University of Cagliari
Development of Novel Endosome-Targeted Ebola Virus Entry Inhibitors as Antiviral Agents - Measles fusion machinery is dysregulated in neuropathogenic variants - Prevention of measles virus infection by intranasal delivery of fusion inhibitor peptides
06 July 2015
Dipartimento di scienze biomediche
PROGRAMMA VISITING PROFESSOR 2015
Finanziamento Regione Autonoma della Sardegna
Ministero dell’Istruzione, dell’Università e della Ricerca
In occasione della presenza in UNICA del Visiting professor
Prof. Matteo Porotto, Ph.D.
Associate Professor of microbiology in Pediatrics
Weill Medical College, Cornell University New York
Si terranno I seguenti seminari
LUNEDI’ 6 LUGLIO CITTADELLA DI MONSERRATO ore 15.30 ASSE E- AULA 9
TITOLO: Development of Novel Endosome-Targeted Ebola Virus Entry Inhibitors as Antiviral Agents
ABSTRACT: Ebola virus membrane fusion and its inhibition: Infection by filoviruses requires membrane fusion between the viral envelope and the endosomal membrane, a process that is mediated by the viral envelope glycoprotein. Fusion-inhibitory peptides block viral fusion and entry in a dominant-negative manner by binding to the fusion intermediate, preventing viral entry. However, the intracellular location of the fusion process makes it challenging to develop peptide fusion inhibitors against Ebola. We target the internalized Ebola virus by adding a cell penetrating peptide sequence and a lipid moiety to the inhibitory peptides to promote their membrane attachment and endocytosis into endosome, along with the virus. We have shown that our peptide inhibits live infection with Ebola in vitro with an IC50 of 0.8 uM and protects 80% of mice from lethal infection with Ebola.
Lunedi’ 3 agosto teatro anatomico via Ospedale ore 15.30
Measles fusion machinery is dysregulated in neuropathogenic variants
Abstract: Measles virus has become a concern in the United States and Europe due to recent outbreaks and continues to be a significant global problem. While live immunization is available, there are no effective therapies or prophylactics to combat measles infection in unprotected people. Additionally, vaccination does not adequately protect immunocompromised people, who are vulnerable to the more severe CNS manifestations of disease. We found that strains isolated from patients with measles virus infection of the CNS have fusion properties different from those of strains previously isolated from patients without CNS involvement. Specifically, the viral entry machinery is more active and the virus can spread, even in the absence of H. Our findings are consistent with an intrahost evolution of the fusion machinery that leads to neuropathogenic MV variants.
Settembre 2015 data e aula da definire
Prevention of measles virus infection by intranasal delivery of fusion inhibitor peptides.
Abstract: Measles virus (MV) infection causes an acute illness that may be associated with infection of the central nervous system (CNS) and severe neurological disease. No specific treatment is available. We have shown that parenterally delivered fusion-inhibitory peptides protect mice from lethal CNS MV disease. Here we show, using established small-animal models of MV infection, that fusion-inhibitory peptides delivered intranasally provide effective prophylaxis against MV infection. Since the fusion inhibitors are stable at room temperature, this intranasal strategy is feasible even outside health care settings, could be used to protect individuals and communities in case of MV outbreaks, and could complement global efforts to control measles.