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.

• Authors: Gabriel L Hendricks, Lourdes Velazquez, Serena Pham, Natasha Qaisar, James C Delaney, Karthik Viswanathan, Leila Albers, James C Comolli, Zachary Shriver, David M Knipe, Evelyn A Kurt-Jones, Deborah K Fygenson, Jose M Trevejo, Jennifer P Wang, Robert W Finberg
• Journal: Antiviral research (Antiviral Res) Vol. 116 Pg. 34-44 (Apr 2015) ISSN: 1872-9096 [Electronic] Netherlands
• PMID: 25637710 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Antiviral Agents
• Liposomes
• Heparitin Sulfate

Topics

• Animals
• Antiviral Agents (administration & dosage, chemistry, pharmacology)
• Heparitin Sulfate (administration & dosage, pharmacology)
• Liposomes
• Parainfluenza Virus 3, Human (drug effects, growth & development)
• Respiratory Syncytial Viruses (drug effects, growth & development)
• Simplexvirus (drug effects, growth & development)
• Vero Cells
• Virus Replication (drug effects)