Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005; Suzhou Institute of Systems Medicine, Suzhou, Jiangsu 215123, China; Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
State Key Laboratory of Molecular Developmental Biology, CAS Center for Excellence in Brain Science and Intelligence Technology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
EBioMedicine. 2017 Oct;24:189-194. doi: 10.1016/j.ebiom.2017.09.034. Epub 2017 Sep 28.
Zika virus (ZIKV) has become a global public health emergency due to its rapidly expanding range and its ability to cause severe congenital defects such as microcephaly. However, there are no FDA-approved therapies or vaccines against ZIKV infection. Through our screening of viral entry inhibitors, we found that chloroquine (CQ), a commonly used antimalarial and a FDA-approved drug that has also been repurposed against other pathogens, could significantly inhibit ZIKV infection in vitro, by blocking virus internalization. We also demonstrated that CQ attenuates ZIKV-associated morbidity and mortality in mice. Finally, we proved that CQ protects fetal mice from microcephaly caused by ZIKV infection. Our methodology of focusing on previously identified antivirals in screens for effectiveness against ZIKV proved to be a rapid and efficient means of discovering new ZIKV therapeutics. Selecting drugs that were previously FDA-approved, such as CQ, also improves the likelihood that they may more quickly reach stages of clinical testing and use by the public.
寨卡病毒（ZIKV）因其迅速扩大的范围及其导致小头畸形等严重先天缺陷的能力而成为全球公共卫生紧急事件。然而，目前还没有针对 ZIKV 感染的 FDA 批准的治疗方法或疫苗。通过我们对病毒进入抑制剂的筛选，我们发现氯喹（CQ），一种常用的抗疟药物，也是一种已被重新用于对抗其他病原体的 FDA 批准药物，可通过阻断病毒内化来显著抑制 ZIKV 的体外感染。我们还证明 CQ 可减轻小鼠中寨卡病毒相关的发病率和死亡率。最后，我们证明 CQ 可保护胎儿免受寨卡病毒感染引起的小头畸形。我们专注于先前鉴定的抗病毒药物的筛选方法，以确定其对 ZIKV 的有效性，这被证明是发现新的 ZIKV 治疗方法的快速有效的手段。选择先前已获得 FDA 批准的药物，如 CQ，也增加了它们可能更快进入临床测试和公众使用阶段的可能性。
