title: A small molecule multi-kinase inhibitor reduces influenza A virus replication by restricting viral RNA synthesis.
abstract: Currently available drugs against influenza virus target the viral neuraminidase or the M2 ion channel. The emergence of viral strains resistant to these drugs has been widely described; therefore, there is an urgent need for novel antiviral drugs. Targeting of host factors required for viral replication is an attractive option for circumventing the problem of drug resistance. Several RNAi screens have demonstrated that host kinases are required for the replication of influenza virus. To determine whether compounds that inhibit these kinases can impair viral replication, we tested several kinase inhibitors for activity against influenza A virus. We demonstrate that the multi-kinase inhibitor ON108110 reduces replication of influenza A virus in a dose-dependent manner by suppressing viral RNA synthesis. In addition, ON108110 also inhibits other viruses including vesicular stomatitis virus and Newcastle disease virus, suggesting that this compound may represent a novel class of antiviral agents.
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Luis
authors.initials: L
authors.lastname: Martinez-Gil
authors.forename: Judith G
authors.initials: JG
authors.lastname: Alamares-Sapuay
authors.forename: M V
authors.initials: MV
authors.lastname: Ramana Reddy
authors.forename: Peter H
authors.initials: PH
authors.lastname: Goff
authors.forename: E
authors.initials: E
authors.lastname: Premkumar Reddy
authors.forename: Peter
authors.initials: P
authors.lastname: Palese
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects / Q000201:enzymology / Q000235:genetics / Q000502:physiology*; D007251:Influenza, Human / Q000821:virology*; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D012367:RNA, Viral / Q000235:genetics* / Q000378:metabolism; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D047428:Protein Kinase Inhibitors; D012367:RNA, Viral; D014764:Viral Proteins; C487630:NA protein, influenza A virus; D009439:Neuraminidase
keywords: Influenza virus; Kinase inhibitor; Viral RNA synthesis