CCR5/CXCR4 Dual Antagonism for the Improvement of HIV Infection Therapy

Molecules. 2019 Feb 2;24(3):550. doi: 10.3390/molecules24030550.

Abstract

HIV entry in the host cell requires the interaction with the CD4 membrane receptor, and depends on the activation of one or both co-receptors CCR5 and CXCR4. Former selective co-receptor antagonists, acting at early stages of infection, are able to impair the receptor functions, preventing the viral spread toward AIDS. Due to the capability of HIV to develop resistance by switching from CCR5 to CXCR4, dual co-receptor antagonists could represent the next generation of AIDS prophylaxis drugs. We herein present a survey on relevant results published in the last few years on compounds acting simultaneously on both co-receptors, potentially useful as preventing agents or in combination with classical anti-retroviral drugs based therapy.

Keywords: AIDS; HIV entry; chemokine receptors; dual drugs.

Publication types

  • Review

MeSH terms

  • Anti-HIV Agents / chemistry*
  • Anti-HIV Agents / therapeutic use
  • Benzylamines
  • CCR5 Receptor Antagonists / chemistry
  • CCR5 Receptor Antagonists / therapeutic use
  • Cyclams
  • HIV Infections / drug therapy*
  • HIV Infections / genetics
  • HIV Infections / virology
  • HIV-1 / drug effects
  • Heterocyclic Compounds / chemistry
  • Heterocyclic Compounds / therapeutic use
  • Humans
  • Maraviroc / chemistry
  • Maraviroc / therapeutic use
  • Pyridines / chemistry
  • Pyridines / therapeutic use
  • Receptors, CCR5 / drug effects*
  • Receptors, CCR5 / genetics
  • Receptors, CXCR4 / antagonists & inhibitors*
  • Receptors, CXCR4 / genetics

Substances

  • 1-((2,6-dichloropyridin-4-yl)methyl)-1,4,8,11-tetrazacyclotetradecane
  • Anti-HIV Agents
  • Benzylamines
  • CCR5 Receptor Antagonists
  • CCR5 protein, human
  • CXCR4 protein, human
  • Cyclams
  • Heterocyclic Compounds
  • Pyridines
  • Receptors, CCR5
  • Receptors, CXCR4
  • Maraviroc
  • plerixafor