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A pan-variant miniprotein inhibitor protects against SARS-CoV-2 variants.

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 pan neutralization of variants that evolved during the 4.5 years since the emergence of SARS-CoV-2 and protects mice against BQ.1.1, XBB.1.5 and BA.2.86 challenge when administered post-exposure by an intranasal route. The resistance of TRI2-2 to viral escape and its direct delivery to the upper airways rationalize a path toward clinical advancement.

SUBMITTER: Lee J

PROVIDER: S-EPMC11326246 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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A pan-variant miniprotein inhibitor protects against SARS-CoV-2 variants.

Lee Jimin J Case James Brett JB Park Young-Jun YJ Ravichandran Rashmi R Asarnow Daniel D Tortorici M Alejandra MA Brown Jack T JT Sanapala Shilpa S Carter Lauren L Baker David D Diamond Michael S MS Veesler David D

bioRxiv : the preprint server for biology 20240810

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 pan neutralization of variants that evolved during ...[more]

PMID: 39149384

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