Effective in Vivo Targeting of Influenza Virus through a Cell-Penetrating/Fusion Inhibitor Tandem Peptide Anchored to the Plasma Membrane.

Autor:	Figueira TN; Instituto de Medicina Molecular, Faculdade de Medicina , Universidade de Lisboa , 1649-028 Lisbon , Portugal.; Department of Pediatrics , Columbia University Medical Center , New York , New York 10032 , United States.; Center for Host-Pathogen Interaction , Columbia University Medical Center , New York , New York 10032 , United States., Augusto MT; Instituto de Medicina Molecular, Faculdade de Medicina , Universidade de Lisboa , 1649-028 Lisbon , Portugal.; Department of Pediatrics , Columbia University Medical Center , New York , New York 10032 , United States.; Center for Host-Pathogen Interaction , Columbia University Medical Center , New York , New York 10032 , United States., Rybkina K; Department of Pediatrics , Columbia University Medical Center , New York , New York 10032 , United States., Stelitano D; Department of Pediatrics , Columbia University Medical Center , New York , New York 10032 , United States., Noval MG; Department of Pediatrics , Columbia University Medical Center , New York , New York 10032 , United States., Harder OE; Department of Veterinary Biosciences, College of Veterinary Medicine , The Ohio State University , Columbus , Ohio 43210 , United States., Veiga AS; Instituto de Medicina Molecular, Faculdade de Medicina , Universidade de Lisboa , 1649-028 Lisbon , Portugal., Huey D; Department of Veterinary Biosciences, College of Veterinary Medicine , The Ohio State University , Columbus , Ohio 43210 , United States., Alabi CA; Robert Frederick Smith School of Chemical and Biomolecular Engineering , Cornell University , Ithaca , New York 14853 , United States., Biswas S; Department of Pediatrics , Columbia University Medical Center , New York , New York 10032 , United States.; Center for Host-Pathogen Interaction , Columbia University Medical Center , New York , New York 10032 , United States., Niewiesk S; Department of Veterinary Biosciences, College of Veterinary Medicine , The Ohio State University , Columbus , Ohio 43210 , United States., Moscona A; Department of Pediatrics , Columbia University Medical Center , New York , New York 10032 , United States.; Center for Host-Pathogen Interaction , Columbia University Medical Center , New York , New York 10032 , United States.; Department of Microbiology & Immunology , Columbia University Medical Center , New York , New York 10032 , United States.; Department of Physiology & Cellular Biophysics , Columbia University Medical Center , New York , New York 10032 , United States., Santos NC; Instituto de Medicina Molecular, Faculdade de Medicina , Universidade de Lisboa , 1649-028 Lisbon , Portugal., Castanho MARB; Instituto de Medicina Molecular, Faculdade de Medicina , Universidade de Lisboa , 1649-028 Lisbon , Portugal., Porotto M; Department of Pediatrics , Columbia University Medical Center , New York , New York 10032 , United States.; Center for Host-Pathogen Interaction , Columbia University Medical Center , New York , New York 10032 , United States.; Department of Experimental Medicine , University of Campania 'Luigi Vanvitelli' , 81100 Caserta , Caserta , Italy.
Jazyk:	angličtina
Zdroj:	Bioconjugate chemistry [Bioconjug Chem] 2018 Oct 17; Vol. 29 (10), pp. 3362-3376. Date of Electronic Publication: 2018 Sep 14.
DOI:	10.1021/acs.bioconjchem.8b00527
Abstrakt:	The impact of influenza virus infection is felt each year on a global scale when approximately 5-10% of adults and 20-30% of children globally are infected. While vaccination is the primary strategy for influenza prevention, there are a number of likely scenarios for which vaccination is inadequate, making the development of effective antiviral agents of utmost importance. Anti-influenza treatments with innovative mechanisms of action are critical in the face of emerging viral resistance to the existing drugs. These new antiviral agents are urgently needed to address future epidemic (or pandemic) influenza and are critical for the immune-compromised cohort who cannot be vaccinated. We have previously shown that lipid tagged peptides derived from the C-terminal region of influenza hemagglutinin (HA) were effective influenza fusion inhibitors. In this study, we modified the influenza fusion inhibitors by adding a cell penetrating peptide sequence to promote intracellular targeting. These fusion-inhibiting peptides self-assemble into ∼15-30 nm nanoparticles (NPs), target relevant infectious tissues in vivo, and reduce viral infectivity upon interaction with the cell membrane. Overall, our data show that the CPP and the lipid moiety are both required for efficient biodistribution, fusion inhibition, and efficacy in vivo.
Databáze:	MEDLINE
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