How to combat (and understand) SARS-CoV-2 with Camelid Nanobodies | New Voices in Infection Biology
- Datum: 05.05.2021
- Uhrzeit: 16:00
- Vortragende(r): Florian I. Schmidt
- University of Bonn
- Ort: Zoom video conference
- Gastgeber: Olivia Majer
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The severe acute respiratory-syndrome coronavirus 2
(SARS-CoV-2) pandemic continues to spread with devastating consequences. For
passive immunization efforts, nanobodies have size and cost advantages over
conventional antibodies. Here, we generated four neutralizing nanobodies that target
the receptor-binding domain of the SARS-CoV-2 spike protein. We defined two
distinct binding epitopes using X-ray crystallography and cryo-electron
microscopy. Based on the structures, we engineered multivalent nanobodies with
more than 100-fold improved neutralizing activity than monovalent nanobodies.
Biparatopic nanobody fusions suppressed the emergence of escape mutants.
Several nanobody constructs neutralized through receptor-binding competition,
while other monovalent and biparatopic nanobodies triggered aberrant activation
of the spike fusion machinery. These premature conformational changes in the
spike protein forestalled productive fusion, and rendered the virions