Inhibitors of cellular kinases with broad-spectrum antiviral activity for hemorrhagic fever viruses

  • Antiviral Res. 2015 Aug:120:40-7. doi: 10.1016/j.antiviral.2015.05.003.
Emma L Mohr  1 ,  Laura K McMullan  2 ,  Michael K Lo  2 ,  Jessica R Spengler  2 ,  Éric Bergeron  2 ,  César G Albariño  2 ,  Punya Shrivastava-Ranjan  2 ,  Cheng-Feng Chiang  2 ,  Stuart T Nichol  2 ,  Christina F Spiropoulou  3 ,  Mike Flint  2
Affiliations
  • 1. Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, MS G-14, Atlanta, GA 30333, USA; Emory University Department of Pediatrics, Emory-Children's Center, 2015 Uppergate Drive, Atlanta, GA 30322, USA.
  • 2. Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, MS G-14, Atlanta, GA 30333, USA.
  • 3. Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, MS G-14, Atlanta, GA 30333, USA. Electronic address: [email protected].
PMID: 25986249 DOI: 10.1016/j.antiviral.2015.05.003
Abstract

Host cell kinases are important for the replication of a number of hemorrhagic fever viruses. We tested a panel of kinase inhibitors for their ability to block the replication of multiple hemorrhagic fever viruses. OSU-03012 inhibited the replication of Lassa, Ebola, Marburg and Nipah viruses, whereas BIBX 1382 dihydrochloride inhibited Lassa, Ebola and Marburg viruses. BIBX 1382 blocked both Lassa and Ebola virus glycoprotein-dependent cell entry. These compounds may be used as tools to understand conserved virus-host interactions, and implicate host cell kinases that may be targets for broad spectrum therapeutic intervention.

Keywords
AR-12; Antiviral; BIBX; Ebola; Lassa.
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