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  3. SARS-CoV-2 E protein-induced THP-1 pyroptosis is reversed by Ruscogenin

SARS-CoV-2 E protein-induced THP-1 pyroptosis is reversed by Ruscogenin

  • Biochem Cell Biol. 2023 Mar 16. doi: 10.1139/bcb-2022-0359.
Houda Huang 1,  Xiuzhen Li 2,  Duoduo Zha 3,  Hongru Lin 4,  Lingyi Yang 5,  Yihan Wang 6,  Luyan Xu 7,  Linsiqi Wang 8,  Tianhua Lei 9,  Zhou Zhou 10,  Yun-Fei Xiao 11,  Hong-Bo Xin 12,  Mingui Fu 13,  Yisong Qian 14
Affiliations

Affiliations

  • 1 Nanchang University Institute of Translational Medicine, 529927, Nanchang, China; [email protected].
  • 2 Nanchang University Second Affiliated Hospital, 196534, Department of Clinical Laboratory, Nanchang, Jiangxi, China; [email protected].
  • 3 Nanchang University Institute of Translational Medicine, 529927, Nanchang, Jiangxi, China; [email protected].
  • 4 Hainan General Hospital, 26496, Department of Scientific Research, Haikou, Hainan, China; [email protected].
  • 5 Nanchang University Institute of Translational Medicine, 529927, Nanchang, China; [email protected].
  • 6 Nanchang University Institute of Translational Medicine, 529927, Nanchang, China; [email protected].
  • 7 Nanchang University Institute of Translational Medicine, 529927, Nanchang, China; [email protected].
  • 8 Nanchang University Institute of Translational Medicine, 529927, Nanchang, China; [email protected].
  • 9 University of Missouri Kansas City, 12273, Department of Biomedical Sciences, Kansas City, United States; [email protected].
  • 10 University of Missouri Kansas City, 12273, Department of Biomedical Science, Kansas City, United States; [email protected].
  • 11 Nanchang University Institute of Translational Medicine, 529927, Nanchang, China; [email protected].
  • 12 Nanchang University Institute of Translational Medicine, 529927, Nanchang, China; [email protected].
  • 13 University of Missouri Kansas City, 12273, Department of Biomedical Sciences, Kansas City, United States; [email protected].
  • 14 Nanchang University Institute of Translational Medicine, 529927, Nanchang, China; [email protected].
PMID: 36927169 DOI: 10.1139/bcb-2022-0359
Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an emerging pathogenic coronavirus, has been reported to cause excessive inflammation and dysfunction in multiple cells and organs, but the underlying mechanisms remain largely unknown. Here we showed exogenous addition of SARS-CoV-2 envelop protein (E protein) potently induced cell death in cultured cell lines, including THP-1 monocytic leukemia cells, endothelial cells and bronchial epithelial cells, in a time- and concentration-dependent manner. SARS-CoV-2 E protein caused pyroptosis-like cell death in THP-1 and led to GSDMD cleavage. In addition, SARS-CoV-2 E protein up-regulated the expression of multiple pro-inflammatory cytokines that may be attributed to activation of NF-κB, JNK and p38 signal pathways. Notably, we identified a natural compound, Ruscogenin, effectively reversed E protein-induced THP-1 death via inhibition of NLRP3 activation and GSDMD cleavage. In conclusion, these findings suggested that Ruscogenin may have beneficial effects on preventing SARS-CoV-2 E protein-induced cell death and might be a promising treatment for the complications of COVID-19.

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