title: 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: Department of Medicine, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, United States.
authors: Gabriel L
authors: GL
authors: Hendricks
authors: Department of Physics, Broida Hall, University of California, Santa Barbara, CA 93106, United States.
authors: Lourdes
authors: L
authors: Velazquez
authors: Department of Medicine, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, United States.
authors: Serena
authors: S
authors: Pham
authors: Department of Medicine, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, United States.
authors: Natasha
authors: N
authors: Qaisar
authors: Department of Biological Engineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02142, United States.
authors: James C
authors: JC
authors: Delaney
authors: Department of Biological Engineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02142, United States.
authors: Karthik
authors: K
authors: Viswanathan
authors: Charles Stark Draper Laboratory, Department of Bioengineering, 555 Technology Square, Cambridge, MA 02139, United States.
authors: Leila
authors: L
authors: Albers
authors: Charles Stark Draper Laboratory, Department of Bioengineering, 555 Technology Square, Cambridge, MA 02139, United States.
authors: James C
authors: JC
authors: Comolli
authors: Department of Biological Engineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02142, United States.
authors: Zachary
authors: Z
authors: Shriver
authors: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, United States.
authors: David M
authors: DM
authors: Knipe
authors: Department of Medicine, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, United States.
authors: Evelyn A
authors: EA
authors: Kurt-Jones
authors: Department of Physics, Broida Hall, University of California, Santa Barbara, CA 93106, United States.
authors: Deborah K
authors: DK
authors: Fygenson
authors: Charles Stark Draper Laboratory, Department of Bioengineering, 555 Technology Square, Cambridge, MA 02139, United States.
authors: Jose M
authors: JM
authors: Trevejo
authors: Department of Medicine, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, United States.
authors: Jennifer P
authors: JP
authors: Wang
authors: Department of Medicine, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, United States.
authors: Robert W
authors: RW
authors: Finberg
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D006497:Heparan Sulfate / Q000008:administration & dosage / Q000494:pharmacology*; D008081:Liposomes; D010224:Parainfluenza Virus 3, Human / Q000187:drug effects* / Q000254:growth & development; D012136:Respiratory Syncytial Viruses / Q000187:drug effects* / Q000254:growth & development; D018139:Simplexvirus / Q000187:drug effects* / Q000254:growth & development; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D006497:Heparan Sulfate; D008081:Liposomes
keywords: Decoy; Heparin; Herpes simplex virus; Liposome; Parainfluenza virus; Respiratory syncytial virus
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