9DF0

PDCoV S RBD bound to PD41 Fab (local refinement)

9DF0 の概要

• エントリーDOI: 10.2210/pdb9df0/pdb
• 関連するPDBエントリー: 9DEZ
• EMDBエントリー: 46804 46805 46806 46814 46815 46816
• 分子名称: Spike glycoprotein, PD41 Fab variable heavy-chain, PD41 Fab variable light-chain, ... (5 entities in total)
• 機能のキーワード: coronavirus, spike, antibody, fab, antigen, pdcov, pd41, complex, viral protein
• 由来する生物種: Porcine deltacoronavirus; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 154366.71

構造登録者

Asarnow, D.,Rexhepaj, M.,Seattle Structural Genomics Center for Infectious Disease (SSGCID),Veesler, D. (登録日: 2024-08-29, 公開日: 2024-11-13, 最終更新日: 2024-12-25)

主引用文献

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

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: 39488210
DOI: 10.1016/j.immuni.2024.10.001

実験手法

ELECTRON MICROSCOPY (2.8 Å)