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

Lee, J.; Case, J. B.; Ravichandran, R.; Asarnow, D.; Tortorici, M. A.; Brown, J. T.; Sanapala, S.; Carter, L.; Baker, D.; Diamond, M. S.; Veesler, D.

doi:10.1101/2024.08.08.606885

bioRxiv · 10.1101/2024.08.08.606885

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

Lee, J.·Case, J. B.·Ravichandran, R.·Asarnow, D.·Tortorici, M. A.·Brown, J. T.·Sanapala, S.·Carter, L.·Baker, D.·Diamond, M. S.·Veesler, D.

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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.

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Lee, J., Case, J. B., Ravichandran, R., Asarnow, D., Tortorici, M. A., Brown, J. T., Sanapala, S., Carter, L., Baker, D., Diamond, M. S., Veesler, D.. 2024-08-10. A pan-variant miniprotein inhibitor protects against SARS-CoV-2 variants. https://doi.org/10.1101/2024.08.08.606885

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