Methyl brevifolincarboxylate, a novel influenza virus PB2 inhibitor from Canarium Album (Lour.) Raeusch

Chem Biol Drug Des. 2020 Nov;96(5):1280-1291. doi: 10.1111/cbdd.13740. Epub 2020 Jun 25.

Abstract

Methyl brevifolincarboxylate (MBC) was isolated from ethyl acetate extract of Canarium album (Lour.) Raeusch. The structure was identified, and the effect on influenza A virus infection was evaluated. MBC exhibited inhibitory activity against influenza virus A/Puerto Rico/8/34 (H1N1) and A/Aichi/2/68 (H3N2) with IC50 values of 27.16 ± 1.39 μM and 33.41 ± 2.34 μM. Mechanism studies indicated that MBC inhibited the replication of influenza A virus by targeting PB2 cap-binding domain. Our results demonstrated MBC was a potent PB2 cap-binding inhibitor and represented as a new type of promising lead compound for the development of anti-influenza virus drugs from natural products.

Keywords: Canarium album (Lour.) Raeusch; PB2 cap-binding inhibitor; influenza A virus; methyl brevifolincarboxylate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology*
  • Benzopyrans / pharmacology*
  • Burseraceae / chemistry*
  • Chick Embryo
  • Dogs
  • HEK293 Cells
  • Humans
  • Influenza A Virus, H1N1 Subtype / drug effects*
  • Influenza A Virus, H3N2 Subtype / drug effects*
  • Madin Darby Canine Kidney Cells
  • Microbial Sensitivity Tests
  • RNA-Dependent RNA Polymerase / antagonists & inhibitors*
  • Real-Time Polymerase Chain Reaction
  • Viral Proteins / antagonists & inhibitors*

Substances

  • Antiviral Agents
  • Benzopyrans
  • PB2 protein, Influenzavirus A
  • Viral Proteins
  • methyl brevifolincarboxylate
  • RNA-Dependent RNA Polymerase