SARS-COV2 nuclear protein binds epithelial cells through their proteoglycans

Jamal Fahoum ^1,2 Julia Varga ¹ Maria Billan ¹ Sujata Kumari ^1,2 Alexander Rouvinski ¹ Reuven Wiener ² Ora Schueler-Furman ¹

¹Department of Microbiology and Molecular Genetics, Institute of Medical Research Israel-Canada, The Hebrew University of Jerusalem,, Israel
²Department of Biochemistry and Molecular Biology, Institute of Medical Research Israel-Canada, The Hebrew University of Jerusalem,, Israel

Patients with SARS-CoV-2 develop antibodies to the virus, and these antibodies are not only targeting the surface protein/antigens of the virus but also the inner proteins such as the nucleocapsid (N) protein. It has been found that the N protein is so immunogenic and stands out as the most important diagnostic antigen of the virus. The main known function of the N protein is to package the viral genome. In our study we are showing that the N protein may play a role in activating the complement system by binding to the epithelial cells and suggesting that it can exacerbate the disease through killing these cells. Also, we are showing that this binding is mediated through electrostatic interactions to a putative heparin-sulfate proteoglycans (HSPGs). Furthermore, soluble heparin analogs compete with N protein binding to the membrane of healthy cells. These findings uncover a new role of the N protein in the disease development and may help to find an effective vaccine.