title: Synthesis of cellulose nanocrystals carrying tyrosine sulfate mimetic ligands and inhibition of alphavirus infection.
abstract: We present two facile approaches for introducing multivalent displays of tyrosine sulfate mimetic ligands on the surface of cellulose nanocrystals (CNCs) for application as viral inhibitors. We tested the efficacy of cellulose nanocrystals, prepared either from cotton fibers or Whatman filter paper, to inhibit alphavirus infectivity in Vero (B) cells. Cellulose nanocrystals were produced by sulfuric acid hydrolysis leading to nanocrystal surfaces decorated with anionic sulfate groups. When the fluorescent marker expressing Semliki Forest virus vector, VA7-EGFP, was incubated with CNCs, strong inhibition of virus infectivity was achieved, up to 100 and 88% for cotton and Whatman CNCs, respectively. When surface sulfate groups of CNCs were exchanged for tyrosine sulfate mimetic groups (i.e. phenyl sulfonates), improved viral inhibition was attained. Our observations suggest that the conjugation of target-specific functionalities to CNC surfaces provides a means to control their antiviral activity. Multivalent CNCs did not cause observable in vitro cytotoxicity to Vero (B) cells or human corneal epithelial (HCE-T) cells, even within the 100% virus-inhibitory concentrations. Based on the similar chemistry of known polyanionic inhibitors, our results suggest the potential application of CNCs as inhibitors of other viruses, such as human immunodeficiency virus (HIV) and herpes simplex viruses.
authors.affiliation: Polymer Technology, Department of Biotechnology and Chemical Technology, Aalto University School of Chemical Technology , P.O. Box 16100, 00076 Aalto, Finland.
authors.forename: Justin O
authors.initials: JO
authors.lastname: Zoppe
authors.forename: Ville
authors.initials: V
authors.lastname: Ruottinen
authors.forename: Janne
authors.initials: J
authors.lastname: Ruotsalainen
authors.forename: Seppo
authors.initials: S
authors.lastname: Rönkkö
authors.forename: Leena-Sisko
authors.initials: LS
authors.lastname: Johansson
authors.forename: Ari
authors.initials: A
authors.lastname: Hinkkanen
authors.forename: Kristiina
authors.initials: K
authors.lastname: Järvinen
authors.forename: Jukka
authors.initials: J
authors.lastname: Seppälä
mesh_terms: D018354:Alphavirus Infections / Q000188:drug therapy*; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D032701:Biomimetics; D002482:Cellulose / Q000138:chemical synthesis* / Q000737:chemistry; D002522:Chlorocebus aethiops; D019573:Epithelium, Corneal / Q000166:cytology / Q000187:drug effects; D018773:Genes, erbB-1; D008024:Ligands; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D036103:Nanotechnology / Q000379:methods*; D012672:Semliki forest virus / Q000187:drug effects* / Q000235:genetics; D017550:Spectroscopy, Fourier Transform Infrared; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000737:chemistry; D014709:Vero Cells / Q000187:drug effects / Q000821:virology
chemical_list: D000998:Antiviral Agents; D008024:Ligands; C005662:tyrosine O-sulfate; D014443:Tyrosine; D002482:Cellulose