7RBY

Crystal structure of Nanobody nb112 and SARS-CoV-2 RBD

Summary for 7RBY

• Entry DOI: 10.2210/pdb7rby/pdb
• Descriptor: Spike protein S1, Ilama-isolated nanobody NIH-CoV nb-112 specific to SARS-CoV-2 RBD, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: sars-cov-2, nanobody, rbd-specific, broad neutralization, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 4
• Total formula weight: 75756.73

Authors

Chen, Y.,Tolbert, W.,Pazgier, M. (deposition date: 2021-07-06, release date: 2022-03-23, Last modification date: 2024-10-23)

Primary citation

Esparza, T.J.,Chen, Y.,Martin, N.P.,Bielefeldt-Ohmann, H.,Bowen, R.A.,Tolbert, W.D.,Pazgier, M.,Brody, D.L.
Nebulized delivery of a broadly neutralizing SARS-CoV-2 RBD-specific nanobody prevents clinical, virological, and pathological disease in a Syrian hamster model of COVID-19.
Mabs, 14:2047144-2047144,

PubMed Abstract: There remains an unmet need for globally deployable, low-cost therapeutics for the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Previously, we reported on the isolation and characterization of a potent single-domain nanobody, NIH-CoVnb-112, specific for the receptor-binding domain (RBD) of SARS-CoV-2. Here, we report on the molecular basis for the observed broad neutralization capability of NIH-CoVnb-112 against variant SARS-CoV-2 pseudoviruses. The structure of NIH-CoVnb-112 bound to SARS-CoV-2 RBD reveals a large contact surface area overlapping the angiotensin converting enzyme 2 (ACE2) binding site, which is largely unencumbered by the common RBD mutations. In an pilot study, we demonstrate effective reductions in weight loss, viral burden, and lung pathology in a Syrian hamster model of COVID-19 following nebulized delivery of NIH-CoVnb-112. These findings support the further development of NIH-CoVnb-112 as a potential adjunct preventative therapeutic for the treatment of SARS-CoV-2 infection. ACE2 - angiotensin converting enzyme 2BSA - buried surface areaCDR - complementary determining regionRBD - receptor binding domainRBM - receptor-binding motifSARS-CoV-2 - severe acute respiratory syndrome coronavirus 2.

PubMed: 35289719
DOI: 10.1080/19420862.2022.2047144

Experimental method

X-RAY DIFFRACTION (2.82 Å)