Development of efficient therapies for COVID-19 is the focus of intense research. The cytokine release syndrome was underlined as a culprit for severe outcomes in COVID-19 patients. Interleukin-6 (IL-6) plays a crucial role in human immune responses and elevated IL-6 plasma levels have been associated with the exacerbated COVID-19 pathology. Since non-structural protein 10 (NSP10) of SARS-CoV-2 has been implicated in the induction of IL-6, we designed Peptide (P)1, containing sequences corresponding to amino acids 68-96 of NSP10, and examined its effect on cultured human cells. Treatment with P1 strongly increased IL-6 secretion by the lung cancer cell line NCI-H1792 and the breast cancer cell line MDA-MB-231 and revealed profound cytotoxic activity on Caco-2 colorectal adenocarcinoma cells. Treatment with P2, harbouring a mutation in the zinc knuckle motif of NSP10, caused no IL-6 induction and no cytotoxicity. Pre-treatment with plant-produced human anti-inflammatory cytokines IL-37b and IL-38 effectively mitigated the induction of IL-6 secretion. Our results suggest a role for the zinc knuckle motif of NSP10 in the onset of increased IL-6 plasma levels of COVID-19 patients and for IL-37b and IL-38 as therapeutics aimed at attenuating the cytokine release syndrome.

中文翻译：

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SARS-CoV-2 衍生肽对人体细胞中 IL-6 的多产诱导被植物中制造的重组人抗炎细胞因子减弱

开发有效的 COVID-19 疗法是深入研究的重点。细胞因子释放综合征被强调为 COVID-19 患者出现严重后果的罪魁祸首。白细胞介素 6 (IL-6) 在人类免疫反应中起着至关重要的作用，并且升高的 IL-6 血浆水平与加重的 COVID-19 病理有关。由于 SARS-CoV-2 的非结构蛋白 10 (NSP10) 与 IL-6 的诱导有关，我们设计了肽 (P)1，包含对应于 NSP10 的氨基酸 68-96 的序列，并检查其作用在培养的人体细胞上。用 P1 处理强烈增加肺癌细胞系 NCI-H1792 和乳腺癌细胞系 MDA-MB-231 的 IL-6 分泌，并显示出对 Caco-2 结肠直肠腺癌细胞的深刻细胞毒活性。用P2处理，在 NSP10 的锌指节基序中含有突变，不会引起 IL-6 诱导和细胞毒性。用植物产生的人类抗炎细胞因子 IL-37b 和 IL-38 进行预处理可有效减轻 IL-6 分泌的诱导。我们的结果表明 NSP10 的锌指节基序在 COVID-19 患者血浆 IL-6 水平升高中的作用，以及作为旨在减轻细胞因子释放综合征的治疗剂的 IL-37b 和 IL-38。