PT  - JOURNAL ARTICLE
AU  - Kuhn, Christopher Cyrus
AU  - Basnet, Nirakar
AU  - Bodakuntla, Satish
AU  - Alvarez-Brecht, Pelayo
AU  - Nichols, Scott
AU  - Martinez-Sanchez, Antonio
AU  - Agostini, Lorenzo
AU  - Soh, Young-Min
AU  - Takagi, Junichi
AU  - Biertümpfel, Christian
AU  - Mizuno, Naoko
TI  - Direct Cryo-ET observation of platelet deformation induced by SARS-CoV-2 Spike protein
AID  - 10.1101/2022.11.22.517574
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.11.22.517574
4099  - http://biorxiv.org/content/early/2022/11/23/2022.11.22.517574.short
4100  - http://biorxiv.org/content/early/2022/11/23/2022.11.22.517574.full
AB  - 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 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.Competing Interest StatementThe authors have declared no competing interest.