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Besides the limited development of antiviral drugs that mainly target virus proteins, concerns about resistance to mutant strains \u2013 similar to those seen in human and other mammalian viruses \u2013 remain high. Therefore, addressing these challenges involves developing innovative antiviral therapies, such as host-directed treatments that target host cell processes essential for viral replication. FIPV infection induced distinctive dynamics of lipid droplet (LD) remodelling, characterized by an increase in LD abundance from early to mid-infection, followed by a subsequent decline. Phosphorylated hormone-sensitive lipase, a key mediator of LD hydrolysis and fatty-acid release, became activated after the mid-infection phase, potentially contributing to elevated intracellular fatty-acid availability during late infection. Notably, atglistatin (DABPU-DM) and its derivatives robustly suppressed FIPV replication in Crandell\u2013Rees feline kidney (CRFK) and feline macrophage Fcwf-4 cells, coincident with preservation of LD integrity and inhibition of LD breakdown. Among these compounds, DABPU-DE had the best selectivity index (686.0\u00b135.2) against FIPV, with a higher half-maximal cytotoxic concentration (274.4\u00b13.6\u2009\u00b5M) and a lower half-maximal inhibitory concentration (0.4\u00b10.02\u2009\u00b5M). Moreover, combining DABPU-DE (0.18\u2009\u00b5M) with remdesivir (1.35\u2009\u00b5M), a viral RNA-dependent RNA polymerase inhibitor, showed a very strong synergistic effect (CI=0.09\u2009and Bliss synergy score=14.46\u00b11.80) in inhibiting FIPV replication in CRFK cells, even at lower doses than either drug alone. In conclusion, DABPU-DE is a promising antiviral candidate for FIPV, and its synergistic effect with remdesivir warrants further research in cats infected with FIPV.<\/jats:p>","DOI":"10.1099\/jgv.0.002261","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T16:17:27Z","timestamp":1776874647000},"source":"Crossref","is-referenced-by-count":1,"title":["Synergistic antiviral effect of host Adipose Triglyceride Lipase-directed DABPU-DE with coronavirus RNA-dependent RNA polymerase-targeting remdesivir on feline infectious peritonitis virus"],"prefix":"10.1099","volume":"107","author":[{"given":"Shaimaa","family":"Aboelmagd","sequence":"first","affiliation":[{"name":"Department of Zoonoses, Faculty of Veterinary Medicine, Assiut University, Assiut, Egypt"},{"name":"Host-Directed Antiviral Research Center, Chonnam National University, Gwangju 61186, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seok 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