The use of a topical protease inhibitor, Saquinavir, to alleviate mouse papillomavirus-mediated anal disease

Virology. 2022 Nov:576:96-104. doi: 10.1016/j.virol.2022.09.012. Epub 2022 Sep 29.

Abstract

Select protease inhibitors (PI) have been found to be effective in decreasing human papillomavirus oncoprotein expression. This study evaluated whether the topical PI, Saquinavir (SQV), promotes viral clearance in an infectious mouse model with Mus musculus papillomavirus 1 (MmuPV1). NOD scid gamma (NSG) mice were anally infected with ∼4 × 108 viral genome equivalents of MmuPV1 and 120 days post-infection (when majority have high-grade anal dysplasia), began topical treatments: control (mock), 7,12-dimethylbenz(a)anthracene (DMBA) only, once weekly to promote carcinogenesis, 1% SQV only, daily (Monday - Friday), and SQV + DMBA. Viral MmuPV1 load was analyzed from anal lavages pre and post-treatment. Anal tissue was harvested, processed, and evaluated for drug absorption, grade of anal disease, and anal viral RNA. Results suggest that topical SQV promotes decreased viral shedding in female mice treated with SQV.

Keywords: Anal cancer; Anal dysplasia; Mouse papillomavirus; Protease inhibitors; Squamous cell carcinoma; Viral clearance.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anthracenes
  • Enzyme Inhibitors
  • Female
  • HIV Infections*
  • HIV Protease Inhibitors* / therapeutic use
  • Humans
  • Mice
  • Papillomaviridae / genetics
  • RNA, Viral
  • Saquinavir / pharmacology
  • Saquinavir / therapeutic use
  • Viral Load
  • Virus Diseases*

Substances

  • Saquinavir
  • HIV Protease Inhibitors
  • RNA, Viral
  • Enzyme Inhibitors
  • Anthracenes