Figure: Cryo-EM structure of the most abundant trimer class of S-closed-Fd-a closed S protein trimer on the left (PDB accession code: 7A4N) and the less representative open trimer class on the right (PDB accession code: 7AD1). Colored by local resolution cyan being the highest resolution and purple the lowest.
A team from Janssen Vaccines & Prevention B.V collaborated with the Netherlands Center for Electron Nanoscopy (NeCEN), part of Instruct Centre NL, to create and characterise new stable variants of the S trimer, one of the main targets for SARS-CoV-2 vaccine development.
The S trimer is a large viral surface protein crucial for the viral life cycle that mediates both the interaction and the fusion of the SARS-CoV-2 virus with host cells, however its instability makes the isolation of stable S-closed proteins in a pre-fusion state challenging. The study developed a stable S protein, by producing new variants from single mutations. A stable variant was identified, then confirmed using cryo-EM that it retained the pre-fusion conformation – which could then be used in the advanced development of vaccines.
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