PF-00835231 broadly inhibits swine Alpha-coronavirus, including emerging SADS-CoV

文献类型： 外文期刊

第一作者： Shi, Lei

作者： Shi, Lei;Duan, Yueyue;Cao, Liyan;Zhang, Yu;Yuan, Cong;Sun, Maowen;Zhang, Juan;Kong, Xiangyu;Zheng, Haixue;Wang, Qi;Shi, Lei;Duan, Yueyue;Cao, Liyan;Zhang, Yu;Yuan, Cong;Sun, Maowen;Zhang, Juan;Kong, Xiangyu;Wang, Qi;Shi, Lei;Duan, Yueyue;Cao, Liyan;Zhang, Yu;Yuan, Cong;Sun, Maowen;Zhang, Juan;Kong, Xiangyu;Wang, Qi

作者机构：

关键词： Alpha-coronavirus

期刊名称：JOURNAL OF VIROLOGY （ 影响因子：3.8； 五年影响因子：3.9 ）

ISSN： 0022-538X

年卷期： 2024 年 98 卷 11 期

页码：

收录情况： SCI

摘要： Swine Alpha-coronaviruses are one of the most destructive pathogens affecting the swine industries across the world. Swine Alpha-coronaviruses include transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus, porcine respiratory coronavirus, and swine acute diarrhea syndrome coronavirus (SADS-CoV). Thus far, swine Alpha-coronaviruses treatment options are very limited. Therefore, the identification of safe and effective treatment of swine Alpha-coronaviruses is urgently needed. In the current study, we screened a library of 240 FDA-approved compounds for antiviral activity against TGEV. Among screening, the 3CL protease inhibitor PF-00835231 was shown to dramatically inhibit TGEV replication in vitro systems. Mechanistically, PF-00835231 inhibits nonstructural protein 5 (Nsp5) protease activity targeting the cleavage at Nsp5-Nsp6 of TGEV. Additionally, PF-00835231 exhibited the potent broad-spectrum swine Alpha-coronaviruses antiviral activity. Treatment of PF-00835231 in mice not only blocks SADS-CoV deadly infection but also dramatically reduces viral copies. Taken together, our study provides evidence that PF-00835231 may control of the current swine Alpha-coronaviruses and emerging swine Alpha-coronaviruses in the future.

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