Progetto di ricerca

CORNELL UNIVERSITY - Morra (DCM.AD008.054)

Area tematica

Scienze chimiche e tecnologie dei materiali

Area progettuale

Modelling computazionale (DCM.AD008)

Struttura responsabile del progetto di ricerca

Istituto di Scienze e Tecnologie Chimiche "Giulio Natta" (SCITEC)

Responsabile di progetto

GIULIA MORRA
Telefono: 0228500031
E-mail: giulia.morra@scitec.cnr.it

Abstract

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...

Data inizio attività

01/01/2021

Parole chiave

Sars-Cov2, drug discovery, computational modelling

Ultimo aggiornamento: 03/03/2024