The Effect of SARS-CoV-2 on Vascular Permeability

The SARS-CoV-2 transmembrane accessory protein ORF7a has been modelled to bind to the T-lymphocyte LFA-1 integrin receptor. This receptor is usually involved in activation of T-lymphocytes and transmigration by interacting with the endothelial cell surface ICAM-1 receptor to facilitate firm adhesion. We are looking to study this interaction, to see if the in-silico models are accurate and if they have an observable effect on cell function. We will also assess if inhibition of the LFA-1:ORF7a interaction has any translatable benefit. Additionally, we will be analysing the SARS-CoV-2 nucleocapsid protein. This protein is involved in the encapsulation of the viral genome and uses host protein kinases to phosphorylate its SR rich region to affect binding affinities of the CTD and NTD to the viral genome, a process which is required during viral replication. Our approach to studying this interaction is to first work with recombinant ORF7a, assessing if the interaction can cause firm adhesion to endothelial cells in addition to doing in-vitro assays on nucleocapsid phosphorylation. Following on from this we will move onto live SARS-CoV-2 and in-vivo work to see if any results are translatable to the whole virus.