CORONA - CORONAmem - Molecular determinants of differential host susceptibility to SARS-CoV-2 at the point of entry.

This project will contribute to the management of the corona crisis. One of the most striking features of the Covid 19 outbreak is the tremendous variation in individual susceptibility to the virus. Coronaviruses gain access by binding host membrane proteins via the viral membrane envelope spike protein (S protein). Therefore, the interaction of the S protein with the host cell represents a Trojan horse to enable viral infection. One goal of this proposal is to characterize the interactions of the S protein with genetic variants of host membrane proteins, both structurally and biophysically. The knowledge gained will allow us to better understand why individuals respond so differently to the virus. This may allow classification of at-risk patients and pave the way for personalized therapies. Since the lipid composition of the host cell is dependent on the tissue as well as the age, dietary habits and previous diseases of the host, studies on the dependence of membrane binding of the spike protein on lipid composition should provide insights into why certain populations are more susceptible to infection with SARS-CoV-2, regardless of their genetic background. Therefore, r the interactions of the S protein with model membranes should be investigated to analyze the influence of lipid composition on protein-membrane interactions.