Dakai Liu,Da Shi,Hongyan Shi,Liaoyuan Zhang,Jiyu Zhang,Miaomiao Zeng,Tingshuai Feng,Xiaoman Yang,Xin Zhang,Jianfei Chen,Zhaoyang Jing,Zhaoyang Ji,Jialin Zhang,Li Feng

Viruses.2023 Dec 11;15(12):2406.doi: 10.3390/v15122406.

Abstract

Swine acute diarrhea syndrome coronavirus (SADS-CoV) is an emerging porcine intestinal coronavirus that can cause acute diarrhea, vomiting, rapid weight loss, and high mortality in newborn piglets. Cholesterol 25-hydroxylase (CH25H) is a molecular mediator of innate antiviral immunity and converts cholesterol to 25-hydroxycholesterol (25HC). Previous studies have reported that CH25H and 25HC have an antiviral effect against multiple viruses. However, the interplay between SADS-CoV infection and CH25H or 25HC is still uncertain. Here, we found that CH25H and its enzymatic product 25HC restrained SADS-CoV replication by blocking membrane fusion. Our results show that CH25H was upregulated by SADS-CoV infection in vitro and in vivo, and that it was an IFN-stimulated gene in porcine ileum epithelial cells. Moreover, CH25H and CH25H mutants lacking catalytic activity can inhibit SADS-CoV replication. Furthermore, 25HC significantly suppressed SADS-CoV infection by inhibiting virus entry. Notably, we confirmed that CH25H and 25HC blocked SADS-CoV spike protein-mediated membrane fusion. Our data provide a possible antiviral therapy against SADS-CoV and other conceivable emerging coronaviruses in the future.

Keywords: SADS-CoV; cholesterol 25-hydroxylase; membrane fusion; spike protein.