Inhibition of Orbivirus Replication by Aurintricarboxylic Acid

Int J Mol Sci. 2020 Oct 2;21(19):7294. doi: 10.3390/ijms21197294.

Abstract

Bluetongue virus (BTV) and African horse sickness virus (AHSV) are vector-borne viruses belonging to the Orbivirus genus, which are transmitted between hosts primarily by biting midges of the genus Culicoides. With recent BTV and AHSV outbreaks causing epidemics and important economy losses, there is a pressing need for efficacious drugs to treat and control the spread of these infections. The polyanionic aromatic compound aurintricarboxylic acid (ATA) has been shown to have a broad-spectrum antiviral activity. Here, we evaluated ATA as a potential antiviral compound against Orbivirus infections in both mammalian and insect cells. Notably, ATA was able to prevent the replication of BTV and AHSV in both cell types in a time- and concentration-dependent manner. In addition, we evaluated the effect of ATA in vivo using a mouse model of infection. ATA did not protect mice against a lethal challenge with BTV or AHSV, most probably due to the in vivo effect of ATA on immune system regulation. Overall, these results demonstrate that ATA has inhibitory activity against Orbivirus replication in vitro, but further in vivo analysis will be required before considering it as a potential therapy for future clinical evaluation.

Keywords: Orbivirus, Arbovirus, Bluetongue virus, African horse sickness virus, aurintricarboxylic acid, antiviral..

MeSH terms

  • African Horse Sickness / drug therapy
  • African Horse Sickness / genetics
  • African Horse Sickness / virology
  • African Horse Sickness Virus / drug effects*
  • African Horse Sickness Virus / genetics
  • African Horse Sickness Virus / pathogenicity
  • Animals
  • Aurintricarboxylic Acid / pharmacokinetics*
  • Bluetongue virus / drug effects*
  • Bluetongue virus / genetics
  • Bluetongue virus / pathogenicity
  • Ceratopogonidae / pathogenicity
  • Ceratopogonidae / virology
  • Horses / virology
  • Sheep / virology
  • Virus Diseases / drug therapy*
  • Virus Diseases / genetics
  • Virus Diseases / virology
  • Virus Replication / drug effects

Substances

  • Aurintricarboxylic Acid