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

Emma L Mohr; Laura K McMullan; Michael K Lo; Jessica R Spengler; Éric Bergeron; César G Albariño; Punya Shrivastava-Ranjan; Cheng-Feng Chiang; Stuart T Nichol; Christina F Spiropoulou; Mike Flint

doi:10.1016/j.antiviral.2015.05.003

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. Epub 2015 May 16.

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.

Published by Elsevier B.V.

MeSH terms

Animals
Antiviral Agents / metabolism*
Arenaviridae / physiology*
Cell Line
Filoviridae / physiology*
Humans
Nipah Virus / physiology*
Phosphotransferases / antagonists & inhibitors*
Virus Internalization / drug effects*
Virus Replication / drug effects*

Substances

Antiviral Agents
Phosphotransferases