@article {Anborgh2021.09.14.460246, author = {Pieter H. Anborgh and Igor Kolotilin and Nisha Owens and Abdulla Azzam Mahboob}, title = {Prolific Induction of IL-6 in Human Cells by SARS-CoV-2-derived Peptide is Attenuated by Recombinant Human Anti-inflammatory Cytokines made in planta}, elocation-id = {2021.09.14.460246}, year = {2021}, doi = {10.1101/2021.09.14.460246}, publisher = {Cold Spring Harbor Laboratory}, abstract = {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.Competing Interest StatementThe authors have declared no competing interest.}, URL = {https://www.biorxiv.org/content/early/2021/09/14/2021.09.14.460246}, eprint = {https://www.biorxiv.org/content/early/2021/09/14/2021.09.14.460246.full.pdf}, journal = {bioRxiv} }