1. Force-tuned avidity of spike variant-ACE2 interactions viewed on the single-molecule level.
- Author
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Zhu, Rong, Canena, Daniel, Sikora, Mateusz, Klausberger, Miriam, Seferovic, Hannah, Mehdipour, Ahmad Reza, Hain, Lisa, Laurent, Elisabeth, Monteil, Vanessa, Wirnsberger, Gerald, Wieneke, Ralph, Tampé, Robert, Kienzl, Nikolaus F., Mach, Lukas, Mirazimi, Ali, Oh, Yoo Jin, Penninger, Josef M., Hummer, Gerhard, and Hinterdorfer, Peter
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SARS-CoV-2 Delta variant ,SARS-CoV-2 Omicron variant ,MOLECULAR dynamics ,SARS-CoV-2 ,CELL receptors - Abstract
Recent waves of COVID-19 correlate with the emergence of the Delta and the Omicron variant. We report that the Spike trimer acts as a highly dynamic molecular caliper, thereby forming 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 shows 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 displays 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 uncover distinct binding mechanisms and strategies at single-molecule resolution, employed by circulating SARS-CoV-2 variants to enhance infectivity and viral transmission. Combining high-speed AFM, single molecule recognition force spectroscopy, and molecular dynamics simulations Zhu, Canena, Sikora et al. characterize the interaction dynamics of the trimeric spike protein of SARS-CoV-2 wt, and delta and omicron variants with its entry receptor ACE2. While delta variant increases avidity by multivalent binding to ACE2, omicron variant shows an extended binding lifetime. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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