Deciphering ACE-2-Mediated SARS-COV-2 Lung Infection

Difficulty breathing due to severe pneumonia is by far, the most life-threatening emergency symptom reported for COVID-19. This is because the SARS-CoV-2 virus accesses host cells via the enzyme ACE2, which is most abundant in the alveolar cells of the lungs. We aim to study SARS-CoV-2 receptor ACE2 to identify the regions / residues critical for an efficient cell entry. We also aim to determine how the genetic variants / polymorphisms of main ACE2 receptor found in Spanish population and different tissues impinge on SARS-CoV-2 infection capacity. This have a clear therapeutic applications (eg development of ACE2 peptide comprising the critical region as a viral attachment inhibitor and prospective antibody generation) and can be easily transferred to the clinic as it cold explain why different patients have a different susceptibility, symptoms, and outcome of COVID19 depending on the ACE2 polymorphisms. Finaly in an unprecedented analysis of the COVID19 desease in human lung epitheliym, we will make use of CRISPR / Cas9 to study how ACE2-CoV-2 infection affects epithelial organization, cells most susceptible to infection and we will confirm the previous finding in a totally translational / bench-to-bedside approach.