A Screen of FDA-Approved Drugs for Inhibitors of Zika Virus Infection

被引：386

作者：

Barrows, Nicholas J. ^{[1
,2
]}

Campos, Rafael K. ^{[1
,2
]}

Powell, Steven T. ^{[1
]}

Prasanth, K. Reddisiva ^{[1
]}

Schott-Lerner, Geraldine ^{[1
]}

Soto-Acosta, Ruben ^{[1
]}

Galarza-Munoz, Gaddiel ^{[1
]}

McGrath, Erica L. ^{[3
]}

Urrabaz-Garza, Rheanna ^{[4
]}

Gao, Junling ^{[3
]}

Wu, Ping ^{[3
]}

Menon, Ramkumar ^{[4
]}

Saade, George ^{[4
]}

Fernandez-Salas, Ildefonso ^{[5
]}

Rossi, Shannan L. ^{[6
,7
]}

Vasilakis, Nikos ^{[6
,7
]}

Routh, Andrew ^{[1
,8
]}

Bradrick, Shelton S. ^{[1
]}

Garcia-Blanco, Mariano A. ^{[1
,9
]}

机构：

[1] Univ Texas Med Branch, Dept Biochem & Mol Biol, 301 Univ Blvd, Galveston, TX 77555 USA

[2] Duke Univ, Dept Mol Genet & Microbiol, Durham, NC 27710 USA

[3] Univ Texas Med Branch, Dept Neurosci & Cell Biol, 301 Univ Blvd, Galveston, TX 77555 USA

[4] Univ Texas Med Branch, Dept Obstet & Gynecol, 301 Univ Blvd, Galveston, TX 77555 USA

[5] Ctr Reg Invest Salud Publ INSP, 19 Poniente Esquina 4a Norte S-N, Tapachula 30700, Chiapas, Mexico

[6] Univ Texas Med Branch, Ctr Biodef & Emerging Infect Dis, Ctr Trop Dis, Dept Pathol, 301 Univ Blvd, Galveston, TX 77555 USA

[7] Univ Texas Med Branch, Inst Human Infect & Immun, 301 Univ Blvd, Galveston, TX 77555 USA

[8] Univ Texas Med Branch, Sealy Ctr Struct Biol & Mol Biophys, 301 Univ Blvd, Galveston, TX 77555 USA

[9] Duke NUS Med Sch, Programme Emerging Infect Dis, Singapore 169857, Singapore

来源：

CELL HOST & MICROBE | 2016年 / 20卷 / 02期

关键词：

CLINICAL PHARMACOKINETICS; FLAVIVIRUS REPLICATION; MYCOPHENOLIC-ACID; NUCLEAR IMPORT; LONG-TERM; DENGUE; IVERMECTIN; DISCOVERY; CELLS; TOLERABILITY;

D O I：

10.1016/j.chom.2016.07.004

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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.

引用

页码：259 / 270

页数：12

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