Implications for SARS-CoV-2 Vaccine Design: Fusion of Spike Glycoprotein Transmembrane Domain to Receptor-Binding Domain Induces Trimerization

Taha Azad; Ragunath Singaravelu; Mathieu J F Crupi; Taylor Jamieson; Jaahnavi Dave; Emily E F Brown; Reza Rezaei; Zaid Taha; Stephen Boulton; Nikolas T Martin; Abera Surendran; Joanna Poutou; Mina Ghahremani; Kazem Nouri; Jack T Whelan; Jessie Duong; Sarah Tucker; Jean-Simon Diallo; John C Bell; Carolina S Ilkow

doi:10.3390/membranes10090215

Implications for SARS-CoV-2 Vaccine Design: Fusion of Spike Glycoprotein Transmembrane Domain to Receptor-Binding Domain Induces Trimerization

Membranes (Basel). 2020 Aug 30;10(9):215. doi: 10.3390/membranes10090215.

Authors

Taha Azad^{1

2}, Ragunath Singaravelu^{1

2}, Mathieu J F Crupi^{1

2}, Taylor Jamieson^{1

2}, Jaahnavi Dave^{1

2}, Emily E F Brown^{1

2}, Reza Rezaei^{1

2}, Zaid Taha^{1

2}, Stephen Boulton^{1

2}, Nikolas T Martin^{1

2}, Abera Surendran^{1

2}, Joanna Poutou^{1

2}, Mina Ghahremani³, Kazem Nouri⁴, Jack T Whelan^{1

2}, Jessie Duong^{1

2}, Sarah Tucker^{1

2}, Jean-Simon Diallo^{1

2}, John C Bell^{1

2}, Carolina S Ilkow^{1

2}

Affiliations

¹ Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.
² Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
³ Department of Biology, University of Ottawa, Ottawa, ON K1N 6N5, Canada.
⁴ Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2C1, Canada.

Abstract

The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic presents an urgent need for an effective vaccine. Molecular characterization of SARS-CoV-2 is critical to the development of effective vaccine and therapeutic strategies. In the present study, we show that the fusion of the SARS-CoV-2 spike protein receptor-binding domain to its transmembrane domain is sufficient to mediate trimerization. Our findings may have implications for vaccine development and therapeutic drug design strategies targeting spike trimerization. As global efforts for developing SARS-CoV-2 vaccines are rapidly underway, we believe this observation is an important consideration for identifying crucial epitopes of SARS-CoV-2.

Keywords: SARS-CoV-2; receptor-binding domain; spike protein; transmembrane domain; trimerization; vaccine development.

Grants and funding

448323/CAPMC/ CIHR/Canada