A recent study from the Faculty of Medicine at the Hebrew University of Jerusalem has uncovered significant insights into the mechanisms by which the SARS-CoV-2 virus, responsible for COVID-19, may cause immune-mediated tissue damage. Conducted by a collaborative team of researchers, including PhD students Jamal Fahoum and Maria Billan, the research highlights the role of the virus's nucleocapsid protein (NP) in triggering unwanted immune responses.
Published in the journal Cell Reports, the study reveals that the NP can spread from infected cells to neighboring uninfected cells, binding to their surfaces. This interaction falsely signals the immune system to target these healthy cells, activating the classical complement pathway and potentially leading to inflammation and tissue damage. This misdirection of the immune response may significantly contribute to severe COVID-19 outcomes and complications, including long COVID.
The research utilized advanced imaging techniques and samples from COVID-19 patients to analyze how NP attaches to healthy cells via specific sugar-like molecules known as Heparan Sulfate proteoglycans. The formation of protein clumps on healthy cells subsequently triggers an immune attack, which can harm both infected and uninfected cells.
Importantly, the study also identified the anticoagulant enoxaparin as a potential therapeutic intervention. By occupying the binding sites of the NP, enoxaparin can prevent the protein from attaching to healthy cells, thereby reducing the risk of immune misfires. Laboratory tests demonstrated that this drug effectively inhibited NP's harmful interactions.
These findings pave the way for new strategies aimed at mitigating immune-driven damage in COVID-19 and other viral infections, with ongoing research expected to explore these avenues further. The study was supported by various research funds and dedicated to the memory of the late Prof. Hervé Bercovier, a prominent microbiologist.