Multivalent Peptide–Nanoparticle Conjugates for Influenza‐Virus Inhibition

Abstract

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.

Bioinspired Artificial Nanodecoys for Hepatitis B Virus

“…[6] It is clear that MVs engineered with highly stable "mimics" of receptor via agenetic modification procedure has the potential to address the limitations of receptor-mediated antiviral treatment with good specificity and safety profiles. [7] Human sodium taurocholate co-transporting polypeptide (hNTCP) is an ine-transmembrane transporter consisting of 349 amino acids with amolecular mass of 56 kD.hNTCP has been demonstrated as af unctional receptor of HBV and features essential high binding affinity for HBVpreS protein. [8] We thus hypothesized that MVs from NTCP-reconstituted cells with hNTCP overexpressed on the cell membrane could be an effective means of bestowing binding specificity towards HBV,w hich would lead to ar eceptormediated antiviral effect.…”

“…[6] It is clear that MVs engineered with highly stable “mimics” of receptor via a genetic modification procedure has the potential to address the limitations of receptor-mediated antiviral treatment with good specificity and safety profiles. [7] …”

Specific Decoration of a Discrete Bismuth Oxido Cluster by Selected Peptides towards the Design of Metal Tags

“…The arrangement of the side‐chains in case of two adjacent glutamic acids is most likely unfavorable for simultaneous complexation within a single cluster. Larger distances between binding residues, however, offer more confirmative flexibility to adapt to the binding geometry required and probably enable multivalent effects . Furthermore, for strong and weak binders, peptide sequences were identified bearing only a single glutamic acid, indicating that not only carboxylic interactions contribute to the binding, but the whole peptide sequence.…”

Inhibitory activity of selenium nanoparticles functionalized with oseltamivir on H1N1 influenza virus

“…[6][7][8] Hemagglutinin (HA) plays an important role in viral infection by combining sialic acid-containing receptors on host cells and mediating the entry and fusion of the virus. 9,10 Neuraminidase (NA) and HA are the most significant glycoproteins on the surface of the influenza virus. 11,12 NA plays an important role in assisting the virus cleave the linkage between sialic acid and HA, when mature viruses separate from the host cell surface.…”