Update on Recent Developments in Small Molecular HIV-1 RNase H Inhibitors (2013-2016): Opportunities and Challenges

Curr Med Chem. 2018;25(14):1682-1702. doi: 10.2174/0929867324666170113110839.

Abstract

Combinations of antiretroviral drugs are successfully used to treat HIV-infected patients. However, drug resistance is a major problem that makes discovery of new antiretroviral drugs an ongoing priority. The ribonuclease H (RNase H) activity of the HIV-1 reverse transcriptase catalyzes the selective hydrolysis of the RNA strand of RNA:DNA heteroduplex replication intermediates, and represents an attractive unexploited target for drug development. This review reports on recent progress in the characterization of HIV-1 RNase H inhibitors from 2013 to 2016, describing their chemical structures, structureactivity relationship and binding modes. Focus is given to emerging medicinal chemistry principles and insights into the discovery and development of RNase H inhibitors.

Keywords: AIDS; HIV-1; RNase H inhibitors; SAR; antiviral; drug design; dual inhibitors; metalloenzyme..

Publication types

  • Review

MeSH terms

  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology*
  • Cell Line, Tumor
  • Drug Design
  • HIV-1 / metabolism
  • Humans
  • Reverse Transcriptase Inhibitors / chemistry
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Ribonuclease H, Human Immunodeficiency Virus / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • Anti-HIV Agents
  • Reverse Transcriptase Inhibitors
  • Ribonuclease H, Human Immunodeficiency Virus