Modulating SARS-CoV-2 Spike Protein Reactivity through Moderate Electric Fields: A Pathway to Innovative Therapies

Nguyen, Thi-Huong; Wang, Hanqing; Chen, Li-Yu; Echtermeyer, Danny; Pliquett, Uwe

doi:10.1021/acsomega.3c06811

Cited by 2 publications

(1 citation statement)

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“…This investigation could yield insights for future drug design, enabling the development of targeted therapeutics with enhanced precision and efficacy. Recently, modulating SARS-CoV-2 reactivity through electric fields has been reported as a pathway to innovative therapies [ 55 ]. Identifying the precise region within SP that engages with PF4 holds the key to advancing pharmaceutical strategies for PF4-related disorders or even with the application of electric fields.…”

Section: Discussionmentioning

confidence: 99%

The Binding of the SARS-CoV-2 Spike Protein to Platelet Factor 4: A Proposed Mechanism for the Generation of Pathogenic Antibodies

Nguyen,

Chen,

Khan

et al. 2024

Biomolecules

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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/heparin 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 and suggested a reconsideration of current diagnostic assays for the better detection of PF4/SP antibodies. We further validated the changes in zeta potential and interaction affinity between PF4 and SP and found that their binding mechanism differs from ACE2–SP 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.

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Section: Discussionmentioning

confidence: 99%