Barrows Nicholas J, Campos Rafael K, Powell Steven T, Prasanth K Reddisiva, Schott-Lerner Geraldine, Soto-Acosta Ruben, Galarza-Muñoz Gaddiel, McGrath Erica L, Urrabaz-Garza Rheanna, Gao Junling, Wu Ping, Menon Ramkumar, Saade George, Fernandez-Salas Ildefonso, Rossi Shannan L, Vasilakis Nikos, Routh Andrew, Bradrick Shelton S, Garcia-Blanco Mariano A
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, 301 University Blvd, Galveston, TX 77555, USA; Department of Molecular Genetics and Microbiology, Duke University, Durham, NC 27710, USA.
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, 301 University Blvd, Galveston, TX 77555, USA.
Cell Host Microbe. 2016 Aug 10;20(2):259-70. doi: 10.1016/j.chom.2016.07.004. Epub 2016 Jul 28.
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 antiviral 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.
目前尚无获批的疫苗或特定疗法来预防或治疗寨卡病毒(ZIKV)感染。我们研究了一个经美国食品药品监督管理局(FDA)批准的药物库,以了解它们阻断一种新分离的寨卡病毒毒株(ZIKV MEX_I_7)感染人HuH-7细胞的能力。在774种受试化合物中,有20多种在我们的体外筛选试验中降低了ZIKV感染。对选定的化合物进一步进行验证,以确定其对人宫颈、胎盘和神经干细胞系以及原代人羊膜细胞中ZIKV感染的抑制作用。已有的抗黄病毒药物(如硼替佐米和霉酚酸)以及其他以前未知具有抗病毒活性的药物(如达托霉素)被确定为ZIKV感染的抑制剂。几种药物在多种细胞类型中均降低了ZIKV感染。本研究确定了可在ZIKV感染临床研究中进行测试的药物,并提供了一个小分子资源库以研究ZIKV发病机制。