Effect of Vandetanib on Andes virus survival in the hamster model of Hantavirus pulmonary syndrome

Antiviral Res. 2016 Aug:132:66-9. doi: 10.1016/j.antiviral.2016.05.014. Epub 2016 May 24.

Abstract

Hantavirus pulmonary syndrome (HPS) is a severe disease caused by hantavirus infection of pulmonary microvascular endothelial cells leading to microvascular leakage, pulmonary edema, pleural effusion and high case fatality. Previously, we demonstrated that Andes virus (ANDV) infection caused up-regulation of vascular endothelial growth factor (VEGF) and concomitant downregulation of the cellular adhesion molecule VE-cadherin leading to increased permeability. Analyses of human HPS-patient sera have further demonstrated increased circulating levels of VEGF. Here we investigate the impact of a small molecule antagonist of the VEGF receptor 2 (VEGFR-2) activation in vitro, and overall impact on survival in the Syrian hamster model of HPS.

Keywords: Andes virus; Animal model; Antiviral; Bunyaviridae; Hantavirus pulmonary syndrome; Hemorrhagic fever; Tyrosine kinase inhibitor; Vandetanib; Vascular endothelial growth factor.

MeSH terms

  • Animals
  • Capillary Permeability / drug effects
  • Cricetinae
  • Disease Models, Animal
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Endothelial Cells / virology
  • Hantavirus Pulmonary Syndrome / metabolism
  • Hantavirus Pulmonary Syndrome / mortality
  • Hantavirus Pulmonary Syndrome / virology*
  • Orthohantavirus / drug effects*
  • Orthohantavirus / physiology*
  • Phosphorylation / drug effects
  • Piperidines / pharmacology*
  • Protein Kinase Inhibitors / pharmacology*
  • Quinazolines / pharmacology*
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A / metabolism
  • Viral Load

Substances

  • Piperidines
  • Protein Kinase Inhibitors
  • Quinazolines
  • Vascular Endothelial Growth Factor A
  • vandetanib