11ZW

Structure of the Porcine deltacoronavirus (PDCoV) receptor-binding domain bound to the RBD minibinder 11, the PD3 Fab, and the Kappa light chain nanobody

Summary for 11ZW

• Entry DOI: 10.2210/pdb11zw/pdb
• EMDB information: 76233
• Descriptor: PDCoV IL121_2014 receptor binding domain, RBD minibinder 11, PD3 Fab fragment heavy chain, ... (8 entities in total)
• Functional Keywords: porcine deltacoronavirus, minibinder, protein design, structural genomics, seattle structural genomics center for infectious disease, ssgcid, viral protein
• Biological source: Porcine deltacoronavirus; More
• Total number of polymer chains: 5
• Total formula weight: 112626.68

Authors

Avery, N.G.,Park, Y.J.,Seattle Structural Genomics Center for Infectious Disease (SSGCID),Veesler, D. (deposition date: 2026-03-21, release date: 2026-05-13)

Primary citation

Avery, N.G.,Yoshiyama, C.N.,Taylor, A.L.,Park, Y.J.,Asarnow, D.,Perruzza, L.,Brown, J.T.,Corti, D.,Benigni, F.,Starr, T.N.,Veesler, D.
Computational design of an ultrapotent deltacoronavirus miniprotein inhibitor.
Proc.Natl.Acad.Sci.USA, 123:e2533456123-e2533456123, 2026

PubMed Abstract: Multiple spillovers of porcine deltacoronavirus (PDCoV) into humans in Haiti highlight its zoonotic potential and the need for targeted interventions. No approved vaccines or therapeutics are available for use in humans against any DCoVs. Here, we report the de novo design of PDCoV miniprotein inhibitors (aka minibinders, MBs) and show that one of them, MB11, binds with picomolar affinity to the PDCoV receptor-binding domain (RBD). MB11 potently inhibits PDCoV, outcompeting monoclonal antibodies, and cross-reacts with and broadly neutralizes a panel of distantly related DCoVs. We determined a cryoelectron microscopy structure of MB11 bound to the PDCoV RBD which reveals the molecular basis of broad DCoV neutralization through interference with host receptor engagement. Deep mutational scanning of the PDCoV RBD reveals that MB11 has a high barrier to viral escape with only few mutations mediating escape without dampening APN receptor binding. MB11 resists stringent biochemical stresses, including high temperature, low pH, and proteolysis, which may enable delivery to various tissues for viral inhibition. This work delineates a prime candidate for clinical evaluation against PDCoV infection and for pandemic preparedness.

PubMed: 42054371
DOI: 10.1073/pnas.2533456123

Experimental method

ELECTRON MICROSCOPY (2.8 Å)