PT  - JOURNAL ARTICLE
AU  - Yuichiro J. Suzuki
AU  - Sofia I. Nikolaienko
AU  - Vyacheslav A. Dibrova
AU  - Yulia V. Dibrova
AU  - Volodymyr M. Vasylyk
AU  - Mykhailo Y. Novikov
AU  - Nataliia V. Shults
AU  - Sergiy G. Gychka
TI  - SARS-CoV-2 spike protein-mediated cell signaling in lung vascular cells
AID  - 10.1101/2020.10.12.335083
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.10.12.335083
4099  - http://biorxiv.org/content/early/2020/10/12/2020.10.12.335083.short
4100  - http://biorxiv.org/content/early/2020/10/12/2020.10.12.335083.full
AB  - Currently, the world is suffering from the pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that uses angiotensin-converting enzyme 2 (ACE2) as a receptor to enter the host cells. So far, 30 million people have been infected with SARS-CoV-2, and nearly 1 million people have died because of COVID-19 worldwide, causing serious health, economical, and sociological problems. However, the mechanism of the effect of SARS-CoV-2 on human host cells has not been defined. The present study reports that the SARS-CoV-2 spike protein alone without the rest of the viral components is sufficient to elicit cell signaling in lung vascular cells. The treatment of human pulmonary artery smooth muscle cells or human pulmonary artery endothelial cells with recombinant SARS-CoV-2 spike protein S1 subunit (Val16 – Gln690) at 10 ng/ml (0.13 nM) caused an activation of MEK phosphorylation. The activation kinetics was transient with a peak at 10 min. The recombinant protein that contains only the ACE2 receptor-binding domain of SARS-CoV-2 spike protein S1 subunit (Arg319 – Phe541), on the other hand, did not cause this activation. Consistent with the activation of cell growth signaling in lung vascular cells by SARS-CoV-2 spike protein, pulmonary vascular walls were found to be thickened in COVID-19 patients. Thus, SARS-CoV-2 spike protein-mediated cell growth signaling may participate in adverse cardiovascular/pulmonary outcomes, and this mechanism may provide new therapeutic targets to combat COVID-19.Competing Interest StatementThe authors have declared no competing interest.AbbreviationsACE2angiotensin-converting enzyme 2;ARDSacute respiratory distress syndrome;COVID-19coronavirus disease 2019;RBDreceptor-binding domain;SARS-CoV-2severe acute respiratory syndrome coronavirus 2