A bispecific monomeric nanobody induces SARS-COV-2 spike trimer dimers

Hanke, L.; Das, H.; Sheward, D.; Perez Vidakovics, L.; Urgard, E.; Moliner Morro, A.; Karl, V.; Pankow, A.; Changil, K.; Smith, N.; Pedersen, G.; Coquet, J. M.; Hallberg, B. M.; Murrell, B.; McInerney, G. M.

doi:10.1101/2021.03.20.436243

bioRxiv · 10.1101/2021.03.20.436243

A bispecific monomeric nanobody induces SARS-COV-2 spike trimer dimers

Hanke, L.·Das, H.·Sheward, D.·Perez Vidakovics, L.·Urgard, E.·Moliner Morro, A.·Karl, V.·Pankow, A.·Changil, K.·Smith, N.·Pedersen, G.·Coquet, J. M.·Hallberg, B. M.·Murrell, B.·McInerney, G. M.

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Abstract

Antibodies binding to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike have therapeutic promise, but emerging variants show the potential for virus escape. This emphasizes the need for therapeutic molecules with distinct and novel neutralization mechanisms. Here we isolated a nanobody that interacts simultaneously with two RBDs from different spike trimers of SARS-CoV-2, rapidly inducing the formation of spike trimer-dimers leading to the loss of their ability to attach to the host cell receptor, ACE2. We show that this nanobody potently neutralizes SARS-CoV-2, including the B.1.351 variant, and cross-neutralizes SARS-CoV. Furthermore, we demonstrate the therapeutic potential of the nanobody against SARS-CoV-2 and the B.1.351 variant in a human ACE2 transgenic mouse model. This naturally elicited bispecific monomeric nanobody establishes a novel strategy for potent inactivation of viral antigens and represents a promising antiviral against emerging SARS-CoV-2 variants.

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Hanke, L., Das, H., Sheward, D., Perez Vidakovics, L., Urgard, E., Moliner Morro, A., Karl, V., Pankow, A., Changil, K., Smith, N., Pedersen, G., Coquet, J. M., Hallberg, B. M., Murrell, B., McInerney, G. M.. 2021-03-21. A bispecific monomeric nanobody induces SARS-COV-2 spike trimer dimers. https://doi.org/10.1101/2021.03.20.436243

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