2023-05-24 22:02:59
Dompé farmaceutici today announced new peer-reviewed data demonstrating that small changes in the SARS-CoV-2 spike (S) protein sequence can reverse its clot-inducing effect1. The spike protein’s tendency to stimulate inflammation and clotting has been linked to the coagulopathy observed in the lungs, heart and kidneys of COVID-19 patients, with similar and extremely rare effects observed in a minority of patients who contracted COVID -19 vaccines received.
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Data from the EXSCALATE supercomputing calculation predicted a possible function of spike (S) as a cofactor for human ERα nuclear signaling. This interaction is mediated by an LXD-like nuclear receptor co-regulator (NRC) motif present on the S2 subunit of the viral protein and in the activation function 2 (AF-2) region on ERα 2. This work builds on other recent studies3,4 show that coagulopathy is clearly related to the interaction of the SARS-CoV-2 spike (S) protein with the human Erα. While circulating estrogens play a protective role by regulating the immune response to infection, modulation of ERα signaling in SARS-CoV-2-infected lung tissue stimulates pro-inflammatory signals leading to hypertrophy, vasoconstriction, and vascular occlusion.
In the new article, the scientists of the Italian-American joint project (with the Centro Cardiologico Monzino in Italy and the National Institute on Drug Abuse and the Johns Hopkins School of Medicine in the USA) showed that the interaction between the spike protein and ERα increases in tissue factor (TF) and general procoagulant activity in two human endothelial cell lines. The results were confirmed by overexpression of S protein in mice. This procoagulant function of Spike in vitro and in vivo was depleted or greatly reduced (as predicted by EXSCALATE) in variants of the Spike proteins carrying mutations in the interaction domain with ERα.
“The value and usefulness of vaccines in combating the COVID-19 pandemic remains undeniable and overwhelming when compared to the risks associated with infection by SARS-CoV-2,” emphasizes Maurizio Pesce, research group leader at the Monzino Cardiology Center in Milan, Italy and initiator of the study in 2021, which he co-led with Silvia Barbieri, another research group leader at Monzino: “We hope that our results will be taken into account in the development of the next generation of vaccines to reduce the remaining side effects and risks reduce.” Our data also reveal a novel function of the viral protein in the direct regulation of thrombosis-associated factors. This has far-reaching implications not only for COVID-19 but also for other viral infections that alter the coagulation profile of patients.”
“This ongoing research is critical to understanding the pathogenetic mechanisms associated with SARS-CoV2 infection and the causal mechanisms of some rare COVID-19 vaccine side effects,” says Marcello Allegretti, Chief Scientific Officer of Dompé farmaceutici. “The continuously growing data show a well conserved region with the same properties of the LXD-like motif present on the S2 subunit of the viral protein also in other coronaviruses. This evidence could open up new scenarios for “pan-coronavirus” vaccination. We are excited to identify a path for further refinement strategies to enable even greater benefits through future vaccination and booster initiatives.”
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About Dompe
Dompé is a private, fast-growing international biopharmaceutical company based in Milan, Italy, with a heritage of 130 years of medical innovation. The company’s R&D department relies on EXSCALATE, an in-house developed structure-based virtual screening platform that leverages one of the most powerful supercomputing and AI platforms in the world. Today, Dompé employs more than 800 people worldwide and maintains a US commercial center in the San Francisco Bay Area and a research and development presence in Boston.
Forward-Looking Statements
This press release contains certain information that may not reflect anticipated future results. Dompé firmly believes in the solidity and reasonableness of the concepts presented. However, some information is subject to a degree of uncertainty related to its research and development activities and required verifications by regulators. Therefore, at this time, Dompé cannot guarantee that the results will match the information above as expected.
1. SS Barbieri et al. Relevance of the viral Spike protein/cellular Estrogen Receptor-α interaction for endothelial-based coagulopathy induced by SARS-CoV-2 – Signal Transduction and Targeted Therapy –
2. Allegretti, M. et al. Repurposing the estrogen receptor modulator raloxifene to treat SARS-CoV-2 370 infection. Cell Death Differ. 29, 156-166 (2022). 371 –
3. Wilcox et al. Sex Differences in Thrombosis and Mortality in Patients Hospitalized for COVID-19, Am J Cardiol. 2022 May 1; 170: 112–117 –
4. Science Advances – The SARS-CoV-2 spike protein binds and modulates estrogen receptors – eadd4150 (2022) 30 November 2022 –
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Medienkontakte – Dompé pharmaceuticals
Guido Romeo – Head Corporate Communications
Phone: +39 349 4154010 |[email protected]
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