Structure-based virtual screening and drug repurposing studies indicate potential inhibitors of bovine papillomavirus E6 oncoprotein

Microbiol Immunol. 2024 Dec;68(12):414-426. doi: 10.1111/1348-0421.13178. Epub 2024 Oct 28.

Abstract

Bovine papillomavirus type 1 (BPV1) is an oncogenic virus that causes lesions and cancer in infected cattle. Despite being one of the most studied genotypes in the family and occurring in herds worldwide, there are currently no vaccines or drugs for its control. The viral E6 oncoprotein plays a crucial role in infection by this virus, making it a promising target for the development of new therapies. In this regard, we integrated structure-based virtual screening approaches, drug repositioning, and molecular dynamics to identify approved drugs with the potential to inhibit BPV1 E6. Our results reveal that Lumacaftor and MK-3207 are promising candidates for controlling BPV1 infection. The findings of this study may contribute to the development of E6 oncoprotein blockers in an accelerated and cost-effective manner.

Keywords: E6; bovine papillomavirus; drug repositioning; molecular dynamics; virtual screening.

MeSH terms

  • Animals
  • Antiviral Agents* / pharmacology
  • Benzodioxoles / pharmacology
  • Bovine papillomavirus 1* / drug effects
  • Bovine papillomavirus 1* / genetics
  • Cattle
  • Cattle Diseases / drug therapy
  • Cattle Diseases / virology
  • Drug Evaluation, Preclinical / methods
  • Drug Repositioning*
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Oncogene Proteins, Viral* / antagonists & inhibitors
  • Oncogene Proteins, Viral* / genetics
  • Papillomavirus Infections* / drug therapy
  • Papillomavirus Infections* / virology
  • Repressor Proteins / antagonists & inhibitors
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism

Substances

  • Oncogene Proteins, Viral
  • Antiviral Agents
  • protein E6, Bovine papillomavirus
  • Repressor Proteins
  • Benzodioxoles