Speaker
Description
Recent waves of COVID-19 correlate with the emergence of the Delta and the Omicron variant. In this study, we combined high-speed atomic force microscopy with single molecule recognition force spectroscopy to investigate, at single molecule resolution, the interaction dynamics of trimeric Spike with its essential entry receptor ACE2. We report that the Spike trimer undergoes rapid conformational changes on surfaces, resulting in arc-like movements of the three receptor binding domains (RBDs) that collectively screen a circular range of almost 360° degrees. Acting as a highly dynamic molecular caliper, it thereby forms up to three tight bonds through its RBDs with ACE2 expressed on the cell surface. The Spike of both Delta and Omicron (B.1.1.529) Variant enhance and markedly prolong viral attachment to the host cell receptor ACE2, as opposed to the early Wuhan-1 isolate. Delta Spike showed rapid binding of all three Spike RBDs to three different ACE2 molecules with considerably increased bond lifetime when compared to the reference strain, thereby significantly amplifying avidity. Intriguingly, Omicron (B.1.1.529) Spike displayed less multivalent bindings to ACE2 molecules, yet with a ten time longer bond lifetime than Delta. Delta and Omicron (B.1.1.529) Spike variants enhance and prolong viral attachment to the host, which likely not only increases the rate of viral uptake, but also enhances the resistance of the variants against host-cell detachment by shear forces such as airflow, mucus or blood flow. We uncovered distinct binding mechanisms and strategies employed by circulating SARS-CoV-2 variants to enhance infectivity and viral transmission.
References
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| Keywords | AFM, Spike |
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