncytial virus.
  • 期刊与标识:Commun Biol · PMID 42963363 · DOI 10.1038/s42003-026-10744-5

B 级证据分级:B 级(同行评议临床前研究,主要为动物模型)

本文核心结论来自动物模型或体外细胞学,属临床前证据,不能外推至人体。「延长健康寿命」「改善功能」等表述在小鼠中的意义,与人类临床结局之间仍有距离。

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