The computationally designed TRI2-2 miniprotein inhibitor protects against multiple SARS-CoV-2 Omicron variants

Communications Biology 2026 Open access

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Authors: Jimin Lee, James Brett Case, Young‐Jun Park, Rashmi Ravichandran, Daniel Asarnow, M. Alejandra Tortorici, Jack Brown, Shilpa Sanapala, Lauren Carter, D Baker, Michael S. Diamond, David Veesler
DOI: 10.1038/s42003-025-09499-2
Cited by: 2
References: 44

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.

Fields of Study & Subjects

SARS-CoV-2 and COVID-19 Research interferon and immune responses vaccines and immunoinformatics approaches

Publication details

Journal / source
Communications Biology
Publisher
Springer Science and Business Media LLC
Volume
9
Issue
1
Pages
224–224
Publication date
10 January 2026
Language
EN