Imipramine inhibits feline infectious peritonitis virus infection by targeting host cholesterol metabolism via NPC1.

Authors

Rui Jing, Yao Yao, Yuhan Li, Shuo Zheng, Hongxuan Li, Li Kang, Li Gao, Pinghuang Liu

Published in

Antimicrobial agents and chemotherapy. Pages e0186625. Jun 23, 2026. Epub Jun 23, 2026.

Abstract

Feline infectious peritonitis (FIP), a fatal disease caused by FIP virus (FIPV), currently lacks effective vaccines and treatments. Imipramine, a tricyclic antidepressant with known broad-spectrum antiviral properties, was investigated for its efficacy against FIPV. Our in vitro studies demonstrated that imipramine inhibits FIPV infection in a dose-dependent manner, with a high selectivity index (SI = 291) and maximal effect when administered during co-treatment. Time-of-addition assays revealed that imipramine acts at multiple stages, interfering with both viral entry and replication. Mechanistically, we found that imipramine targets the host protein Niemann-Pick C1 (NPC1), disrupting cholesterol metabolism to block viral entry. It also independently suppresses FIPV-induced pro-inflammatory cytokine production without relying on type I interferon signaling. Notably, in an in vivo model, imipramine treatment reduced viral loads and alleviated clinical signs in FIPV-infected cats. These findings collectively identify imipramine as a promising, host-targeted therapeutic candidate for FIP.

PMID:
42365506
Bibliographic data and abstract were imported from PubMed on 28 Jun 2026.

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