title: Abalone Hemocyanin Blocks the Entry of Herpes Simplex Virus 1 into Cells: a Potential New Antiviral Strategy.
abstract: A marine-derived compound, abalone hemocyanin, from Haliotis rubra was shown to have a unique mechanism of antiviral activity against herpes simplex virus 1 (HSV-1) infections. In vitro assays demonstrated the dose-dependent and inhibitory effect of purified hemocyanin against HSV-1 infection in Vero cells with a 50% effective dose (ED50) of 40 to 50 nM and no significant toxicity. In addition, hemocyanin specifically inhibited viral attachment and entry by binding selectively to the viral surface glycoproteins gD, gB, and gC, probably by mimicking their receptors. However, hemocyanin had no effect on postentry events and did not block infection by binding to cellular receptors for HSV. By the use of different mutants of gD and gB and a competitive heparin binding assay, both protein charge and conformation were shown to be the driving forces of the interaction between hemocyanin and viral glycoproteins. These findings also suggested that hemocyanin may have different motifs for binding to each of the viral glycoproteins B and D. The dimer subunit of hemocyanin with a 10-fold-smaller molecular mass exhibited similar binding to viral surface glycoproteins, showing that the observed inhibition did not require the entire multimer. Therefore, a small hemocyanin analogue could serve as a new antiviral candidate for HSV infections.
authors.affiliation: School of Chemical and Biomolecular Engineering, The University of Sydney, New South Wales, Australia.
authors.forename: Negar
authors.initials: N
authors.lastname: Talaei Zanjani
authors.affiliation: Centre for Virus Research, The Westmead Institute for Medical Research, The University of Sydney, Westmead, New South Wales, Australia.
authors.forename: Monica
authors.initials: M
authors.lastname: Miranda-Saksena
authors.affiliation: School of Chemical and Biomolecular Engineering, The University of Sydney, New South Wales, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Valtchev
authors.affiliation: Centre for Virus Research, The Westmead Institute for Medical Research, The University of Sydney, Westmead, New South Wales, Australia.
authors.forename: Russell J
authors.identifier: http://orcid.org/0000-0002-8433-4336
authors.initials: RJ
authors.lastname: Diefenbach
authors.affiliation: Arbovirus Emerging Diseases Unit, Centre for Infectious Diseases and Microbiology Laboratory Services, Pathology West-ICPMR Westmead, New South Wales, Australia.
authors.forename: Linda
authors.initials: L
authors.lastname: Hueston
authors.affiliation: Protein Core Facility, The Westmead Institute for Medical Research, The University of Sydney, Westmead, New South Wales, Australia.
authors.forename: Eve
authors.initials: E
authors.lastname: Diefenbach
authors.affiliation: School of Chemical and Biomolecular Engineering, The University of Sydney, New South Wales, Australia.
authors.forename: Fareed
authors.initials: F
authors.lastname: Sairi
authors.affiliation: School of Chemical and Biomolecular Engineering, The University of Sydney, New South Wales, Australia.
authors.forename: Vincent G
authors.initials: VG
authors.lastname: Gomes
authors.affiliation: Centre for Virus Research, The Westmead Institute for Medical Research, The University of Sydney, Westmead, New South Wales, Australia tony.cunningham@sydney.edu.au fariba.dehghani@sydney.edu.au.
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Cunningham
authors.affiliation: School of Chemical and Biomolecular Engineering, The University of Sydney, New South Wales, Australia tony.cunningham@sydney.edu.au fariba.dehghani@sydney.edu.au.
authors.forename: Fariba
authors.initials: F
authors.lastname: Dehghani
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001665:Binding Sites; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D049851:Gastropoda / Q000737:chemistry; D006023:Glycoproteins / Q000378:metabolism; D006433:Hemocyanins / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000378:metabolism / Q000472:pathogenicity; D014709:Vero Cells / Q000187:drug effects / Q000821:virology
chemical_list: D000998:Antiviral Agents; D006023:Glycoproteins; D006433:Hemocyanins