Heparin octasaccharide decoy liposomes inhibit replication of multiple viruses.

Abstract:

:Heparan sulfate (HS) is a ubiquitous glycosaminoglycan that serves as a cellular attachment site for a number of significant human pathogens, including respiratory syncytial virus (RSV), human parainfluenza virus 3 (hPIV3), and herpes simplex virus (HSV). Decoy receptors can target pathogens by binding to the receptor pocket on viral attachment proteins, acting as 'molecular sinks' and preventing the pathogen from binding to susceptible host cells. Decoy receptors functionalized with HS could bind to pathogens and prevent infection, so we generated decoy liposomes displaying HS-octasaccharide (HS-octa). These decoy liposomes significantly inhibited RSV, hPIV3, and HSV infectivity in vitro to a greater degree than the original HS-octa building block. The degree of inhibition correlated with the density of HS-octa displayed on the liposome surface. Decoy liposomes with HS-octa inhibited infection of viruses to a greater extent than either full-length heparin or HS-octa alone. Decoy liposomes were effective when added prior to infection or following the initial infection of cells in vitro. By targeting the well-conserved receptor-binding sites of HS-binding viruses, decoy liposomes functionalized with HS-octa are a promising therapeutic antiviral agent and illustrate the utility of the liposome delivery platform.

journal_name

Antiviral Res

journal_title

Antiviral research

authors

Hendricks GL,Velazquez L,Pham S,Qaisar N,Delaney JC,Viswanathan K,Albers L,Comolli JC,Shriver Z,Knipe DM,Kurt-Jones EA,Fygenson DK,Trevejo JM,Wang JP,Finberg RW

doi

10.1016/j.antiviral.2015.01.008

subject

Has Abstract

pub_date

2015-04-01 00:00:00

pages

34-44

eissn

0166-3542

issn

1872-9096

pii

S0166-3542(15)00009-1

journal_volume

116

pub_type

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