Abstract
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.
基金项目
Guangdong Major Project of Basic and Applied Basic Research(2020B0301030007)
Natural Science Foundation of Guangdong Province(2022A1515012473)
Natural Science Foundation of Guangdong Province(2020A1515010220)
Science and Technology Program of Guangzhou City of China(2023B03J1310)
NETL
NSTL
万方数据