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| Title | The computationally designed TRI2-2 miniprotein inhibitor protects against multiple SARS-CoV-2 Omicron variants. |
|---|---|
| Journal, issue, pages | Commun Biol, Year 2026 |
| Publish date | Jan 10, 2026 |
Authors | Jimin Lee / James Brett Case / Young-Jun Park / Rashmi Ravichandran / Daniel Asarnow / M Alejandra Tortorici / Jack T Brown / Shilpa Sanapala / Lauren Carter / David Baker / Michael S Diamond / David Veesler / ![]() |
| 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 ...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. |
External links | Commun Biol / PubMed:41519898 |
| Methods | EM (single particle) |
| Resolution | 2.4 - 3.2 Å |
| Structure data | EMDB-45969, PDB-9cwp: EMDB-45971, PDB-9cwq: EMDB-45972, PDB-9cwr: |
| Chemicals | ![]() ChemComp-NAG: ![]() ChemComp-HOH: |
| Source |
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Keywords | VIRAL PROTEIN / Sarbecoviruses / Spike glycoprotein / Structural Genomic / inhibitor / minibinder / Structural Genomics / Seattle Structural Genomics Center for Infectious Disease / SSGCID |
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Sarbecovirus sp.
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