A Screen of FDA-Approved Drugs for Inhibitors of Zika Virus Infection.
A Screen of FDA-Approved Drugs for Inhibitors of Zika Virus Infection.
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DOI：
10.1016/j.chom.2016.07.004
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发表时间：
2016-08-10
影响因子：
30.3
通讯作者：
Garcia-Blanco MA
中科院分区：
文献类型：
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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
目前还没有批准的疫苗或特定疗法来预防或治疗寨卡病毒（ZIKV）感染。我们询问了FDA批准的药物库，以了解其阻断新分离的ZIKV毒株（ZIKV MEX_I_7）感染人HuH-7细胞的能力。在我们的体外筛选测定中，774种测试化合物中超过20种降低ZIKV感染。进一步验证所选化合物在人宫颈、胎盘和神经干细胞系以及原代人羊膜细胞中抑制ZIKV感染。已建立的抗黄病毒药物（例如，硼替佐米和霉酚酸）和其它先前不具有已知抗病毒活性的药物（例如，达托霉素）被鉴定为ZIKV感染的抑制剂。几种药物减少了多种细胞类型的ZIKV感染。该研究鉴定了可以在ZIKV感染的临床研究中测试的药物，并提供了研究ZIKV发病机制的小分子资源。目前还没有批准的治疗寨卡病毒（ZIKV）感染的疗法。Barrows等人提出了FDA批准的药物在肝细胞瘤细胞系中的抗ZIKV活性的筛选。从20多个确定的候选化合物中选择的化合物在人神经干细胞和原代羊膜细胞中进行了验证。
Currently there are no approved vaccines or specific therapies to prevent or treat Zika virus (ZIKV) infection. We interrogated a library of FDA-approved drugs for their ability to block infection of human HuH-7 cells by a newly isolated ZIKV strain (ZIKV MEX_I_7). More than 20 out of 774 tested compounds decreased ZIKV infection in our in vitro screening assay. Selected compounds were further validated for inhibition of ZIKV infection in human cervical, placental and neural stem cell lines, as well as primary human amnion cells. Established anti-flaviviral drugs (e.g., bortezomib and mycophenolic acid) and others that had no previously known anti-viral activity (e.g., daptomycin) were identified as inhibitors of ZIKV infection. Several drugs reduced ZIKV infection across multiple cell types. This study identifies drugs that could be tested in clinical studies of ZIKV infection and provides a resource of small molecules to study ZIKV pathogenesis. Currently there is no approved therapy to treat Zika virus (ZIKV) infection. Barrows et al present a screen of FDA-approved drugs for anti-ZIKV activity in a hepatoma cell line. Selected compounds from the more than 20 identified candidates were validated in human neural stem cells and primary amnion cells.