HSP90 inhibitors 17-AAG and VER-82576 inhibit porcine deltacoronavirus replication in vitro

  • Vet Microbiol. 2022 Feb:265:109316. doi: 10.1016/j.vetmic.2021.109316.
Yujia Zhao  1 ,  Dai Xiao  2 ,  Luwen Zhang  3 ,  Daili Song  4 ,  Rui Chen  5 ,  Shiqian Li  6 ,  Yijie Liao  7 ,  Yimin Wen  8 ,  Weizhe Liu  9 ,  Enbo Yu  10 ,  Yiping Wen  11 ,  Rui Wu  12 ,  Qin Zhao  13 ,  Senyan Du  14 ,  Xintian Wen  15 ,  Sanjie Cao  16 ,  Xiaobo Huang  17
Affiliations
  • 1. Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 611130, China. Electronic address: [email protected].
  • 2. Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 611130, China. Electronic address: [email protected].
  • 3. Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 611130, China. Electronic address: [email protected].
  • 4. Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 611130, China. Electronic address: [email protected].
  • 5. Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 611130, China. Electronic address: [email protected].
  • 6. Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 611130, China. Electronic address: [email protected].
  • 7. Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 611130, China. Electronic address: [email protected].
  • 8. Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 611130, China. Electronic address: [email protected].
  • 9. Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 611130, China. Electronic address: [email protected].
  • 10. Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 611130, China. Electronic address: [email protected].
  • 11. Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 611130, China. Electronic address: [email protected].
  • 12. Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 611130, China. Electronic address: [email protected].
  • 13. Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 611130, China. Electronic address: [email protected].
  • 14. Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 611130, China. Electronic address: [email protected].
  • 15. Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 611130, China. Electronic address: [email protected].
  • 16. Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 611130, China; Sichuan Science-observation Experiment Station for Veterinary Drugs and Veterinary Diagnostic Technology, Ministry of Agriculture, Chengdu, 611130, China; National Animal Experiments Teaching Demonstration Center, Sichuan Agricultural University, Chengdu, 611130, China. Electronic address: [email protected].
  • 17. Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 611130, China; Sichuan Science-observation Experiment Station for Veterinary Drugs and Veterinary Diagnostic Technology, Ministry of Agriculture, Chengdu, 611130, China; National Animal Experiments Teaching Demonstration Center, Sichuan Agricultural University, Chengdu, 611130, China. Electronic address: [email protected].
PMID: 34954542 DOI: 10.1016/j.vetmic.2021.109316
Abstract

Porcine deltacoronavirus (PDCoV) is highly pathogenic to piglets, and no specific drugs or vaccines are available for the prevention and treatment of PDCoV Infection, the need for Antiviral therapies is pressing. HSP90 inhibitors have potent inhibitory effects against the replication of numerous viruses, hence we evaluated three HSP90 inhibitors, 17-AAG, VER-82576, and KW-2478, for their effects on PDCoV Infection in vitro. We evaluated their effectivenesses at suppressing PDCoV by qRT-PCR, western blot, and TCID50 assay, and found that 17-AAG and VER-82576 inhibited PDCoV at the early stage of replication, while KW-2478 showed no significant Antiviral activity at any stage of Infection. These results indicated that the PDCoV-inhibitory effects of 17-AAG and VER-82576 might be exerted by targeting host cell factor HSP90AB1 but not HSP90AA1. Further study showed that HSP90AB1 mRNA and protein levels were not significantly different in 17-AAG and VER-82576-treated cells versus control cells. 17-AAG and VER-82576 were also evaluated for their effects on the expressions of TNF-α, IL-6, and IL-12, which are PDCoV-induced proinflammatory cytokines. We found that both 17-AAG and VER-82576 inhibited the expressions of TNF-α, IL-6, and IL-12 to varying degrees, but in a dose dependent manner. From our data we can conclude that the HSP90 inhibitors 17-AAG and VER-82576 are promising candidates for the treatment of PDCoV Infection.

Keywords
Antiviral effect; HSP90 inhibitors; PDCoV; Proinflammatory cytokines.
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