tetano
Editor, Senior Moderator
Nat Commun
. 2023 Feb 4;14(1):620.
doi: 10.1038/s41467-023-36279-5.
Direct Cryo-ET observation of platelet deformation induced by SARS-CoV-2 spike protein
Christopher Cyrus Kuhn[SUP] 1 [/SUP], Nirakar Basnet[SUP] #[/SUP][SUP] 1 [/SUP], Satish Bodakuntla[SUP] #[/SUP][SUP] 1 [/SUP], Pelayo Alvarez-Brecht[SUP] #[/SUP][SUP] 1 2 [/SUP], Scott Nichols[SUP] 1 [/SUP], Antonio Martinez-Sanchez[SUP] 2 3 [/SUP], Lorenzo Agostini[SUP] 1 [/SUP], Young-Min Soh[SUP] 1 [/SUP], Junichi Takagi[SUP] 4 [/SUP], Christian Biertümpfel[SUP] 1 [/SUP], Naoko Mizuno[SUP] 5 6 [/SUP]
Affiliations
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 α[SUB]v[/SUB]β[SUB]3[/SUB]. 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.
. 2023 Feb 4;14(1):620.
doi: 10.1038/s41467-023-36279-5.
Direct Cryo-ET observation of platelet deformation induced by SARS-CoV-2 spike protein
Christopher Cyrus Kuhn[SUP] 1 [/SUP], Nirakar Basnet[SUP] #[/SUP][SUP] 1 [/SUP], Satish Bodakuntla[SUP] #[/SUP][SUP] 1 [/SUP], Pelayo Alvarez-Brecht[SUP] #[/SUP][SUP] 1 2 [/SUP], Scott Nichols[SUP] 1 [/SUP], Antonio Martinez-Sanchez[SUP] 2 3 [/SUP], Lorenzo Agostini[SUP] 1 [/SUP], Young-Min Soh[SUP] 1 [/SUP], Junichi Takagi[SUP] 4 [/SUP], Christian Biertümpfel[SUP] 1 [/SUP], Naoko Mizuno[SUP] 5 6 [/SUP]
Affiliations
- PMID: 36739444
- DOI: 10.1038/s41467-023-36279-5
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 α[SUB]v[/SUB]β[SUB]3[/SUB]. 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.