Human respiratory syncytial virus (hRSV) is a major cause of respiratory illness in young children and can cause severe infections in the elderly or in immunocompromised adults. To date, there is no vaccine to prevent hRSV infections, and disease management is limited to preventive care by palivizumab in infants and supportive care for adults. Intervention with small-molecule antivirals specific for hRSV represents a good alternative, but no such compounds are currently approved. The investigation of existing drugs for new therapeutic purposes (drug repositioning) can be a faster approach to address this issue. In this study, we show that chloroquine and pyrimethamine inhibit the replication of human respiratory syncytial virus A (long strain) and synergistically increase the anti-replicative effect of ribavirin in cellulo. Moreover, chloroquine, but not pyrimethamine, inhibits hRSV replication in the mouse model. Our results show that chloroquine can potentially be an interesting compound for treatment of hRSV infection in monotherapy or in combination with other antivirals.

中文翻译：

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氯喹和乙胺嘧啶抑制人呼吸道合胞病毒A的复制

人类呼吸道合胞病毒 (hRSV) 是幼儿呼吸道疾病的主要原因，可导致老年人或免疫功能低下的成年人严重感染。迄今为止，尚无预防 hRSV 感染的疫苗，疾病管理仅限于婴儿的帕利珠单抗预防性护理和成人的支持性护理。对 hRSV 特异的小分子抗病毒药物进行干预是一种很好的替代方法，但目前尚无此类化合物获得批准。为新的治疗目的（药物重新定位）研究现有药物可能是解决这个问题的更快方法。在本研究中，我们表明氯喹和乙胺嘧啶可抑制人呼吸道合胞病毒 A（长株）的复制，并协同增加利巴韦林在纤维素中的抗复制作用。. 此外，氯喹（而非乙胺嘧啶）可抑制小鼠模型中的 hRSV 复制。我们的结果表明，氯喹可能是一种有趣的化合物，可用于单一疗法或与其他抗病毒药物联合治疗 hRSV 感染。