Several structural and non-structural proteins of different SARS viruses, including SARS-CoV-2-related SARS-CoV, were reported to modulate autophagy. Accordingly, recent preliminary findings suggest that SARS-CoV-2 can suppress autophagy in bronchial epithelial cells, while pharmacological inhibition of autophagy blocks SARS-CoV-2 cytopathogenic effect in Vero-E6 kidney epithelial cells. However, the contribution of individual SARS-CoV-2 proteins in these effects, sensitivity of other relevant cell types (e.g. monocytes/macrophages and endothelial cells) to SARS-CoV-2 autophagy modulation, and its consequences for the inflammatory responses have not been explored.
The main objectives of our projects are:
1. To determine the effects of structural and non-structural SARS-CoV-2 proteins on autophagy and immune response in human host cells exposed to viral RNA mimics and identify the underlying molecular mechanisms (work package-WP1 and 2).
2. To define the interaction between autophagy and innate/antiviral immune responses in target cells harboring SARS-CoV-2 proteins and identify the underlying molecular mechanisms (WP3).
3. To correlate autophagy markers with immune profile of COVID-19 patients and disease severity/outcome (WP4).
4. Informisati naučne i medicinske radnike, pacijenate, kao i širu javnosti o ulozi autofagije u COVID-19 i u sličnim imunološkim poremećajima (RP5).