Anti-influenza virus activity of a salcomine derivative mediated by inhibition of viral RNA synthesis

Arch Virol. 2018 Jun;163(6):1607-1614. doi: 10.1007/s00705-018-3779-9. Epub 2018 Mar 1.

Abstract

Influenza virus infection is a major threat to global health. Although vaccines and anti-influenza virus drugs are available, annual influenza virus epidemics result in severe illness, and an influenza pandemic occurs every 20-30 years. To identify candidate anti-influenza virus compounds, we screened approximately 5,000 compounds in an in-house library. We identified MZ7465, a salcomine derivative, as a potent inhibitor of influenza virus propagation. We analyzed the antiviral propagation mechanism of the hit compound by determining the amounts of viral proteins and RNA in infected cells treated with or without the hit compound. Treatment of infected cells with MZ7465 decreased both viral protein and RNA synthesis. In addition, an in vitro assay showed that viral RNA synthesis was directly inhibited by MZ7465. These results suggest that salcomine and its derivatives are potential candidates for the treatment of influenza virus infections.

MeSH terms

  • Animals
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Bronchi / drug effects
  • Bronchi / pathology
  • Bronchi / virology
  • Cell Line
  • Dogs
  • Epithelial Cells / drug effects
  • Epithelial Cells / pathology
  • Epithelial Cells / virology
  • Gene Expression Regulation, Viral
  • HEK293 Cells
  • High-Throughput Screening Assays
  • Humans
  • Influenza A Virus, H1N1 Subtype / drug effects*
  • Influenza A Virus, H1N1 Subtype / genetics
  • Influenza A Virus, H1N1 Subtype / growth & development
  • Influenza A Virus, H3N2 Subtype / drug effects*
  • Influenza A Virus, H3N2 Subtype / genetics
  • Influenza A Virus, H3N2 Subtype / growth & development
  • Madin Darby Canine Kidney Cells
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacology*
  • RNA, Viral / antagonists & inhibitors*
  • RNA, Viral / biosynthesis
  • RNA, Viral / genetics
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology
  • Structure-Activity Relationship
  • Viral Proteins / antagonists & inhibitors*
  • Viral Proteins / biosynthesis
  • Viral Proteins / genetics
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Organometallic Compounds
  • RNA, Viral
  • Small Molecule Libraries
  • Viral Proteins
  • N,N-ethylenebis(salicylideneiminato)cobalt(II)