EMD-26512

Single-particle
3.1 Å
EMD-26512 Deposition: 26/03/2022
Map released: 08/06/2022
Last modified: 30/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-26512

SARS-CoV-2 spike in complex with AHB2-2GS-SB175

EMD-26512

Single-particle
3.1 Å
EMD-26512 Deposition: 26/03/2022
Map released: 08/06/2022
Last modified: 30/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Severe acute respiratory syndrome coronavirus 2, synthetic construct
Sample: SARS-CoV-2 spike in complex with multivalent minibinder AHB2-2GS-SB175
Fitted models: 7uhc (Avg. Q-score: 0.465)

Deposition Authors: Park YJ , Seattle Structural Genomics Center for Infectious Disease (SSGCID), Veesler D
Multivalent designed proteins neutralize SARS-CoV-2 variants of concern and confer protection against infection in mice.
PUBMED: 35412328
DOI: doi:10.1126/scitranslmed.abn1252
ISSN: 1946-6242
Abstract:
New variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to arise and prolong the coronavirus disease 2019 (COVID-19) pandemic. Here, we used a cell-free expression workflow to rapidly screen and optimize constructs containing multiple computationally designed miniprotein inhibitors of SARS-CoV-2. We found the broadest efficacy was achieved with a homotrimeric version of the 75-residue angiotensin-converting enzyme 2 (ACE2) mimic AHB2 (TRI2-2) designed to geometrically match the trimeric spike architecture. Consistent with the design model, in the cryo-electron microscopy structure TRI2-2 forms a tripod at the apex of the spike protein that engaged all three receptor binding domains simultaneously. TRI2-2 neutralized Omicron (B.1.1.529), Delta (B.1.617.2), and all other variants tested with greater potency than the monoclonal antibodies used clinically for the treatment of COVID-19. TRI2-2 also conferred prophylactic and therapeutic protection against SARS-CoV-2 challenge when administered intranasally in mice. Designed miniprotein receptor mimics geometrically arrayed to match pathogen receptor binding sites could be a widely applicable antiviral therapeutic strategy with advantages over antibodies in greater resistance to viral escape and antigenic drift, and advantages over native receptor traps in lower chances of autoimmune responses.