PT  - JOURNAL ARTICLE
AU  - Anborgh, Pieter H.
AU  - Kolotilin, Igor
AU  - Owens, Nisha
AU  - Mahboob, Abdulla Azzam
TI  - Prolific Induction of IL-6 in Human Cells by SARS-CoV-2-derived Peptide is Attenuated by Recombinant Human Anti-inflammatory Cytokines made <em>in planta</em>
AID  - 10.1101/2021.09.14.460246
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.09.14.460246
4099  - http://biorxiv.org/content/early/2021/09/14/2021.09.14.460246.short
4100  - http://biorxiv.org/content/early/2021/09/14/2021.09.14.460246.full
AB  - 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.