9YYV
SARS-CoV-2 spike trimer in the early fusion intermediate conformation bound to the VN01H1 Fab (S2 local refinement)
Summary for 9YYV
| Entry DOI | 10.2210/pdb9yyv/pdb |
| EMDB information | 73657 |
| Descriptor | Spike glycoprotein, 2-acetamido-2-deoxy-beta-D-glucopyranose (2 entities in total) |
| Functional Keywords | virus, coronaviruses, e-fic, ace2, glycoprotein, receptor, structural genomics, seattle structural genomics center for infectious disease, ssgcid, viral protein |
| Biological source | Severe acute respiratory syndrome coronavirus 2 |
| Total number of polymer chains | 3 |
| Total formula weight | 428145.07 |
| Authors | Park, Y.J.,Seattle Structural Genomics Center for Infectious Disease (SSGCID),Veesler, D. (deposition date: 2025-10-29, release date: 2026-05-13) |
| Primary citation | McCallum, M.,Case, J.B.,Brown, J.T.,Park, Y.J.,Lee, J.,Sutherland, E.,Aggarwal, A.,Gibson, C.,Lempp, F.A.,Stewart, C.,Tortorici, M.A.,Sanapala, S.,Low, J.S.,Asarnow, D.,Bohan, D.,Dellota Jr., E.,Merz, B.,Chawla, B.,Kar, S.,Lanzavecchia, A.,Sallusto, F.,Riley, N.M.,Turville, S.,Purcell, L.,Diamond, M.S.,Veesler, D. TMPRSS2-mediated coronavirus spike activation and inhibition. Nat.Struct.Mol.Biol., 2026 Cited by PubMed Abstract: The protease TMPRSS2 facilitates coronavirus infections, yet its mechanism of viral glycoprotein recognition remains unclear. Here we show that, following ACE2 engagement of the SARS-CoV-2 spike (S) inducing the early fusion intermediate conformation (E-FIC), TMPRSS2 cleaves the R815 S' site and promotes fusogenic conformational changes leading to viral entry. We unveil TMPRSS2 recognition of S', identify key residues modulating binding specificity and demonstrate that S' site-directed broadly neutralizing antibodies target E-FIC and inhibit viral entry by blocking TMPRSS2 access. We computationally designed stabilized E-FIC as a vaccine candidate, overcoming the transient nature of this state. We describe a TMPRSS2-directed monoclonal antibody inhibiting several coronaviruses, including SARS-CoV-2 variants and protecting mice against SARS-CoV-2 challenge. These results outline the mechanistic role of TMPRSS2 and S' site-directed antibodies in coronavirus entry. PubMed: 42050172DOI: 10.1038/s41594-026-01801-y PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.3 Å) |
Structure validation
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