Prevention of Influenza Pneumonitis by Sialic Acid–Conjugated Dendritic Polymers

Abstract

Influenza A viral infection begins by hemagglutinin glycoproteins on the viral envelope binding to cell membrane sialic acid (SA). Free SA monomers cannot block hemagglutinin adhesion in vivo because of toxicity. Polyvalent, generation 4 (G4) SA-conjugated polyamidoamine (PAMAM) dendrimer (G4-SA) was evaluated as a means of preventing adhesion of 3 influenza A subtypes (H1N1, H2N2, and H3N2). In hemagglutination-inhibition assays, G4-SA was found to inhibit all H3N2 and 3 of 5 H1N1 influenza subtype strains at concentrations 32-170 times lower than those of SA monomers. In contrast, G4-SA had no ability to inhibit hemagglutination with H2N2 subtypes or 2 of 5 H1N1 subtype strains. In vivo experiments showed that G4-SA completely prevented infection by a H3N2 subtype in a murine influenza pneumonitis model but was not effective in preventing pneumonitis caused by an H2N2 subtype. Polyvalent binding inhibitors have potential as antiviral therapeutics, but issues related to strain specificity must be resolved.

Development of photocrosslinked sialic acid containing polymers for use in Aβ toxicity attenuation

“…Others have developed multivalent sialic acid polymers by conjugating sialic acid to a dendrimer backbone for prevention of viral adhesion and infection that were effective both in vitro and in vivo [34,35]. However, when we have previously used sialic acid modified dendrimers to attenuate Aβ toxicity in cell culture models using neuroblastoma cells, dendrimer backbone toxicity was evident at concentrations between 3 and 80 µM dendrimer, depending upon the dendrimer concentration [1,36].…”

MannosylGlycodendritic Structure Inhibits DC-SIGN-Mediated Ebola VirusInfection in cis and in trans

“…The low affinity of carbohydrate interactions, compensated for in nature by the multivalent presentation of carbohydrate units, has encouraged the design of carbohydrate multivalent structures to interfere with biological processes in which carbohydrates are involved. Among these multivalent systems, glycodendrimers are one of the most popular systems (4), and they have been used previously in several processes, including blockage of viral receptors (13,15). Previous works with glycodendritic structures, based on the hyperbranched polymer BoltornH30 (Perstorp Specialty Chemicals), have shown a number of advantages, including low cytotoxicity, high solubility in physiological media, and relatively low cost (2).…”

Nanotechnology developments: opportunities for animal health and production

“…Such glycodendrimers have also been used to trap and deactivate some strains of influenza virus particles. 37 There are ongoing attempts to build micro-electromechanical system (MEMS)-based microrobots intended for in vivo use. Cytobots and karyobots for performing wireless intracellular surgery, artificial mechanical red blood cells or respirocytes, and white cells called microbivores are all under development.…”