Stabilized Coronavirus Spike Glycoproteins in the Pre-Fusion Conformation


Coronavirus uses the spike (S) protein to gain entry into host cells. The S protein binds to host cell receptors, leading to a series of conformational changes that convert the pre-fusion S structure into the post-fusion S structure, pulling the viral and host membranes together. Current COVID‑19 vaccines work by exposing the host to the viral S protein. Unmodified S proteins tend to be unstable and readily transition to the post‑fusion state. Since the antibodies need to bind to the pre‑fusion structure to improve immune response, stabilizing the spike in the pre‑fusion structure has been a large focus among COVID‑19 vaccine research. Stabilizing the S protein in the pre‑fusion conformation involves rigidification of the S protein central helix, which changes interactions between the central helix and the receptor binding domain. The change to these interactions has been reported to change the spike flexibility and motion of the receptor binding domain as compared to the true coronavirus spike. Many known antibodies bind to the receptor binding domain, and thus maintaining the original flexibility is expected to be important.


Researchers at Stony Brook University (SBU) propose stabilizing the pre‑fusion spike glycoprotein by introducing a specifically designed disulfide bond that “staples” together the S central helix and its Heptad Repeat 1 (HR1) domain. By preventing HR1 from detaching from CH, the prefusion spike structure can be stabilized without rigidification of the central helix or changes to its interaction with the receptor binding domain. This disulfide-stapled spike allows for a stable vaccine without the need for the stabilizing mutations that are currently in use.



Coronavirus vaccines

Patent Status

Provisional patent

Stage Of Development


Licensing Potential

Development partner - Commercial partner - Licensing

Licensing Status


Additional Info

Additional Information: dottedyeti,,
Patent Information:
Case ID: R050-9315
For Information, Contact:
Valery Matthys
Licensing Associate
State University of New York at Stony Brook
Carlos Simmerling