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

National Heart, Lung, And Blood Institute

Investigators

Linked publications, trials & patents

Abstract

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. Particularly, prominent effects were shown under collagen-I ECM background. 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 including sub-tomogram averaging up to 12 resolution 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. We demonstrated the SARS-CoV-2 spike protein has a weak affinity to a5b1 as well as avb3, but not aIIbb3 integrin receptors. Our results infer that the stochastic activation of platelets is due to weak the interactions of SARS-CoV-2 spike protein with minor integrins expressed on platelet surface, which can attribute to the multilateral pathogenesis of COVID-19 and the occurrence of rare but severe coagulopathies.