Identification of a receptor tyrosine kinase inhibitor CP-724714 inhibits SADS-CoV related swine diarrhea coronaviruses infection in vitro  

作　　者：Ling Zhou Cheng Li Ruiyu Zhang Qianniu Li Yuan Sun Yaoyu Feng Tian Lan Jingyun Ma 

机构地区：[1]Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding,College of Animal Science,South China Agricultural University,Guangzhou,510642,China [2]Guangdong Laboratory for Lingnan Modern Agriculture,Guangzhou,510642,China

出　　处：《Virologica Sinica》2023年第5期778-786,共9页中国病毒学（英文版）

基　　金：This work was funded by the Guangdong Major Project of Basic and Applied Basic Research(No.2020B0301030007);the Natural Science Foundation of Guangdong Province(2022A1515012473,2020A1515010220);the Science and Technology Program of Guangzhou City of China(2023B03J1310.)。

摘　　要：The outbreak of the COVID-19 epidemic in 2020 has caused unprecedented panic among all mankind,pointing the major importance of effective treatment.Since the emergence of the swine acute diarrhea syndrome coronavirus(SADS-CoV)at the end of 2017,multiple reports have indicated that the bat-related SADS-CoV possesses a potential threat for cross-species transmission.Vaccines and antiviral drugs development deserve more attention.In this study,we found that the HER2 phosphorylation inhibitor(CP-724714)inhibited SADS-CoV infection in a dose-dependent manner.Further validation demonstrated that CP-724714 affected at the post-entry stage of SADS-CoV infection cycle.Also,efficient SADS-CoV infection required the activation of HER2 and its cascade Ras-Raf-Mek-Erk signaling pathway.In addition,CP-724714 has a broad-spectrum anti-swine diarrhea coronaviruses activity,and can dose-dependently combat SADS-CoV,porcine epidemic diarrhea virus(PEDV),porcine deltacoronavirus(PDCoV)and transmissible gastroenteritis virus(TGEV)infection in vitro with a specificity index of greater than 21.98,9.38,95.23 and 31.62,respectively.These results highlight the potential utility of CP-724714 or antiviral drugs targeting with HER2 and its cascade Ras-Raf-Mek-Erk signaling pathway as host-targeted SADS-CoV and other related coronaviruses therapeutics.

关 键 词：SADS-CoV CORONAVIRUS Antiviral agents HER2 CP-724714 

分 类 号：S859.7[农业科学—临床兽医学]