Inhibition of Influenza Virus Infection by a Novel Antiviral Peptide That Targets Viral Attachment to Cells

To inhibit binding of the influenza A virus to the host cell glycocalyx, we generate multivalent peptide–polymer nanoparticles binding with nanomolar affinity to the virus via its spike protein hemagglutinin. The chosen dendritic polyglycerol scaffolds are highly biocompatible and well suited for a multivalent presentation. We could demonstrate in vitro that by increasing the size of the polymer scaffold and adjusting the peptide density, viral infection is drastically reduced. Such a peptide–polymer conjugate qualified also in an in vivo infection scenario. With this study we introduce the first non‐carbohydrate‐based, covalently linked, multivalent virus inhibitor in the nano‐ to picomolar range by ensuring low peptide‐ligand density on a larger dendritic scaffold.

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“…Alternative ligands to SA are peptides targeting HA 24, 25, 26. Peptides may have several advantages, including higher affinity and selectivity.…”

mentioning

confidence: 99%

“…Indeed, in 2006 a peptide derived from the signal sequence of fibroblast growth factor 4 (FGF 4) was shown to inhibit infection by the influenza virus 25. Thereafter, a peptide was optimized for HA binding by selection from a phage‐displayed random peptide library 24.…”

mentioning

confidence: 99%

Multivalent Peptide–Nanoparticle Conjugates for Influenza‐Virus Inhibition

et al. 2017

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“…One, multimeric zanamavir, is in the preclinical stages and the other, DAS181(Fludase), is in Phase I clinical trials [41,42]. Novel entry blocker proteins, such as the 20 amino-acid peptide derived from fibroblast growth factor 4 that blocks viral entry by binding to the HA and exhibits antiviral activity against influenza in tissue culture and in mice are also under investigation [43].…”

Section: Current Pharmacotherapy and Drug Developmentmentioning

confidence: 99%

Pandemic and seasonal influenza: therapeutic challenges

Memoli

Morens

Taubenberger

2008

Drug Discovery Today

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Influenza A viruses cause significant morbidity and mortality annually, and the threat of a pandemic underscores the need for new therapeutic strategies. Here we briefly discuss novel antiviral agents under investigation, the limitations of current antiviral therapy and stress the importance of secondary bacterial infections in seasonal and pandemic influenza. Additionally, the lack of new antibiotics available to treat increasingly drug resistant organisms such as methicillin-resistant Staphylococcus aureus, pneumococci, Acinetobacter, extended spectrum beta-lactamase producing gram negative bacteria and Clostridium difficile is highlighted as an important component of influenza treatment and pandemic preparedness. Addressing these problems will require a multidisciplinary approach, which includes the development of novel antivirals and new antibiotics, as well as a better understanding of the role secondary infections play on the morbidity and mortality due to influenza infection.

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“…eB is a novel 20-amino acid antiviral peptide derived from the signal sequence of fibroblast growth factor 4 and has been shown to bind hemagglutinin and inhibit influenza attachment to recipient cells. 21 We tested the inhibitory activity of eB to hApp entry at several concentrations. As a negative inhibitor control, the sequence-scrambled peptide, eBX, was also tested at similar concentrations.…”

Section: Requirements For Happ Transductionmentioning

confidence: 99%

“…All cells were grown in Dulbecco's modified eagle's medium (Dmem) containing 10% fetal bovine serum (fBS) and penicillin-streptomycin at 37 °C under 5% CO 2 . Peptides eB (RRKKAAvAllPAvllAllAPg) and eBX (RRKKlAAlPlvlAAPlAvlA) 21 were synthesized using ABI 443A peptide synthesizer (Applied Biosystems, foster City, CA). Influenza neuraminidase used in the study was prepared as described previously.…”

Section: Viruses Cells and Reagentsmentioning

confidence: 99%

HA-Pseudotyped Retroviral Vectors for Influenza Antagonist Screening

Wang

Lin

et al. 2009

SLAS Discovery

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Influenza infections are initiated by the binding of the influenza hemagglutinin (hA) and the cellular receptor sialic acids. the binding is followed by internalization, endocytosis, and uncoating to release the influenza genome to the cytoplasm. It is conceivable that specific inhibitors that antagonize any one of these events could prevent the replication of influenza infections. the authors made hA pseudotyped retroviral vectors that express luciferase reporter activities upon transduction to several recipient cells. the transduction of the hA-pseudotype virus particles (hApp) was mediated through the specific interactions between an avian hA and the terminal disaccharides of sialic acid (SA) and galactose (gal) in α-2,3 linkage. the hApp-mediated transduction method was used to develop a high-throughput screening assay and to screen for hits from a fermentation extract library. Specific hits that inhibited the hA-mediated but were noninhibitory to the vesicular stomatitis virus-mediated pseudoviral transductions were identified. A few of these hits have anti-influenza activities that prevent the replication of both h1n1 (WSn) and h5n1 (Rg14) influenza viruses. (Journal of Biomolecular Screening 2009:294-302)

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Inhibition of Influenza Virus Infection by a Novel Antiviral Peptide That Targets Viral Attachment to Cells

Cited by 144 publications

References 36 publications

Multivalent Peptide–Nanoparticle Conjugates for Influenza‐Virus Inhibition

Multivalent Peptide–Nanoparticle Conjugates for Influenza‐Virus Inhibition

Pandemic and seasonal influenza: therapeutic challenges

HA-Pseudotyped Retroviral Vectors for Influenza Antagonist Screening

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