title: Contortrostatin, a homodimeric disintegrin isolated from snake venom inhibits herpes simplex virus entry and cell fusion.
abstract: BACKGROUND
  Herpes simplex virus (HSV) causes significant health problems from periodical skin and corneal lesions to encephalitis. HSV entry provides a unique opportunity for therapeutic intervention. In this study, we evaluated contortrostatin (CN), an Arg-Gly-Asp motif containing disintegrin isolated from snake venom, as a novel therapeutic agent with ability to block HSV entry and related membrane fusion.
  
  
  METHODS
  In vitro efficacy of CN against HSV was determined using an HSV type-1 (HSV-1) entry assay based on the measurement of β-galactosidase reporter activity originating from the genome of a recombinant strain of HSV-1(KOS) gL86. HSV-1 glycoprotein-mediated cell-to-cell fusion was used to study the effect of CN on polykaryocyte formation. Primary as well as transformed cell lines were used for this study.
  
  
  RESULTS
  Pre-treatment of Chinese hamster ovary (CHO-K1) cells expressing HSV-1 glycoprotein D receptors and primary cultures of human corneal fibroblasts (CF) with CN resulted in the inhibition of entry, cell-to-cell fusion, and polykaryocyte formation. Interestingly, a more pronounced anti-HSV-1 effect was observed in naturally susceptible CF than CHO-K1 cells.
  
  
  CONCLUSIONS
  CN, a novel venom-derived peptide, exhibits the ability to block two key steps, entry and cell-to-cell fusion, in HSV infection. Showing strong promise for development as an anti-HSV agent, it also demonstrates better prophylactic efficacy in primary cells.
authors.affiliation: Department of Basic Medical Sciences, Western University of Health Sciences, Pomona, CA, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Hubbard
authors.forename: Samiksha
authors.initials: S
authors.lastname: Choudhary
authors.forename: Erika
authors.initials: E
authors.lastname: Maus
authors.forename: Deepak
authors.initials: D
authors.lastname: Shukla
authors.forename: Stephen
authors.initials: S
authors.lastname: Swenson
authors.forename: Francis S
authors.initials: FS
authors.lastname: Markland
authors.forename: Vaibhav
authors.initials: V
authors.lastname: Tiwari
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology; D016466:CHO Cells; D002459:Cell Fusion; D003315:Cornea / Q000166:cytology; D006224:Cricetinae; D019483:Disintegrins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D005347:Fibroblasts / Q000187:drug effects / Q000821:virology; D015726:Giant Cells / Q000737:chemistry / Q000187:drug effects; D006367:HeLa Cells; D006561:Herpes Simplex / Q000821:virology; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000472:pathogenicity; D054884:Host-Pathogen Interactions; D006801:Humans; D061251:Primary Cell Culture; D011956:Receptors, Cell Surface / Q000737:chemistry; D012910:Snake Venoms / Q000737:chemistry*; D014162:Transfection; D014759:Viral Envelope Proteins / Q000737:chemistry; D010948:Viral Plaque Assay; D053586:Virus Internalization / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D019483:Disintegrins; D011956:Receptors, Cell Surface; D012910:Snake Venoms; D014759:Viral Envelope Proteins; C403494:contortrostatin; C039447:glycoprotein D, Human herpesvirus 1