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Direct Cryo-ET observation of platelet deformation induced by SARS-CoV-2 spike protein

Author

Listed:
  • Christopher Cyrus Kuhn

    (National Institutes of Health)

  • Nirakar Basnet

    (National Institutes of Health)

  • Satish Bodakuntla

    (National Institutes of Health)

  • Pelayo Alvarez-Brecht

    (National Institutes of Health
    University of Oviedo)

  • Scott Nichols

    (National Institutes of Health)

  • Antonio Martinez-Sanchez

    (University of Oviedo
    Avenida Hospital Universitario s/n)

  • Lorenzo Agostini

    (National Institutes of Health)

  • Young-Min Soh

    (National Institutes of Health)

  • Junichi Takagi

    (Osaka University)

  • Christian Biertümpfel

    (National Institutes of Health)

  • Naoko Mizuno

    (National Institutes of Health
    National Institutes of Health)

Abstract

SARS-CoV-2 is a novel coronavirus responsible for the COVID-19 pandemic. Its high pathogenicity is due to SARS-CoV-2 spike protein (S protein) contacting host-cell receptors. A critical hallmark of COVID-19 is the occurrence of coagulopathies. Here, we report the direct observation of the interactions between S protein and platelets. Live imaging shows that the S protein triggers platelets to deform dynamically, in some cases, leading to their irreversible activation. Cellular cryo-electron tomography reveals dense decorations of S protein on the platelet surface, inducing filopodia formation. Hypothesizing that S protein binds to filopodia-inducing integrin receptors, we tested the binding to RGD motif-recognizing platelet integrins and find that S protein recognizes integrin αvβ3. Our results infer that the stochastic activation of platelets is due to weak interactions of S protein with integrin, which can attribute to the pathogenesis of COVID-19 and the occurrence of rare but severe coagulopathies.

Suggested Citation

  • Christopher Cyrus Kuhn & Nirakar Basnet & Satish Bodakuntla & Pelayo Alvarez-Brecht & Scott Nichols & Antonio Martinez-Sanchez & Lorenzo Agostini & Young-Min Soh & Junichi Takagi & Christian Biertümpf, 2023. "Direct Cryo-ET observation of platelet deformation induced by SARS-CoV-2 spike protein," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36279-5
    DOI: 10.1038/s41467-023-36279-5
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