Inhibition of Human Immunodeficiency Virus Type 1 Entry by a Keggin Polyoxometalate

Viruses. 2018 May 16;10(5):265. doi: 10.3390/v10050265.

Abstract

Here, we report the anti-human immunodeficiency virus (HIV) potency and underlying mechanisms of a Keggin polyoxometalate (PT-1, K₆HPTi₂W10O40). Our findings showed that PT-1 exhibited highly potent effects against a diverse group of HIV type 1 (HIV-1) strains and displayed low cytotoxicity and genotoxicity. The time-addition assay revealed that PT-1 acted at an early stage of infection, and these findings were supported by the observation that PT-1 had more potency against Env-pseudotyped virus than vesicular stomatitis virus glycoprotein (VSVG) pseudotyped virus. Surface plasmon resonance binding assays and flow cytometry analysis showed that PT-1 blocked the gp120 binding site in the CD4 receptor. Moreover, PT-1 bound directly to gp41 NHR (N36 peptide), thereby interrupting the core bundle formation of gp41. In conclusion, our data suggested that PT-1 may be developed as a new anti-HIV-1 agent through its effects on entry inhibition.

Keywords: CD4; Keggin polyoxometalate; entry inhibition; gp41 NHR; human immunodeficiency virus type 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Antiviral Agents / toxicity
  • CD4 Antigens / metabolism
  • Cell Survival / drug effects
  • Cells, Cultured
  • Flow Cytometry
  • HIV Envelope Protein gp120 / metabolism
  • HIV Envelope Protein gp41 / biosynthesis
  • HIV Envelope Protein gp41 / chemistry
  • HIV Envelope Protein gp41 / metabolism
  • HIV-1 / drug effects*
  • HIV-1 / physiology
  • Humans
  • Male
  • Mice
  • Peptide Fragments / metabolism
  • Protein Binding / drug effects
  • Surface Plasmon Resonance
  • Titanium / chemistry*
  • Tungsten Compounds / chemistry
  • Tungsten Compounds / pharmacology*
  • Tungsten Compounds / toxicity
  • Virus Internalization / drug effects*

Substances

  • Antiviral Agents
  • CD4 Antigens
  • HIV Envelope Protein gp120
  • HIV Envelope Protein gp41
  • Peptide Fragments
  • Tungsten Compounds
  • gp120 protein, Human immunodeficiency virus 1
  • gp41 protein, Human immunodeficiency virus 1
  • peptide N36
  • Titanium