Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

The SARS-CoV-2 S1 Spike Protein Promotes MAPK and NF-kB Activation and Inflammatory Cytokine Production In Human Lung and Intestinal Epithelial Cells

Christopher B Forsyth
ORCID logo ,
Lijuan Zhang
,
Abhinav Bhushan
ORCID logo ,
Barbara A. Swanson
,
João I. Mamede
ORCID logo ,
Maliha Shaikh
,
Li Zhang
,
Ali Keshavarzian
*
Version 1 : Received: 26 May 2022 / Approved: 1 June 2022 / Online: 1 June 2022 (09:49:27 CEST)

A peer-reviewed article of this Preprint also exists.

Forsyth, C.B.; Zhang, L.; Bhushan, A.; Swanson, B.; Zhang, L.; Mamede, J.I.; Voigt, R.M.; Shaikh, M.; Engen, P.A.; Keshavarzian, A. The SARS-CoV-2 S1 Spike Protein Promotes MAPK and NF-kB Activation in Human Lung Cells and Inflammatory Cytokine Production in Human Lung and Intestinal Epithelial Cells. Microorganisms 2022, 10, 1996. Forsyth, C.B.; Zhang, L.; Bhushan, A.; Swanson, B.; Zhang, L.; Mamede, J.I.; Voigt, R.M.; Shaikh, M.; Engen, P.A.; Keshavarzian, A. The SARS-CoV-2 S1 Spike Protein Promotes MAPK and NF-kB Activation in Human Lung Cells and Inflammatory Cytokine Production in Human Lung and Intestinal Epithelial Cells. Microorganisms 2022, 10, 1996.

Abstract

The Coronavirus disease 2019 (COVID-19) pandemic began in Jan. 2020 in Wuhan, China with a new coronavirus designated SARS-CoV-2. The principle cause of death from COVID-19 disease quickly emerged as Acute Respiratory Distress Syndrome (ARDS). A key ARDS pathogenic mechanism is the “Cytokine Storm”. This is a dramatic increase in the blood of inflammatory cytokines. In the last 2 years of the pandemic new pathology has emerged in COVID-19 survivors in which a variety of long-term symptoms emerge. This condition is called “Long COVID”. The spike protein on the surface of the virus (target for the new mRNA/DNA vaccines) is composed of joined S1-S2 subunits. Upon S1 bind-ing to the human ACE2 receptor on cells, the S1 subunit is cleaved and the S2 subunit me-diates entry of the virus. The S1 protein is then released into the blood, which might be one of the pivotal triggers for initiation and/or perpetuation of the cytokine storm. In this study, we tested the hypothesis that the spike S1 protein may activate inflammatory sig-naling and cytokine production independent of the virus. Our data support a potential role for spike S1 activation of inflammatory signaling and cytokine production in human lung and intestinal epithelial cells in culture. These data support a potential role for the SARS-CoV-2 spike S1 protein in COVID-19 pathogenesis.

Keywords

COVID-19; ARDS; Cytokine Storm; Spike S1 protein; SARS-CoV-2, Long COVID; ACE2; A549 cells; Caco-2 cells

Subject

Medicine and Pharmacology, Pathology and Pathobiology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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