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Nanoparticulate Vacuolar ATPase Blocker Exhibits Potent Host-Targeted Antiviral Activity Against Feline Coronavirus

Che-Ming Jack Hu, Wei-Shan Chang, Zih-Syun Fang, You-Ting Chen, Wen-Lin Wang, Hsiao-Han Tsai, Ling-Ling Chueh, Tomomi Takano, Tsutomu Hohdatsu, Hui-Wen Chen

Sci Rep. 2017 Oct 12;7(1):13043.

PMID: 29026122

Abstract:

Feline infectious peritonitis (FIP), caused by a mutated feline coronavirus, is one of the most serious and fatal viral diseases in cats. The disease remains incurable, and there is no effective vaccine available. In light of the pathogenic mechanism of feline coronavirus that relies on endosomal acidification for cytoplasmic entry, a novel vacuolar ATPase blocker, diphyllin, and its nanoformulation are herein investigated for their antiviral activity against the type II feline infectious peritonitis virus (FIPV). Experimental results show that diphyllin dose-dependently inhibits endosomal acidification in fcwf-4 cells, alters the cellular susceptibility to FIPV, and inhibits the downstream virus replication. In addition, diphyllin delivered by polymeric nanoparticles consisting of poly(ethylene glycol)-block-poly(lactide-co-glycolide) (PEG-PLGA) further demonstrates an improved safety profile and enhanced inhibitory activity against FIPV. In an in vitro model of antibody-dependent enhancement of FIPV infection, diphyllin nanoparticles showed a prominent antiviral effect against the feline coronavirus. In addition, the diphyllin nanoparticles were well tolerated in mice following high-dose intravenous administration. This study highlights the therapeutic potential of diphyllin and its nanoformulation for the treatment of FIP.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP22055227 Diphyllin Diphyllin 22055-22-7 Price
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