SARS-CoV-2 spike protein-associated sialoglycoconjugates induce nanoscale filipodia to facilitate micro-size platelet clotting
Bake, A.; Sanaubarova, A.; Spillings, B. L.; Bremaud, E.; Masic, V.; Dirr, L.; von Itzstein, M.; Mak, J.
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COVID-19 disease is associated with thrombosis, but the pathogenic mechanism remains unclear. Here, we investigate how SARS-CoV-2 spike protein causes platelet activation and aggregation. Our three-dimensional ultrastructural analyses showed that invaginated platelet structures, open canalicular system (OCS), expanded upon activation, trapping viral particles in the process. Binding with platelet OCS concealed SAR-CoV-2 spike-coated particles from virion detection in platelet-depleted blood plasma. Both SARS-CoV-2 spike coated-particles and recombinant spikes specifically induced platelet aggregation with nanoscale filipodia extensions, with the terminal sialic acids of the SARS-CoV-2 spike protein-associated sialoglycoconjugates being the key determinant in platelet activation. Our work illustrates that virus-associated sialic acids, not proteins, are functionally responsible for SARS-CoV-2 induced thrombotic events, providing a mechanistic insight on how glycosylation contributes to disease severity in COVID-19. This study lays the foundation for the development of glycan-modified vaccines with reduced risks of thrombosis.
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