Force-tuned avidity of spike variant-ACE2 interactions viewed on the single-molecule level
- Author(s)
- Rong Zhu, Daniel Canena, Mateusz Sikora, Miriam Klausberger, Hannah Seferovic, Ahmad Reza Mehdipour, Lisa Hain, Elisabeth Laurent, Vanessa Monteil, Gerald Wirnsberger, Ralph Wieneke, Robert Tampé, Nikolaus F. Kienzl, Lukas Mach, Ali Mirazimi, Yoo Jin Oh, Josef M. Penninger, Gerhard Hummer, Peter Hinterdorfer
- 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.
- Organisation(s)
- Computational and Soft Matter Physics
- External organisation(s)
- Johannes Kepler Universität Linz, Max-Planck-Institut für Biophysik, Jagiellonian University in Krakow, Universität für Bodenkultur Wien, Ghent University , Karolinska Institute, APEIRON Biologics AG, Johann Wolfgang Goethe-Universität Frankfurt am Main, National Veterinary Institute, Österreichische Akademie der Wissenschaften (ÖAW), University of British Columbia (UBC)
- Journal
- Nature Communications
- Volume
- 13
- No. of pages
- 17
- ISSN
- 2041-1723
- DOI
- https://doi.org/10.1038/s41467-022-35641-3
- Publication date
- 12-2022
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 106006 Biophysics, 106002 Biochemistry, 106022 Microbiology
- ASJC Scopus subject areas
- Chemistry(all), Biochemistry, Genetics and Molecular Biology(all), General, Physics and Astronomy(all)
- Portal url
- https://ucris.univie.ac.at/portal/en/publications/forcetuned-avidity-of-spike-variantace2-interactions-viewed-on-the-singlemolecule-level(a8719c88-2997-4bc7-bb6b-a5c1dee6d91a).html