9DF0
PDCoV S RBD bound to PD41 Fab (local refinement)
Summary for 9DF0
| Entry DOI | 10.2210/pdb9df0/pdb |
| Related | 9DEZ |
| EMDB information | 46804 46805 46806 46814 46815 46816 |
| Descriptor | Spike glycoprotein, PD41 Fab variable heavy-chain, PD41 Fab variable light-chain, ... (5 entities in total) |
| Functional Keywords | coronavirus, spike, antibody, fab, antigen, pdcov, pd41, complex, viral protein |
| Biological source | Porcine deltacoronavirus More |
| Total number of polymer chains | 3 |
| Total formula weight | 154366.71 |
| Authors | Asarnow, D.,Rexhepaj, M.,Seattle Structural Genomics Center for Infectious Disease (SSGCID),Veesler, D. (deposition date: 2024-08-29, release date: 2024-11-13, Last modification date: 2024-12-25) |
| Primary citation | Rexhepaj, M.,Asarnow, D.,Perruzza, L.,Park, Y.J.,Guarino, B.,Mccallum, M.,Culap, K.,Saliba, C.,Leoni, G.,Balmelli, A.,Yoshiyama, C.N.,Dickinson, M.S.,Quispe, J.,Brown, J.T.,Tortorici, M.A.,Sprouse, K.R.,Taylor, A.L.,Corti, D.,Starr, T.N.,Benigni, F.,Veesler, D. Isolation and escape mapping of broadly neutralizing antibodies against emerging delta-coronaviruses. Immunity, 57:2914-, 2024 Cited by PubMed Abstract: Porcine delta-coronavirus (PDCoV) spillovers were recently detected in febrile children, underscoring the recurrent zoonoses of divergent CoVs. To date, no vaccines or specific therapeutics are approved for use in humans against PDCoV. To prepare for possible future PDCoV epidemics, we isolated PDCoV spike (S)-directed monoclonal antibodies (mAbs) from humanized mice and found that two, designated PD33 and PD41, broadly neutralized a panel of PDCoV variants. Cryoelectron microscopy (cryo-EM) structures of PD33 and PD41 in complex with the S receptor-binding domain (RBD) and ectodomain trimer revealed the epitopes recognized by these mAbs, rationalizing their broad inhibitory activity. We show that both mAbs competitively interfere with host aminopeptidase N binding to neutralize PDCoV and used deep-mutational scanning epitope mapping to associate RBD antigenic sites with mAb-mediated neutralization potency. Our results indicate a PD33-PD41 mAb cocktail may heighten the barrier to escape. PD33 and PD41 are candidates for clinical advancement against future PDCoV outbreaks. PubMed: 39488210DOI: 10.1016/j.immuni.2024.10.001 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.8 Å) |
Structure validation
Download full validation report
