Effective in Vivo Targeting of Influenza Virus through a Cell-Penetrating/Fusion Inhibitor Tandem Peptide Anchored to the Plasma Membrane
| Autor: | Olivia Harder, Maria Gabriela Noval, Debora Stelitano, Tiago N. Figueira, Anne Moscona, Christopher A. Alabi, Nuno C. Santos, Sudipta Biswas, Devra Huey, Stefan Niewiesk, Ana Salomé Veiga, Miguel A. R. B. Castanho, Matteo Porotto, Ksenia Rybkina, Marcelo T. Augusto |
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| Přispěvatelé: | Figueira, T. N., Augusto, M. T., Rybkina, K., Stelitano, D., Noval, M. G., Harder, O. E., Veiga, A. S., Huey, D., Alabi, C. A., Biswas, S., Niewiesk, S., Moscona, A., Santos, N. C., Castanho, M. A. R. B., Porotto, M., Repositório da Universidade de Lisboa |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
030106 microbiology Cell Biomedical Engineering Pharmaceutical Science Hemagglutinin (influenza) Biological Availability Bioengineering Hemagglutinin Glycoproteins Influenza Virus Cell-Penetrating Peptides Antiviral Agents Membrane Fusion Virus Article 03 medical and health sciences Immunocompromised Host Viral Proteins In vivo Influenza prevention Pandemic medicine Animals Humans Amino Acid Sequence Sigmodontinae Administration Intranasal Pharmacology biology Chemistry Organic Chemistry Cell Membrane Virology Endocytosis 3. Good health Vaccination 030104 developmental biology medicine.anatomical_structure Influenza A virus Cell-penetrating peptide biology.protein Nanoparticles tat Gene Products Human Immunodeficiency Virus Biotechnology |
| Zdroj: | Bioconjugate Chemistry Repositório Científico de Acesso Aberto de Portugal Repositório Científico de Acesso Aberto de Portugal (RCAAP) instacron:RCAAP |
| ISSN: | 1043-1802 |
| DOI: | 10.1021/acs.bioconjchem.8b00527 |
| Popis: | © 2018 American Chemical Society 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. M.P. acknowledges grants R01AI121349 and R01AI119762 funded by the National Institutes of Health (NIH). T.N.F. acknowledges individual fellowships SFRH/BD/5283/2013 funded by Fundação para a Ciência e a Tecnologia (FCTMCTES). A.S.V. acknowledges funding under the Investigator Programme (IF/00803/2012) from FCT-MCTES. This work was supported by FCT-MCTES projects PTDC/QEQ-MED/4412/2014 and PTDC/BBB-BQB/3494/2014 |
| Databáze: | OpenAIRE |
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