Chloroquine, a FDA-approved Drug, Prevents Zika Virus Infection and its Associated Congenital Microcephaly in Mice.
Chloroquine, a FDA-approved Drug, Prevents Zika Virus Infection and its Associated Congenital Microcephaly in Mice.
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氯喹是 FDA 批准的药物，可预防寨卡病毒感染及其相关的小鼠先天性小头畸形
DOI：
10.1016/j.ebiom.2017.09.034
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发表时间：
2017-10
期刊：
影响因子：
11.1
通讯作者：
Cheng G
中科院分区：
文献类型：
--
作者：
Li C;Zhu X;Ji X;Quanquin N;Deng YQ;Tian M;Aliyari R;Zuo X;Yuan L;Afridi SK;Li XF;Jung JU;Nielsen-Saines K;Qin FX;Qin CF;Xu Z;Cheng G
寨卡病毒(Zika Virus，ZIKV)因其传播范围迅速扩大，并能导致小头畸形等严重先天性缺陷，已成为全球突发公共卫生事件。然而，目前还没有FDA批准的针对ZIKV感染的疗法或疫苗。通过我们对病毒进入抑制剂的筛选，我们发现氯喹(CQ)，一种常用的抗疟疾药物，也是FDA批准的药物，也被重新用于治疗其他病原体，通过阻止病毒内化，在体外可以显著抑制ZIKV感染。我们还证明了CQ可以降低ZIKV相关的小鼠发病率和死亡率。最后，我们证明了CQ对ZIKV感染引起的小鼠小头畸形有保护作用。事实证明，我们的方法是在筛查中关注先前识别的抗病毒药物对ZIKV的有效性，这是一种快速而有效的发现新的ZIKV疗法的方法。选择以前获得FDA批准的药物，如CQ，也可以提高它们更快进入临床测试和公众使用阶段的可能性。在测试的16种埃博拉病毒进入抑制剂中，有5种可以有效地抑制ZIKV的进入，氯喹可以在体外抑制ZIKV的内化，降低小鼠ZIKV相关的发病率和死亡率。氯喹预防ZIKV相关的小鼠先天性小头畸形。寨卡病毒(ZIKV)是一种新出现的病毒，可以导致出生缺陷，但目前还没有有效的治疗方法或疫苗。我们测试了16种已验证的埃博拉病毒细胞进入抑制剂对ZIKV感染的影响，发现氯喹(CQ)可以防止细胞培养中的ZIKV感染，这与先前的研究结果一致。然后，我们证明了CQ可以降低ZIKV相关小鼠的发病率和死亡率。最重要的是，它可以保护胎鼠免受ZIKV感染引起的小头畸形。因此，CQ是一种经临床试验有望用于治疗ZIKV感染的药物。
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. 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 mice Zika 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.
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DOI：
10.1056/nejmoa1602412
发表时间：
2016-12-15
期刊：
The New England journal of medicine
影响因子：
--
作者：
Brasil P;Pereira JP Jr;Moreira ME;Ribeiro Nogueira RM;Damasceno L;Wakimoto M;Rabello RS;Valderramos SG;Halai UA;Salles TS;Zin AA;Horovitz D;Daltro P;Boechat M;Raja Gabaglia C;Carvalho de Sequeira P;Pilotto JH;Medialdea-Carrera R;Cotrim da Cunha D;Abreu de Carvalho LM;Pone M;Machado Siqueira A;Calvet GA;Rodrigues Baião AE;Neves ES;Nassar de Carvalho PR;Hasue RH;Marschik PB;Einspieler C;Janzen C;Cherry JD;Bispo de Filippis AM;Nielsen-Saines K
通讯作者：
Nielsen-Saines K
影响因子：
64.5
作者：
Ma, Wenqiang;Li, Shihua;Gao, George Fu
通讯作者：
Gao, George Fu
影响因子：
4.9
作者：
Keyaerts, Els;Li, Sandra;Maes, Piet
通讯作者：
Maes, Piet
影响因子：
158.5
作者：
Driggers, R. W.;Ho, C. -Y.;Vapalahti, O.
通讯作者：
Vapalahti, O.
影响因子：
30.3
作者：
Barrows NJ;Campos RK;Powell ST;Prasanth KR;Schott-Lerner G;Soto-Acosta R;Galarza-Muñoz G;McGrath EL;Urrabaz-Garza R;Gao J;Wu P;Menon R;Saade G;Fernandez-Salas I;Rossi SL;Vasilakis N;Routh A;Bradrick SS;Garcia-Blanco MA
通讯作者：
Garcia-Blanco MA