Fusion Inhibitory Lipopeptides Engineered for Prophylaxis of Nipah Virus in Primates.
Fusion Inhibitory Lipopeptides Engineered for Prophylaxis of Nipah Virus in Primates. J Infect Dis. 2018 Mar 16. doi: 10.1093/infdis/jiy152. [Epub ahead of print]
Mathieu C1,2,3, Porotto M1,2, Figueira T1,2,4, Horvat B3, Moscona A1,2,5,6.
Découvrez l’équipe “Immunologie des Infections virales” dirigée par Branka Horvat
The emerging zoonotic paramyxovirus Nipah virus (NiV) causes severe respiratory and neurological disease in humans, with high fatality rates. NiV can be transmitted via person-to-person contact, posing a high risk for epidemic outbreaks. However, a broadly applicable approach for human NiV outbreaks in field settings is lacking.
We engineered new antiviral lipopeptides and analyzed in vitro fusion inhibition to identify an optimal candidate for prophylaxis of NiV infection in the lower respiratory tract, and assessed antiviral efficiency in two different animal models.
We show that lethal NiV infection can be prevented with lipopeptides delivered via the respiratory route in both hamsters and non-human primates. By targeting retention of peptides for NiV prophylaxis in the respiratory tract, we avoid its systemic delivery in individuals who need only prevention, and thus increase the safety of treatment and enhance utility of the intervention.
The experiments provide a proof of concept for the use of anti-fusion lipopeptides for prophylaxis of lethal NiV. These results advance towards the goal of rational development of potent lipopeptide inhibitors with desirable pharmacokinetic and biodistribution properties and a safe effective delivery method to target NiV and other pathogenic viruses.
Affiliations des auteurs :
1-Department of Pediatrics, Columbia University Medical Center, New York NY.
2-Center for Host-Pathogen Interaction, Columbia University Medical Center.
3-CIRI, International Center for Infectiology Research, Immunobiology of Viral Infections team), Inserm, University Claude Bernard Lyon, CNRS, Ecole Normale Supérieure de Lyon, France.
4-Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, Lisbon, Portugal.
5-Department of Microbiology & Immunology, Columbia University Medical Center.
6-Department of Physiology & Biophysics, Columbia University Medical Center.