{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:47:29Z","timestamp":1790754449865,"version":"4.1.0"},"reference-count":55,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T00:00:00Z","timestamp":1708387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["469240103"],"award-info":[{"award-number":["469240103"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Freistaat Th\u00fcringen","award":["469240103"],"award-info":[{"award-number":["469240103"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Pathogenic platelet factor 4 (PF4) antibodies contributed to the abnormal coagulation profiles in COVID-19 and vaccinated patients. However, the mechanism of what triggers the body to produce these antibodies has not yet been clarified. Similar patterns and many comparable features between the COVID-19 virus and heparin-induced thrombocytopenia (HIT) have been reported. Previously, we identified a new mechanism of autoimmunity in HIT in which PF4-antibodies self-clustered PF4 and exposed binding epitopes for other pathogenic PF4\/eparin antibodies. Here, we first proved that the SARS-CoV-2 spike protein (SP) also binds to PF4. The binding was evidenced by the increase in mass and optical intensity as observed through quartz crystal microbalance and immunosorbent assay, while the switching of the surface zeta potential caused by protein interactions and binding affinity of PF4-SP were evaluated by dynamic light scattering and isothermal spectral shift analysis. Based on our results, we proposed a mechanism for the generation of PF4 antibodies in COVID-19 patients. We further validated the changes in zeta potential and interaction affinity between PF4 and SP and found that their binding mechanism differs from ACE2\u2013SP binding. Importantly, the PF4\/SP complexes facilitate the binding of anti-PF4\/Heparin antibodies. Our findings offer a fresh perspective on PF4 engagement with the SARS-CoV-2 SP, illuminating the role of PF4\/SP complexes in severe thrombotic events.<\/jats:p>","DOI":"10.3390\/biom14030245","type":"journal-article","created":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T04:36:22Z","timestamp":1708403782000},"page":"245","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The Binding of the SARS-CoV-2 Spike Protein to Platelet Factor 4: A Proposed Mechanism for the Generation of Pathogenic Antibodies"],"prefix":"10.3390","volume":"14","author":[{"given":"Thi-Huong","family":"Nguyen","sequence":"first","affiliation":[{"name":"Institute for Bioprocessing and Analytical Measurement Techniques (iba), 37308 Heilbad Heiligenstadt, Germany"},{"name":"Faculty of Mathematics and Natural Sciences, Technische Universit\u00e4t Ilmenau, 98694 Ilmenau, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute for Bioprocessing and Analytical Measurement Techniques (iba), 37308 Heilbad Heiligenstadt, Germany"},{"name":"Institute of Miccrobiology, Friedrich-Schiller-University, 07745 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nida Zaman","family":"Khan","sequence":"additional","affiliation":[{"name":"Institute for Bioprocessing and Analytical Measurement Techniques (iba), 37308 Heilbad Heiligenstadt, Germany"},{"name":"Faculty of Mathematics and Natural Sciences, Technische Universit\u00e4t Ilmenau, 98694 Ilmenau, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annerose","family":"Lindenbauer","sequence":"additional","affiliation":[{"name":"Institute for Bioprocessing and Analytical Measurement Techniques (iba), 37308 Heilbad Heiligenstadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2652-4454","authenticated-orcid":false,"given":"Van-Chien","family":"Bui","sequence":"additional","affiliation":[{"name":"Department of Water Supply and Wastewater Treatment, Eichsfeldwerke GmbH, 37308 Heilbad Heiligenstadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6149-2411","authenticated-orcid":false,"given":"Peter F.","family":"Zipfel","sequence":"additional","affiliation":[{"name":"Institute of Miccrobiology, Friedrich-Schiller-University, 07745 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doris","family":"Heinrich","sequence":"additional","affiliation":[{"name":"Institute for Bioprocessing and Analytical Measurement Techniques (iba), 37308 Heilbad Heiligenstadt, Germany"},{"name":"Faculty of Mathematics and Natural Sciences, Technische Universit\u00e4t Ilmenau, 98694 Ilmenau, Germany"},{"name":"Fraunhofer Institut f\u00fcr Silicatforschung, Neunerplatz, 97082 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,20]]},"reference":[{"key":"ref_1","unstructured":"WHO (2023, October 04). 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