Garcinol from Garcinia indica inhibits HIV-1 reverse transcriptase-associated ribonuclease H

Arch Pharm (Weinheim). 2021 Sep;354(9):e2100123. doi: 10.1002/ardp.202100123. Epub 2021 May 18.

Abstract

The bioactive components of Garcinia indica, garcinol (camboginol), and isogarcinol (cambogin), are suitable drug candidates for the treatment of various human diseases. HIV-1-RNase H assay was used to study the RNase H inhibition by garcinol and isogarcinol. Docking of garcinol into the active site of the enzyme was carried out to rationalize the difference in activities between the two compounds. Garcinol showed higher HIV-1-RNase H inhibition than the known inhibitor RDS1759 and retained full potency against the RNase H of a drug-resistant HIV-1 reverse transcriptase form. Isogarcinol was distinctly less active than garcinol, indicating the importance of the enolizable β-diketone moiety of garcinol for anti-RNase H activity. Docking calculations confirmed these findings and suggested this moiety to be involved in the chelation of metal ions of the active site. On the basis of its HIV-1 reverse transcriptase-associated RNase H inhibitory activity, garcinol is worth being further explored concerning its potential as a cost-effective treatment for HIV patients.

Keywords: Garcinia indica; HIV; RNase H; antiviral drugs; garcinol.

Publication types

  • Comparative Study

MeSH terms

  • Garcinia / chemistry*
  • HIV Infections / drug therapy
  • HIV Infections / virology
  • HIV-1 / drug effects
  • HIV-1 / enzymology
  • Molecular Docking Simulation
  • Reverse Transcriptase Inhibitors / isolation & purification
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Ribonuclease H, Human Immunodeficiency Virus / antagonists & inhibitors*
  • Terpenes / isolation & purification
  • Terpenes / pharmacology*

Substances

  • Reverse Transcriptase Inhibitors
  • Terpenes
  • isogarcinol
  • Ribonuclease H, Human Immunodeficiency Virus
  • garcinol