Verteporfin 是一种有效的 HCMV 复制抑制剂。

IF 2.5 4区 医学 Q3 VIROLOGY Virus research Pub Date : 2024-10-08 DOI:10.1016/j.virusres.2024.199475
Woo Young Lim , Ju Hyun Lee , Youngju Choi , Keejung Yoon
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引用次数: 0

摘要

人类巨细胞病毒(HCMV)是一种 Betaherpesvirinae 亚科的双链 DNA 病毒,对新生儿和免疫力低下的人构成重大风险,可能导致严重的神经发育障碍。本研究的目的是通过药物重新定位方法,找出可抑制 HCMV 复制的 FDA 批准药物。通过 HCMV 原代检测发现,在光动力疗法中用作光敏剂的药物 verteporfin 能以剂量依赖的方式抑制 HCMV 的产生,在低至 0.5 µM(约为抗癌研究所用浓度的 1/20)的浓度下就能显著减少复制。进一步的分析表明,verteporfin 不会干扰 HCMV 宿主细胞的进入或核转运,但会降低 HCMV 生命周期中从早期阶段开始的病毒 mRNA 和蛋白质水平。这些结果表明,verteporfin 有可能被快速、安全地开发为抑制 HCMV 感染的再利用药物。
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Verteporfin is an effective inhibitor of HCMV replication
Human cytomegalovirus (HCMV), a double-stranded DNA virus from the Betaherpesvirinae subfamily, constitutes significant risks to newborns and immunocompromised individuals, potentially leading to severe neurodevelopmental disorders. The purpose of this study was to identify FDA-approved drugs that can inhibit HCMV replication through a drug repositioning approach. Using an HCMV progeny assay, verteporfin, a medication used as a photosensitizer in photodynamic therapy, was found to inhibit HCMV production in a dose-dependent manner, significantly reducing replication at concentrations as low as 0.5 µM, approximately 1/20th of the concentration used in anti-cancer research. Further analysis revealed that verteporfin did not interfere with HCMV host cell entry or nuclear transport but reduced viral mRNA and protein levels throughout the HCMV life cycle from the immediate-early stages. These results suggest that verteporfin has the potential to be rapidly and safely developed as a repurposed drug to inhibit HCMV infection.
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来源期刊
Virus research
Virus research 医学-病毒学
CiteScore
9.50
自引率
2.00%
发文量
239
审稿时长
43 days
期刊介绍: Virus Research provides a means of fast publication for original papers on fundamental research in virology. Contributions on new developments concerning virus structure, replication, pathogenesis and evolution are encouraged. These include reports describing virus morphology, the function and antigenic analysis of virus structural components, virus genome structure and expression, analysis on virus replication processes, virus evolution in connection with antiviral interventions, effects of viruses on their host cells, particularly on the immune system, and the pathogenesis of virus infections, including oncogene activation and transduction.
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