Novel influenza polymerase PB2 inhibitors for the treatment of influenza A infection

Bioorg Med Chem Lett. 2019 Oct 15;29(20):126639. doi: 10.1016/j.bmcl.2019.126639. Epub 2019 Aug 24.

Abstract

Exploration of the chemical space of known influenza polymerase PB2 inhibitor Pimodivir, was performed by our group. We synthesized and identified compounds 16a and 16b, two novel thienopyrimidine derivatives displaying anti-influenza A activity in the single digit nanomolar range in cell culture. Binding of these unique compounds in the influenza polymerase PB2 pocket was also determined using molecular modeling.

Keywords: Antiviral; Flu; Influenza A; Virus.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • A549 Cells
  • Amino Acid Sequence
  • Animals
  • Antiviral Agents / chemistry*
  • Antiviral Agents / pharmacology
  • Drug Discovery
  • Humans
  • Influenza A virus / drug effects*
  • Influenza, Human / drug therapy*
  • Models, Molecular
  • Molecular Structure
  • Protein Binding
  • Pyridines / chemistry*
  • Pyridines / pharmacology
  • Pyrimidines / chemistry*
  • Pyrimidines / pharmacology
  • Pyrroles / chemistry*
  • Pyrroles / pharmacology
  • RNA-Dependent RNA Polymerase / metabolism*
  • Structure-Activity Relationship
  • Viral Proteins / metabolism*
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • PB2 protein, Influenzavirus A
  • Pyridines
  • Pyrimidines
  • Pyrroles
  • Viral Proteins
  • pimodivir
  • RNA-Dependent RNA Polymerase