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 upregulated 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.

中文翻译：

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Ruscogenin 可逆转 SARS-CoV-2 E 蛋白诱导的 THP-1 细胞焦亡。

严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 是一种新出现的致病性冠状病毒，据报道会引起多个细胞和器官的过度炎症和功能障碍，但其潜在机制仍然很大程度上未知。在这里，我们发现外源添加 SARS-CoV-2 包膜蛋白（E 蛋白）可有效诱导培养细胞系（包括 THP-1 单核细胞白血病细胞、内皮细胞和支气管上皮细胞）的细胞死亡，且呈时间和浓度依赖性。方式。SARS-CoV-2 E 蛋白引起 THP-1 中的焦亡样细胞死亡，并导致 GSDMD 裂解。此外，SARS-CoV-2 E 蛋白上调了多种促炎细胞因子的表达，这可能归因于 NF-κB、JNK 和 p38 信号通路的激活。值得注意的是，我们发现了一种天然化合物 Ruscogenin，通过抑制 NLRP3 激活和 GSDMD 裂解，有效逆转 E 蛋白诱导的 THP-1 死亡。总之，这些发现表明 Ruscogenin 可能对预防 SARS-CoV-2 E 蛋白诱导的细胞死亡具有有益作用，并且可能是治疗 COVID-19 并发症的有前途的治疗方法。