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

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

Publication date: Aug 05, 2026

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.

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Concepts Keywords
Cats Animals
Cholesterol Antiviral Agents
Host Antiviral Agents
Niemann Cats
Vaccines Cell Line
Cholesterol
Cholesterol
cholesterol metabolism
Coronavirus, Feline
Feline Infectious Peritonitis
FIPV
Imipramine
Imipramine
imipramine
Niemann-Pick C1 Protein
Niemann-Pick C1 Protein
NPC1
Viral Load
Virus Internalization
Virus Replication

Semantics

Type Source Name
drug DRUGBANK Imipramine
disease MESH feline infectious peritonitis
disease MESH virus infection
pathway KEGG Cholesterol metabolism
disease MESH NPC1
disease MESH infection
drug DRUGBANK Cholesterol

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