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

Kuhn, C. C.; Basnet, N.; Bodakuntla, S.; Alvarez- Brecht, P.; Nichols, S.; Martinez-Sanchez, A.; Agostini, L.; Soh, Y.-M.; Takagi, J.; Biertumpfel, C.; Mizuno, N.

doi:10.1101/2022.11.22.517574

bioRxiv · 10.1101/2022.11.22.517574

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

Kuhn, C. C.·Basnet, N.·Bodakuntla, S.·Alvarez- Brecht, P.·Nichols, S.·Martinez-Sanchez, A.·Agostini, L.·Soh, Y.-M.·Takagi, J.·Biertumpfel, C.·Mizuno, N.

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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 showed that the S protein triggers platelets to deform dynamically, in some cases, leading to their irreversible activation. Strikingly, cellular cryo-electron tomography revealed 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 found that S protein recognizes integrin v{beta}3. 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.

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Kuhn, C. C., Basnet, N., Bodakuntla, S., Alvarez- Brecht, P., Nichols, S., Martinez-Sanchez, A., Agostini, L., Soh, Y.-M., Takagi, J., Biertumpfel, C., Mizuno, N.. 2022-11-23. Direct Cryo-ET observation of platelet deformation induced by SARS-CoV-2 Spike protein. https://doi.org/10.1101/2022.11.22.517574

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