Molecular insights into the effects of SARS-Cov2 infection on the blood system

NIH Pandemic-Era Grants

Pandemic Era Grants

2022

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Principal Investigator: Naoko  Mizuno
Organization: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
Fiscal Year: 2022
Award: $498,022
Funding agency: National Heart Lung and Blood Institute

We hypothesize that SARS-Cov2 directly interacts with neutrophils as well as platelets through their receptors, and induces a change in platelet morphology, leading to their activation and coagulation. We performed live imaging showing that platelets are directly activated in the presence of purified SARS-Cov2 spike protein. We further visualized platelet deformation in the presence of SARS-Cov2 spike protein using cellular cryo-electron tomography (cryo-ET). Strikingly, cellular cryo-ET revealed dense decorations of SARS-CoV-2 spike protein on the platelet surface coinciding with filopodia formation. Further analysis revealed the flexible attachment of the SARS-CoV-2 to the membrane surface, suggesting a great adoptability of the SARS-CoV-2 spike protein to the dynamic membrane surface. We further tested the binding to several platelet receptors and the receptor inhibitors. Our results infer that the stochastic activation of platelets is due to weak the interactions of SARS-CoV-2 spike protein with platelets, which can attribute to the multilateral pathogenesis of COVID-19 and the occurrence of rare but severe coagulopathies.

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