Uvaria angolensis as a promising source of inhibitors of HIV-1 RT-associated RNA-dependent DNA polymerase and RNase H functions

Nat Prod Res. 2018 Mar;32(6):640-647. doi: 10.1080/14786419.2017.1332615. Epub 2017 May 25.

Abstract

Reverse transcriptase (RT)-associated DNA polymerase (RDDP) and ribonucleaser H (RNase H) functions are both essential for HIV-1 genome replication, and the identification of new inhibitors to block both of them is a goal actively pursued by the scientific community. In this field, natural extracts have shown a great potential as source of new antivirals. In the present work, we investigated the effect of Uvaria angolensis extracts on the HIV-1 reverse transcriptase-associated DNA polymerase and ribonuclease H activities. The U. angolensis stem bark methanol extract inhibit both HIV-1 RNase H function and RDDP activity with IC50 values of 1.0 ± 0.2 and 0.62 ± 0.15 μg/mL, respectively and, after been fractionated with different solvents, its solid residue showed an IC50 of 0.10 ± 0.03 and of 0.23 ± 0.04 μg/mL against RNase H and RDDP, respectively, hence laying the bases for further studies for identification of single active components.

Keywords: HIV-1; Uvaria angolensis; dual inhibitor; plant extracts; reverse transcriptase.

MeSH terms

  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology*
  • Cell Line
  • Chemical Fractionation
  • Drug Evaluation, Preclinical / methods
  • HIV Reverse Transcriptase / antagonists & inhibitors*
  • Humans
  • Inhibitory Concentration 50
  • Plant Bark / chemistry
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology
  • RNA-Directed DNA Polymerase / metabolism
  • Reverse Transcriptase Inhibitors / chemistry
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Ribonuclease H / antagonists & inhibitors*
  • Uvaria / chemistry*

Substances

  • Anti-HIV Agents
  • Plant Extracts
  • Reverse Transcriptase Inhibitors
  • reverse transcriptase, Human immunodeficiency virus 1
  • HIV Reverse Transcriptase
  • RNA-Directed DNA Polymerase
  • Ribonuclease H