Lim Woo Young, Lee Ju Hyun, Choi Youngju, Yoon Keejung
Department of Biopharmaceutical Convergence, Sungkyunkwan University, Suwon, Gyeonggi-do 16419, South Korea.
Department of Microbiology, School of Medicine, Sungkyunkwan University, Suwon, Gyeonggi-do 16419, South Korea.
Virus Res. 2024 Dec;350:199475. doi: 10.1016/j.virusres.2024.199475. Epub 2024 Oct 8.
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.
人巨细胞病毒（HCMV）是一种来自β疱疹病毒亚科的双链DNA病毒，对新生儿和免疫功能低下的个体构成重大风险，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，识别出可抑制HCMV复制的FDA批准药物。使用HCMV子代检测法，发现维替泊芬（一种在光动力疗法中用作光敏剂的药物）以剂量依赖方式抑制HCMV产生，在低至0.5µM的浓度下显著降低复制，该浓度约为抗癌研究中所用浓度的1/20。进一步分析表明，维替泊芬不干扰HCMV进入宿主细胞或核转运，但在HCMV生命周期的即刻早期阶段就降低了病毒mRNA和蛋白质水平。这些结果表明，维替泊芬有潜力作为一种重新利用的药物被快速且安全地开发，以抑制HCMV感染。
