Characterisation of a novel ACE2-based therapeutic with enhanced rather than reduced activity against SARS-CoV2 variants

Ferrari, M.; Mekkaoui, L.; Ilca, F. T.; Akbar, Z.; Bughda, R.; Lamb, K.; Ward, K.; Parekh, F.; Karattil, R.; Allen, C.; Wu, P.; Baldan, V.; Mattiuzzo, G.; Bentley, E. M.; Takeuchi, Y.; Sillibourne, J.; Datta, P.; Kinna, A.; Pule, M.; Onuoha, S.

doi:10.1101/2021.03.17.435802

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bioRxiv · 10.1101/2021.03.17.435802

Characterisation of a novel ACE2-based therapeutic with enhanced rather than reduced activity against SARS-CoV2 variants

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Abstract

The human angiotensin-converting enzyme 2 acts as the host cell receptor for SARS-CoV-2 and the other members of the Coronaviridae family SARS-CoV-1 and HCoV-NL63. Here we report the biophysical properties of the SARS-CoV-2 spike variants D614G, B.1.1.7 and B.1.351 with affinities to the ACE2 receptor and infectivity capacity, revealing weaknesses in the developed neutralising antibody approaches. Furthermore, we report a pre-clinical characterisation package for a soluble receptor decoy engineered to be catalytically inactive and immunologically inert, with broad neutralisation capacity, that represents an attractive therapeutic alternative in light of the mutational landscape of COVID-19. This construct efficiently neutralised four SARS-CoV-2 variants of concern. The decoy also displays antibody-like biophysical properties and manufacturability, strengthening its suitability as a first-line treatment option in prophylaxis or therapeutic regimens for COVID-19 and related viral infections.

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Ferrari, M., Mekkaoui, L., Ilca, F. T., Akbar, Z., Bughda, R., Lamb, K., Ward, K., Parekh, F., Karattil, R., Allen, C., Wu, P., Baldan, V., Mattiuzzo, G., Bentley, E. M., Takeuchi, Y., Sillibourne, J., Datta, P., Kinna, A., Pule, M., Onuoha, S.. 2021-03-17. Characterisation of a novel ACE2-based therapeutic with enhanced rather than reduced activity against SARS-CoV2 variants. https://doi.org/10.1101/2021.03.17.435802

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