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SARS-CoV-2 Spike Protein Elicits Cell Signaling in Human Host Cells:

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SARS-CoV-2 Spike Protein Elicits Cell Signaling in Human Host Cells: Implications for Possible Consequences of COVID-19 Vaccines

byYuichiro J. Suzuki 1,* and  Sergiy G. Gychka

1. Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, DC 20007, USA

2. Department of Pathological Anatomy N2, Bogomolets National Medical University, 01601 Kiev, Ukraine

*Author to whom correspondence should be addressed.

Vaccines 2021, 9(1), 36; https://doi.org/10.3390/vaccines9010036

Received: 15 December 2020 / Revised: 31 December 2020 / Accepted: 8 January 2021 / Published: 11 January 2021

(This article belongs to the Special Issue SARS-CoV-2 Serological Studies around the Globe)

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Abstract

The world is suffering from the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 uses its spike protein to enter the host cells. Vaccines that introduce the spike protein into our body to elicit virus-neutralizing antibodies are currently being developed. In this article, we note that human host cells sensitively respond to the spike protein to elicit cell signaling. Thus, it is important to be aware that the spike protein produced by the new COVID-19 vaccines may also affect the host cells. We should monitor the long-term consequences of these vaccines carefully, especially when they are administered to otherwise healthy individuals. Further investigations on the effects of the SARS-CoV-2 spike protein on human cells and appropriate experimental animal models are warranted.

Keywords: cell signaling; coronavirus; COVID-19; SARS-CoV-2; spike protein; vaccine

1. Introduction

The world is suffering from the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a positive-sense, single-stranded RNA virus [1,2]. As of the end of December 2020, over 80 million people have been infected with SARS-CoV-2, causing 1.8 million deaths worldwide. SARS-CoV-2 uses its viral membrane fusion protein, known as a spike protein, to bind to angiotensin converting enzyme 2 (ACE2) as a 'receptor' in order to enter human host cells [3,4], causing severe pneumonia and acute respiratory distress syndrome (ARDS) [5]. Elderly patients with cardiovascular disease are particularly susceptible to developing serious COVID-19 conditions that in some cases lead to death, while young and healthy individuals are largely resistant to developing severe symptoms [1,6,7]. As COVID-19 continues to cause serious health, economic, and sociological problems, the world awaits the widespread rollout of effective vaccines that may end this pandemic.

The SARS-CoV-2 spike protein, a class I viral fusion protein, is critical to initiating the interactions between the virus and the host cell surface receptor, facilitating viral entry into the host cell by assisting in the fusion of the viral and host cell membranes. This protein consists of two subunits: Subunit 1 (S1) that contains the ACE2 receptor-binding domain (RBD) and Subunit 2 (S2) that plays a role in the fusion process [3,4] (Figure 1). The SARS-CoV-2 spike protein is the major target for the development of COVID-19 vaccines.

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Figure 1. Structure of SARS-CoV-2 spike protein. The spike protein consists of Subunit 1 (S1) and Subunit 2 (S2). The S1 subunit contains the receptor-binding domain (RBD) that binds to ACE2 of the host cell membrane. The S2 subunit is responsible for fusion. In our previous study described in Section 3 and Section 5, we used full-length S1 (Val16-Gln690) depicted with blue and red regions and the RBD only-containing protein (Arg319-Phe541) shown in red of the SARS-CoV-2 spike protein (GenBank Accession Number: QHD43416.1).

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