Identification of a receptor tyrosine kinase inhibitor CP-724714 inhibits SADS-CoV related swine diarrhea coronaviruses infection in vitro
- Virol Sin. 2023 Jul 3;S1995-820X(23)00079-2. doi: 10.1016/j.virs.2023.06.010.
- 1. Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China; Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, 510642, China.
- 2. Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, 510642, China.
- 3. Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China; Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, 510642, China. Electronic address: [email protected].
- 4. Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China; Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, 510642, China. Electronic address: [email protected].
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.