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Molecular interaction and inhibition of SARS-CoV-2 binding to the ACE2 receptor

Author

Listed:
  • Jinsung Yang

    (Université Catholique de Louvain)

  • Simon J. L. Petitjean

    (Université Catholique de Louvain)

  • Melanie Koehler

    (Université Catholique de Louvain)

  • Qingrong Zhang

    (Université Catholique de Louvain)

  • Andra C. Dumitru

    (Université Catholique de Louvain)

  • Wenzhang Chen

    (University of Namur)

  • Sylvie Derclaye

    (Université Catholique de Louvain)

  • Stéphane P. Vincent

    (University of Namur)

  • Patrice Soumillion

    (Université Catholique de Louvain)

  • David Alsteens

    (Université Catholique de Louvain
    Walloon Excellence in Life sciences and Biotechnology (WELBIO))

Abstract

Study of the interactions established between the viral glycoproteins and their host receptors is of critical importance for a better understanding of virus entry into cells. The novel coronavirus SARS-CoV-2 entry into host cells is mediated by its spike glycoprotein (S-glycoprotein), and the angiotensin-converting enzyme 2 (ACE2) has been identified as a cellular receptor. Here, we use atomic force microscopy to investigate the mechanisms by which the S-glycoprotein binds to the ACE2 receptor. We demonstrate, both on model surfaces and on living cells, that the receptor binding domain (RBD) serves as the binding interface within the S-glycoprotein with the ACE2 receptor and extract the kinetic and thermodynamic properties of this binding pocket. Altogether, these results provide a picture of the established interaction on living cells. Finally, we test several binding inhibitor peptides targeting the virus early attachment stages, offering new perspectives in the treatment of the SARS-CoV-2 infection.

Suggested Citation

  • Jinsung Yang & Simon J. L. Petitjean & Melanie Koehler & Qingrong Zhang & Andra C. Dumitru & Wenzhang Chen & Sylvie Derclaye & Stéphane P. Vincent & Patrice Soumillion & David Alsteens, 2020. "Molecular interaction and inhibition of SARS-CoV-2 binding to the ACE2 receptor," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18319-6
    DOI: 10.1038/s41467-020-18319-6
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    Cited by:

    1. Zhenzhen Wang & Shiqi Hu & Kristen D. Popowski & Shuo Liu & Dashuai Zhu & Xuan Mei & Junlang Li & Yilan Hu & Phuong-Uyen C. Dinh & Xiaojie Wang & Ke Cheng, 2024. "Inhalation of ACE2-expressing lung exosomes provides prophylactic protection against SARS-CoV-2," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Utku Goreke & Ayesha Gonzales & Brandon Shipley & Madeleine Tincher & Oshin Sharma & William J. Wulftange & Yuncheng Man & Ran An & Michael Hinczewski & Umut A. Gurkan, 2024. "Motion blur microscopy: in vitro imaging of cell adhesion dynamics in whole blood flow," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    3. Jian Rong & Ahmed Haider & Troels E. Jeppesen & Lee Josephson & Steven H. Liang, 2023. "Radiochemistry for positron emission tomography," Nature Communications, Nature, vol. 14(1), pages 1-23, December.
    4. Andreia L. Pinto & Ranjit K. Rai & Jonathan C. Brown & Paul Griffin & James R. Edgar & Anand Shah & Aran Singanayagam & Claire Hogg & Wendy S. Barclay & Clare E. Futter & Thomas Burgoyne, 2022. "Ultrastructural insight into SARS-CoV-2 entry and budding in human airway epithelium," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    5. Alexander J. Pak & Alvin Yu & Zunlong Ke & John A. G. Briggs & Gregory A. Voth, 2022. "Cooperative multivalent receptor binding promotes exposure of the SARS-CoV-2 fusion machinery core," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    6. Rong Zhu & Daniel Canena & Mateusz Sikora & Miriam Klausberger & Hannah Seferovic & Ahmad Reza Mehdipour & Lisa Hain & Elisabeth Laurent & Vanessa Monteil & Gerald Wirnsberger & Ralph Wieneke & Robert, 2022. "Force-tuned avidity of spike variant-ACE2 interactions viewed on the single-molecule level," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    7. Melanie Koehler & Ankita Ray & Rodrigo A. Moreira & Blinera Juniku & Adolfo B. Poma & David Alsteens, 2021. "Molecular insights into receptor binding energetics and neutralization of SARS-CoV-2 variants," Nature Communications, Nature, vol. 12(1), pages 1-13, December.

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