title: A Screen of FDA-Approved Drugs for Inhibitors of Zika Virus Infection.
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.
authors.affiliation: 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.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Barrows
authors.affiliation: 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.
authors.forename: Rafael K
authors.initials: RK
authors.lastname: Campos
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, 301 University Blvd, Galveston, TX 77555, USA.
authors.forename: Steven T
authors.initials: ST
authors.lastname: Powell
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, 301 University Blvd, Galveston, TX 77555, USA.
authors.forename: K Reddisiva
authors.initials: KR
authors.lastname: Prasanth
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, 301 University Blvd, Galveston, TX 77555, USA.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Schott-Lerner
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, 301 University Blvd, Galveston, TX 77555, USA.
authors.forename: Ruben
authors.initials: R
authors.lastname: Soto-Acosta
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, 301 University Blvd, Galveston, TX 77555, USA.
authors.forename: Gaddiel
authors.initials: G
authors.lastname: Galarza-Muñoz
authors.affiliation: Department of Neuroscience and Cell Biology, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555, USA.
authors.forename: Erica L
authors.initials: EL
authors.lastname: McGrath
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555, USA.
authors.forename: Rheanna
authors.initials: R
authors.lastname: Urrabaz-Garza
authors.affiliation: Department of Neuroscience and Cell Biology, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555, USA.
authors.forename: Junling
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Neuroscience and Cell Biology, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Wu
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555, USA.
authors.forename: Ramkumar
authors.initials: R
authors.lastname: Menon
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555, USA.
authors.forename: George
authors.initials: G
authors.lastname: Saade
authors.affiliation: Centro Regional de Investigación en Salud Publica INSP, 19 Poniente Esquina 4(a) Norte s/n, Colonia Centro, Tapachula, Chiapas 30700, C.P., Mexico.
authors.forename: Ildefonso
authors.initials: I
authors.lastname: Fernandez-Salas
authors.affiliation: 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.
authors.forename: Shannan L
authors.initials: SL
authors.lastname: Rossi
authors.affiliation: 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.
authors.forename: Nikos
authors.initials: N
authors.lastname: Vasilakis
authors.affiliation: 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.
authors.forename: Andrew
authors.initials: A
authors.lastname: Routh
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, 301 University Blvd, Galveston, TX 77555, USA. Electronic address: ssbradri@utmb.edu.
authors.forename: Shelton S
authors.initials: SS
authors.lastname: Bradrick
authors.affiliation: 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.
authors.forename: Mariano A
authors.initials: MA
authors.lastname: Garcia-Blanco
mesh_terms: D000998:Antiviral Agents / Q000302:isolation & purification* / Q000494:pharmacology*; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D058492:Drug Repositioning / Q000379:methods*; D006801:Humans; D000071244:Zika Virus / Q000187:drug effects* / Q000254:growth & development
chemical_list: D000998:Antiviral Agents