An ACE2-blocking antibody confers broad neutralization and protection against Omicron and other SARS-CoV-2 variants

Du, W.; Hurdiss, D. L.; Drabek, D.; Mykytyn, A. Z.; Kaiser, F.; Gonzalez-Hernandez, M.; Munoz-Santos, D.; Lamers, M. M.; van Haperen, R.; Li, W.; Drulyte, I.; Wang, C.; Sola, I.; Armando, F.; Beythien, G.; Ciurkiewicz, M.; Baumgartner, W.; Guilfoyle, K.; Smits, T.; van der Lee, J.; van Kuppeveld, F. J. M.; van Amerongen, G.; Haagmans, B. L.; Enjuanes, L.; Osterhaus, A. D.; Grosveld, F.; Bosch, B. J.

doi:10.1101/2022.02.17.480751

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bioRxiv · 10.1101/2022.02.17.480751

An ACE2-blocking antibody confers broad neutralization and protection against Omicron and other SARS-CoV-2 variants

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Abstract

The ongoing evolution of SARS-CoV-2 has resulted in the emergence of Omicron, which displays striking immune escape potential. Many of its mutations localize to the spike protein ACE2 receptor-binding domain, annulling the neutralizing activity of most therapeutic monoclonal antibodies. Here we describe a receptor-blocking human monoclonal antibody, 87G7, that retains ultrapotent neutralization against SARS-CoV-2 variants including the Alpha, Beta, Gamma, Delta and Omicron (BA.1/BA.2) Variants-of-Concern (VOCs). Structural analysis reveals that 87G7 targets a patch of hydrophobic residues in the ACE2-binding site that are highly conserved in SARS-CoV-2 variants, explaining its broad neutralization capacity. 87G7 protects mice and/or hamsters against challenge with all current SARS-CoV-2 VOCs. Our findings may aid the development of sustainable antibody-based strategies against COVID-19 that are more resilient to SARS-CoV-2 antigenic diversity. One sentence summaryA human monoclonal antibody confers broad neutralization and protection against Omicron and other SARS-CoV-2 variants

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Du, W., Hurdiss, D. L., Drabek, D., Mykytyn, A. Z., Kaiser, F., Gonzalez-Hernandez, M., Munoz-Santos, D., Lamers, M. M., van Haperen, R., Li, W., Drulyte, I., Wang, C., Sola, I., Armando, F., Beythien, G., Ciurkiewicz, M., Baumgartner, W., Guilfoyle, K., Smits, T., van der Lee, J., van Kuppeveld, F. J. M., van Amerongen, G., Haagmans, B. L., Enjuanes, L., Osterhaus, A. D., Grosveld, F., Bosch, B. J.. 2022-02-17. An ACE2-blocking antibody confers broad neutralization and protection against Omicron and other SARS-CoV-2 variants. https://doi.org/10.1101/2022.02.17.480751

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