New Study Reveals SARS-CoV-2 Nucleocapsid Protein Triggers Immune Attack on Healthy Cells

Recent research has uncovered a novel mechanism by which the SARS-CoV-2 virus, responsible for COVID-19, may cause tissue damage through immune system misdirection. The study, published in Cell Reports, demonstrates that the virus's nucleocapsid protein (NP), primarily known for packaging viral RNA within infected cells, can be transferred to neighboring uninfected epithelial cells and adhere to their surfaces. This attachment triggers the immune system to mistakenly target these healthy cells, leading to inflammation and cellular destruction.

The researchers found that NP binds specifically to molecules called Heparan Sulfate proteoglycans on cell surfaces, forming clumps that are recognized by antibodies generated during infection. Consequently, the immune system activates the classical complement pathway, resulting in tissue damage that may contribute to severe COVID-19 symptoms and long-term complications such as long COVID.

Using advanced imaging techniques, laboratory-grown cells, and patient samples, the team discovered that the viral protein sticks to healthy cells, and this process can be blocked by enoxaparin, a common blood thinner that mimics heparin. Enoxaparin prevents NP from binding to cell surfaces, thereby reducing immune-mediated attack. These findings open new avenues for therapeutic strategies that mitigate immune damage by targeting viral protein interactions.

The research involved collaboration among scientists at the Hebrew University of Jerusalem, with experiments conducted in specialized biosafety facilities. This groundbreaking work enhances our understanding of COVID-19 pathology and highlights the importance of immune regulation in disease management.

Source: linkinghub.elsevier.com/retrieve/pii/S2211124725002839

For more information, see the full study in Cell Reports.