The virus SARS-CoV-2 is highly pathogenic because of the way its spike protein (S protein) interacts with host-cell receptors. The disease it causes, COVID-19, is often associated with low platelet counts and excessive blood clotting, leading to myocardial infarction in severe cases. This study employed electron cryotomography (CryoET)—an imaging technique used to produce high-resolution three-dimensional views of biological macromolecules and cells—to offer a direct observation of the interaction between S proteins and platelets. The authors reported that this interaction triggers platelet deformation in some instances, which leads to their irreversible activation and in rare cases, the excessive blood clotting seen in severe COVID-19 cases. 

What is exciting about this article?

The abnormal blood clotting seen in severe COVID-19 cases may lead to cardiovascular complications, respiratory failure, and multiple organ failures. In this study, the researchers found that SARS-CoV-2 spike protein binds to platelet integrin receptors to trigger platelet deformation. Exposure to S protein also primed these blood cells for activation upon exposure to additional stimuli that are also active during infection, leading to rare but severe blood coagulation in critical cases.

How does this fit into the larger NIAMS portfolio?

The goal of Dr. Mizuno's research is to understand the molecular mechanisms of dynamic morphological changes in platelets. This article not only sheds light on how SARS-CoV-2 infection leads to abnormal thrombosis, but also demonstrates the power of direct imaging at molecular resolution.

Grant support


Research Areas:

Cell Biology Structural Biology


Direct Cryo-ET observation of platelet deformation induced by SARS-CoV-2 spike protein.

Kuhn CC, Basnet N, Bodakuntla S, Alvarez-Brecht P, Nichols S, Martinez-Sanchez A, Agostini L, Soh YM, Takagi J, Biertümpfel C, Mizuno N
Nat Commun.
2023 Feb 4;
doi: 10.1038/s41467-023-36279-5
PMID: 36739444

Research reported in this publication was supported by the Intramural Research Program of the NIHʼs National Institute of Arthritis and Musculoskeletal and Skin Diseases.