SARS-CoV-2 spike protein-mediated cell signaling in lung vascular cells

Yuichiro J Suzuki,Sofia I Nikolaienko,Vyacheslav A Dibrova,Yulia V Dibrova,Volodymyr M Vasylyk,Mykhailo Y Novikov,Nataliia V Shults,Sergiy G Gychka

doi:10.1016/j.vph.2020.106823

Abstract

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, 60 million people have been infected with SARS-CoV-2, and 1.4 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 the 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 the 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.

Highlights

Coronaviruses are positive sense single stranded RNA viruses that often cause the common cold [1,2]
The kinetics of MEK phosphorylation promoted by the full-length Subunit 1 (S1) subunit (Val16 - Gln690) of the SARS-CoV-2 spike protein was consistently found to be transient with a peak at 10 min
The major finding of this study is that the SARS-CoV-2 spike protein without the rest of the virus can elicit cell signaling, the activation of the MEK/extracellular-regulated kinase (ERK) pathway, in human host lung vascular smooth muscle and endothelial cells

Summary

Introduction

Coronaviruses are positive sense single stranded RNA viruses that often cause the common cold [1,2]. The world is suffering from the pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [3,4]. 30 million people have been infected with SARS-CoV-2 worldwide, causing serious health, economical, and sociological problems. SARS-CoV-2 uses angiotensin converting enzyme 2 (ACE2) as a receptor to enter the host cells [5,6]. Lung cells are the primary targets of SARS-CoV-2, resulting in severe pneumonia and acute respiratory distress syndrome (ARDS) [7,8]. Nearly 1 million people have died because of COVID-19

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Discussion

Conclusion