Screening antivirals with a mCherry-expressing recombinant bovine respiratory syncytial virus: a proof of concept using cyclopamine

Vet Res. 2023 Apr 17;54(1):36. doi: 10.1186/s13567-023-01165-x.

Abstract

Bovine respiratory syncytial virus (BRSV) is a pathogenic pneumovirus and a major cause of acute respiratory infections in calves. Although different vaccines are available against BRSV, their efficiency remains limited, and no efficient and large-scale treatment exists. Here, we developed a new reverse genetics system for BRSV expressing the red fluorescent protein mCherry, based on a field strain isolated from a sick calf in Sweden. Although this recombinant fluorescent virus replicated slightly less efficiently compared to the wild type virus, both viruses were shown to be sensitive to the natural steroidal alkaloid cyclopamine, which was previously shown to inhibit human RSV replication. Our data thus point to the potential of this recombinant fluorescent BRSV as a powerful tool in preclinical drug discovery to enable high throughput compound screening.

Keywords: Bovine respiratory syncytial virus; antiviral drugs; cyclopamine; mCherry reverse genetics.

MeSH terms

  • Animals
  • Antibodies, Viral
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • Cattle
  • Cattle Diseases*
  • Humans
  • Respiratory Syncytial Virus Infections* / drug therapy
  • Respiratory Syncytial Virus Infections* / veterinary
  • Respiratory Syncytial Virus, Bovine*
  • Respiratory Syncytial Virus, Human* / metabolism

Substances

  • cyclopamine
  • Antiviral Agents
  • Antibodies, Viral