Identification of a novel type of small molecule inhibitor against HIV-1

BMB Rep. 2015 Feb;48(2):121-6. doi: 10.5483/bmbrep.2015.48.2.239.

Abstract

Here we report a new chemical inhibitor against HIV-1 with a novel structure and mode of action. The inhibitor, designated as A1836, inhibited HIV-1 replication and virus production with a 50% inhibitory concentration (IC₅₀) of 2.0 μM in an MT-4 cell-based and cytopathic protection antiviral assay, while its 50% cytotoxic concentration (CC₅₀) was much higher than 50 μM. Examination of the effect of A1836 on in vitro HIV-1 reverse transcriptase (RT) and integrase showed that neither were molecular targets of A1836. The characterization and re-infection assay of the HIV-1 virions generated in the presence of A1836 showed that the synthesis of early RT products in the cells infected with the virions was inhibited dose-dependently, due in part to abnormal protein formation within the virions, thus resulting in an impaired infectivity. These results suggest that A1836 might be a novel candidate for the development of a new type of HIV-1 inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • HEK293 Cells
  • HIV Integrase / metabolism
  • HIV Reverse Transcriptase / metabolism
  • HIV-1 / genetics
  • HIV-1 / physiology*
  • Humans
  • Plasmids / metabolism
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology*
  • Transfection
  • Virus Replication / drug effects*

Substances

  • (1-(4-chlorobenzyl)-N-(2-methoxybenzyl)-1H-pyrazole-3-carboxamide
  • Antiviral Agents
  • Pyrazoles
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • HIV Integrase
  • reverse transcriptase, Human immunodeficiency virus 1
  • HIV Reverse Transcriptase