How to combat (and understand) SARS-CoV-2 with Camelid Nanobodies | New Voices in Infection Biology

  • Date: May 5, 2021
  • Time: 16:00
  • Speaker: Florian I. Schmidt
  • University of Bonn
  • Location: Zoom video conference
  • Host: Olivia Majer
  • Contact: vseminars@mpiib-berlin.mpg.de
How to combat (and understand) SARS-CoV-2 with Camelid Nanobodies | New Voices in Infection Biology

If you are interested in joining the seminar, please contact: vseminars@mpiib-berlin.mpg.de

Once registered, you will receive a zoom conference link 30 mins before the talk starts - please sign in using your full name.

Talk abstract:

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 non-infectious.

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