Portal de Periódicos da CAPES

Chloroquine, a FDA-approved Drug, Prevents Zika Virus Infection and its Associated Congenital Microcephaly in Mice

2017; Elsevier BV; Volume: 24; Linguagem: Inglês

10.1016/j.ebiom.2017.09.034

2352-3964

Chunfeng Li, Xingliang Zhu, Xue Ji, Natalie Quanquin, Yong-Qiang Deng, Min Tian, Roghiyh Aliyari, Xiangyang Zuo, Ling Yuan, Shabbir Khan Afridi, Xiaofeng Li, Jae U. Jung, Karin Nielsen‐Saines, F. Xiao‐Feng Qin, Cheng‐Feng Qin, Zhiheng Xu, Genhong Cheng,

Viral Infections and Vectors

Highlights•5 out 16 tested Ebola virus entry inhibitors can inhibit ZIKV entry efficiently•Chloroquine can inhibit ZIKV internalization in vitro and reduce ZIKV-associated morbidity and mortality in mice•Chloroquine prevents ZIKV-associated congenital microcephaly in miceZika virus (ZIKV) is an emerging virus which can cause birth defects, however there are currently no effective treatments or vaccines. We tested the effects of 16 verified Ebola virus cell entry inhibitors on ZIKV infection, and found that chloroquine (CQ) could prevent ZIKV infection in cell cultures, consistent with results from a previous study. We then demonstrated that CQ can reduce ZIKV-associated morbidity and mortality in mice. Most importantly, it protects fetal mice from microcephaly caused by ZIKV infection. Therefore, CQ is a potential drug which would be used to treat ZIKV infection after clinical test.AbstractZika 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.