Assessing the role of the gene associated with Acrofrontofacionasal Dysostosis type 1, NBAS, in the nonsense mediated decay and Golgi-to-ER retrograde transport functions in Sars-CoV-2 infected cells.

COVID-19 is a severe respiratory disease caused by the novel human coronavirus SARS-CoV-2. When infecting cells, viruses exploit the physiological processes of the host and reframe them to their own advantage; however, the alterations of cell functions determined by SARS-CoV-2 infection are poorly understood. Therefore, our project will investigate specifically the interaction of SARS-CoV-2 with two essential cellular functions (i.e. the nonsense-mediated decay and the retrograde transport from the Golgi to the Endoplasmic Reticulum), based on previous evidence of a mutual influence between viruses and these cellular processes. In particular, we will exploit our knowledge of a rare hereditary skeletal disease, Acrofrontofacionasal Dysostosis Type 1 as we have identified mutations in the NBAS gene that alter both the NMD and the retrograde transport pathways in two affected siblings. Defects in this gene in patients with other rare diseases have been independently reported; interestingly enough, regardless of the diagnosis, frequent lung infections of viral origin have been described in some of these individuals. Altogether this evidence might suggest that NBAS plays a non-redundant role in host susceptibility to viral respiratory infections, potentially including SARS-CoV-2. Thus, we will attempt to clarify the mutual interaction between NBAS and NBAS-related pathways, and SARS-CoV-2 replication and cytopathicity, as a starting point to define new potential targets for antiviral drug discovery.