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

Nicholas J Barrows; Rafael K Campos; Steven T Powell; K Reddisiva Prasanth; Geraldine Schott-Lerner; Ruben Soto-Acosta; Gaddiel Galarza-Muñoz; Erica L McGrath; Rheanna Urrabaz-Garza; Junling Gao; Ping Wu; Ramkumar Menon; George Saade; Ildefonso Fernandez-Salas; Shannan L Rossi; Nikos Vasilakis; Andrew Routh; Shelton S Bradrick; Mariano A Garcia-Blanco

doi:10.1016/j.chom.2016.07.004

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

Cell Host Microbe. 2016 Aug 10;20(2):259-70. doi: 10.1016/j.chom.2016.07.004. Epub 2016 Jul 28.

Authors

Nicholas J Barrows¹, Rafael K Campos¹, Steven T Powell², K Reddisiva Prasanth², Geraldine Schott-Lerner², Ruben Soto-Acosta², Gaddiel Galarza-Muñoz², Erica L McGrath³, Rheanna Urrabaz-Garza⁴, Junling Gao³, Ping Wu³, Ramkumar Menon⁴, George Saade⁴, Ildefonso Fernandez-Salas⁵, Shannan L Rossi⁶, Nikos Vasilakis⁶, Andrew Routh⁷, Shelton S Bradrick⁸, Mariano A Garcia-Blanco⁹

Affiliations

¹ 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.
² Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, 301 University Blvd, Galveston, TX 77555, USA.
³ Department of Neuroscience and Cell Biology, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555, USA.
⁴ Department of Obstetrics and Gynecology, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555, USA.
⁵ Centro Regional de Investigación en Salud Publica INSP, 19 Poniente Esquina 4(a) Norte s/n, Colonia Centro, Tapachula, Chiapas 30700, C.P., Mexico.
⁶ Department of Pathology, Center for Biodefense and Emerging Infectious Diseases, Center for Tropical Diseases, and Institute for Human Infections and Immunity, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555, USA.
⁷ Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, 301 University Blvd, Galveston, TX 77555, USA; Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555, USA.
⁸ Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, 301 University Blvd, Galveston, TX 77555, USA. Electronic address: ssbradri@utmb.edu.
⁹ Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, 301 University Blvd, Galveston, TX 77555, USA; Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore 169857, Republic of Singapore. Electronic address: maragarc@utmb.edu.

Abstract

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.

MeSH terms

Antiviral Agents / isolation & purification*
Antiviral Agents / pharmacology*
Cells, Cultured
Drug Evaluation, Preclinical / methods*
Drug Repositioning / methods*
Humans
Zika Virus / drug effects*
Zika Virus / growth & development

Substances

Antiviral Agents

Abstract

MeSH terms

Substances

Grants and funding