SARS-CoV-2 Spike S1 Products

The SARS-CoV-2 Spike protein is one of the four major structural proteins of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19 (1,2). The spike protein is the largest of the structural proteins, which also include the membrane (M), envelope (E), and nucleocapsid (N) proteins (1,2). The SARS-CoV-2 spike protein is a 1273 amino acid (aa) heterotrimeric class I fusion protein with each monomer having a theoretical molecular weight of approximately 180 kDa (1). The club-shaped spike protein contains several functional regions and domains including the S1 globular head region which contains the N-terminal receptor-binding domain (RBD) and the S2 stem region that contains the C-terminal fusion domain, two heptad regions, a transmembrane domain, and a cytoplasmic tail (1,2). The viral spike protein is critical for attachment of the virus with the host cell, resulting in fusion and virus entry into the cell (1,2). More specifically, the RBD of the spike protein is responsible for binding to the cell surface receptor angiotensin converting enzyme 2 (ACE2) (1,2). This spike-ACE2 interaction results in a conformational change permitting furin cleavage between the S1 and S2 domains and then cleavage at S2' by TMPRRS2, or another protease, allowing membrane fusion (1,2).

Given the critical role of the spike protein RBD in the interaction with the ACE2 receptor and viral entry, a number of neutralizing antibodies against the RBD have been developed as potential therapeutics for treating COVID-19 (3). These antibodies bind the RBD domain on the S1 subunit inhibiting the interaction with ACE2 (3). However, more studies need to be done as neutralizing antibodies can result in antibody-dependent enhancement, in which the viral entry and replication within the host cell is increased (4). One potential way to combat antibody-dependent enhancement is the use of nanobodies (4). Furthermore, there are currently several vaccine strategies that are in clinical trials, or recently federally approved, that utilize the spike protein in different forms (e.g. full length, S1 RBD, RBD-Fc, N-terminal) for protecting against SARS-CoV-2 infection (4,5). These vaccine strategies include DNA vaccines, viral vector-based vaccines, RNA vaccines, and subunit vaccines (4,5).

References

1. Pillay T. S. (2020). Gene of the month: the 2019-nCoV/SARS-CoV-2 novel coronavirus spike protein. Journal of Clinical Pathology. https://doi.org/10.1136/jclinpath-2020-206658

2. Malik Y. A. (2020). Properties of Coronavirus and SARS-CoV-2. The Malaysian Journal of Pathology.

3. Ho M. (2020). Perspectives on the development of neutralizing antibodies against SARS-CoV-2. Antibody Therapeutics. https://doi.org/10.1093/abt/tbaa009

4. Samrat, S. K., Tharappel, A. M., Li, Z., & Li, H. (2020). Prospect of SARS-CoV-2 spike protein: Potential role in vaccine and therapeutic development. Virus Research. https://doi.org/10.1016/j.virusres.2020.198141

5. Sternberg, A., & Naujokat, C. (2020). Structural features of coronavirus SARS-CoV-2 spike protein: Targets for vaccination. Life Sciences. https://doi.org/10.1016/j.lfs.2020.118056