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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

Pieter H. Anborgh, Igor Kolotilin, Nisha Owens, Abdulla Azzam Mahboob
doi: https://doi.org/10.1101/2021.09.14.460246
Pieter H. Anborgh
1Centre for Applied Research and Innovation in Biotechnology, Fanshawe College, London, Ontario, N5Y 5R6, Canada
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Igor Kolotilin
2Solar Grants Biotechnology Inc., 401-140 Oxford Street E., London, Ontario, N6A 5R9, Canada
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Nisha Owens
1Centre for Applied Research and Innovation in Biotechnology, Fanshawe College, London, Ontario, N5Y 5R6, Canada
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Abdulla Azzam Mahboob
3Department of Chemistry, College of Sciences, United Arab Emirates University, Al-Ain, P.O. Box 15551, United Arab Emirates
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  • For correspondence: abdulla.mahboob@uaeu.ac.ae
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SUMMARY

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 Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted September 14, 2021.
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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
Pieter H. Anborgh, Igor Kolotilin, Nisha Owens, Abdulla Azzam Mahboob
bioRxiv 2021.09.14.460246; doi: https://doi.org/10.1101/2021.09.14.460246
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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
Pieter H. Anborgh, Igor Kolotilin, Nisha Owens, Abdulla Azzam Mahboob
bioRxiv 2021.09.14.460246; doi: https://doi.org/10.1101/2021.09.14.460246

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