Ionophore Antibiotics Inhibit Type II Feline Coronavirus Proliferation In Vitro

Viruses. 2022 Aug 6;14(8):1734. doi: 10.3390/v14081734.

Abstract

Feline coronaviruses (FCoVs) infect cats worldwide and cause severe systemic diseases, such as feline infectious peritonitis (FIP). FIP has a high mortality rate, and drugs approved by the Food and Drug Administration have been ineffective for the treatment of FIP. Investigating host factors and the functions required for FCoV replication is necessary to develop effective drugs for the treatment of FIP. FCoV utilizes an endosomal trafficking system for cellular entry after binding between the viral spike (S) protein and its receptor. The cellular enzymes that cleave the S protein of FCoV to release the viral genome into the cytosol require an acidic pH optimized in the endosomes by regulating cellular ion concentrations. Ionophore antibiotics are compounds that form complexes with alkali ions to alter the endosomal pH conditions. This study shows that ionophore antibiotics, including valinomycin, salinomycin, and nigericin, inhibit FCoV proliferation in vitro in a dose-dependent manner. These results suggest that ionophore antibiotics should be investigated further as potential broad-spectrum anti-FCoV agents.

Keywords: cats; feline coronavirus; feline infectious peritonitis; ionophore antibiotics; nigericin; salinomycin; valinomycin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Cats
  • Cell Proliferation
  • Coronavirus, Feline* / genetics
  • Feline Infectious Peritonitis* / drug therapy
  • Ionophores / pharmacology

Substances

  • Anti-Bacterial Agents
  • Ionophores

Grants and funding

This work was supported by a Grant-in-Aid for Scientific Research (B); grant number JP (21H02374), JSPS KAKENHI.