CORNELL UNIVERSITY - Morra (DCM.AD008.054)
Project areaModelling computazionale (DCM.AD008)
Structure responsible for the research project
Envelope viruses infect cells via fusion of the viral envelope membrane with cellular membranes. This process is mediated by fusion proteins on the virus surface and requires proteolytic cleavage steps resulting in exposure of a fusion peptide (FP), which inserts into the target membrane. FP insertion results in destabilization of the target membrane and constitutes an essential step for membrane fusion and viral entry. In coronaviruses, the surface spike glycoprotein serves as the fusion protein, and the FP is found in a bipartite form consisting of a helical segment (FP1) and an internal loop (FP2). Our collaborators have shown that the SARS-CoV-1 FP contains critical conserved acidic residues, binds calcium ions, and perturbs membranes in a calcium-dependent fashion. This suggests that calcium, enriched in endosomes and lysosomes, plays a crucial role in SARS-CoV-1 infectivity. SARS-CoV-2, responsible for the recent COVID-19 epidemic, is homologous to SARS-CoV-1 in many regions, including the FP, which differs in only three positions. We hypothesize that the SARS-CoV-2 FP also binds calcium and that calcium is a critical determinant of FP membrane binding and perturbation...
Start date of activity
Sars-Cov2, drug discovery, computational modelling
Last update: 03/12/2023