9CWR

SARS-CoV-2 BA.2.86 Spike trimer in complex with TRI2-2 minibinder

Summary for 9CWR

• Entry DOI: 10.2210/pdb9cwr/pdb
• Related: 9CWP 9CWQ
• EMDB information: 45969 45971 45972
• Descriptor: BA.2.86 spike protein, TRI2-2 minibinder, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: sarbecoviruses, spike glycoprotein, structural genomic, inhibitor, viral protein, minibinder, structural genomics, seattle structural genomics center for infectious disease, ssgcid
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2); More
• Total number of polymer chains: 6
• Total formula weight: 491021.57

Authors

Lee, J.,Veesler, D.,Seattle Structural Genomics Center for Infectious Disease (SSGCID) (deposition date: 2024-07-30, release date: 2026-01-21)

Primary citation

Lee, J.,Case, J.B.,Park, Y.J.,Ravichandran, R.,Asarnow, D.,Tortorici, M.A.,Brown, J.T.,Sanapala, S.,Carter, L.,Baker, D.,Diamond, M.S.,Veesler, D.
The computationally designed TRI2-2 miniprotein inhibitor protects against multiple SARS-CoV-2 Omicron variants.
Commun Biol, 2026

PubMed Abstract: The continued evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has compromised neutralizing antibody responses elicited by prior infection or vaccination and abolished the utility of most monoclonal antibody therapeutics. We previously described a computationally-designed, homotrimeric miniprotein inhibitor, designated TRI2-2, that protects mice against pre-Omicron SARS-CoV-2 variants. Here, we show that TRI2-2 exhibits broadly neutralizing activity of SARS-CoV-2 variants and protects mice against BQ.1.1, XBB.1.5 and BA.2.86 challenge when administered intranasally post-exposure. The resistance of TRI2-2 to viral escape by most variants and the ability to deliver it directly to the upper airways highlight the potential of the multivalent miniprotein inhibitor as an alternative therapeutic modality.

PubMed: 41519898
DOI: 10.1038/s42003-025-09499-2

Experimental method

ELECTRON MICROSCOPY (2.4 Å)