tetano
Editor, Senior Moderator
Bioconjug Chem. 2018 Aug 31. doi: 10.1021/acs.bioconjchem.8b00527. [Epub ahead of print]
[h=1]Effective in vivo targeting of influenza virus through a cell-penetrating/fusion inhibitor tandem peptide anchored to plasma membrane.[/h] Figueira TN, Augusto MT, Rybkina K, Stelitano D, Noval MG, Harder OE, Veiga AS, Huey D, Alabi CA, Biswas S, Niewiesk S, Moscona A, Santos NC, Castanho MARB, Porotto M.
[h=3]Abstract[/h] 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 (NP), target relevant infectious tissues in vivo, and reduce viral infectivity upon interaction with the cell membrane. Overall, our data shows that the CPP and the lipid moiety are both required for efficient biodistribution, fusion inhibition, and efficacy in vivo.
PMID: 30169965 DOI: 10.1021/acs.bioconjchem.8b00527
[h=1]Effective in vivo targeting of influenza virus through a cell-penetrating/fusion inhibitor tandem peptide anchored to plasma membrane.[/h] Figueira TN, Augusto MT, Rybkina K, Stelitano D, Noval MG, Harder OE, Veiga AS, Huey D, Alabi CA, Biswas S, Niewiesk S, Moscona A, Santos NC, Castanho MARB, Porotto M.
[h=3]Abstract[/h] 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 (NP), target relevant infectious tissues in vivo, and reduce viral infectivity upon interaction with the cell membrane. Overall, our data shows that the CPP and the lipid moiety are both required for efficient biodistribution, fusion inhibition, and efficacy in vivo.
PMID: 30169965 DOI: 10.1021/acs.bioconjchem.8b00527