Speaker
Description
New SARS-CoV-2 variants are continuously emerging with critical implications for therapies or vaccinations. The 22 N-glycan sites of the Spike protein remain highly conserved among SARS-CoV-2 variants, opening an avenue for robust therapeutic intervention. By using a nanomechanical force-sensing approach, we obtained real-time information about the molecular bonds involved in the binding of carbohydrate-binding proteins, so-called lectins, to viral spike proteins. We determined the binding capacity of a molecularly engineered lectin cloned from banana, BanLec H84T, which was shown to display broad-spectrum antiviral activity against several RNA viruses. Our studies revealed that H84T-BanLec interacts with the Spike protein of the original viral strain, Wuhan-1 and several variants of concern (Delta, Omicron). Based on our force probing technique, dynamic molecular interaction patterns with accurate rupture force and length distributions were depicted. The complex multiple binding features between the dimeric H84T and trimeric spike protein were analysed with respect to the distribution of the glycosylation sites on the spike. Using high speed AFM, we additionally imaged spike proteins complexed with isolated lectin molecules to visualize oligomeric states and complex formation. Our data obtained by AFM techniques elucidate lectin-spike interactions at the single molecule level and uncover candidate receptors involved in spike binding and SARS-CoV-2 infections. The capacity of lectins to block SARS-CoV-2 viral entry holds promise for pan-variant therapeutic interventions.
References
- Identification of lectin receptors for conserved SARS-CoV-2 glycosylation sites, The EMBO Journal (2021) e108375.
- A molecularly engineered, broad-spectrum anti-coronavirus Lectin Inhibits SARS-CoV-2 and MERS-CoV Infection In Vivo, Cell Reports Medicine, 3 (2022) 100774.
| Keywords | Single Molecule, Lectin, Biophysics |
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