Antiviral activity of the EB peptide against zoonotic poxviruses.
BACKGROUND
The EB peptide is a 20-mer that was previously shown to have broad spectrum in vitro activity against several unrelated viruses, including highly pathogenic avian influenza, herpes simplex virus type I, and vaccinia, the prototypic orthopoxvirus. To expand on this work, we evaluated EB for in vitro activity against the zoonotic orthopoxviruses cowpox and monkeypox and for in vivo activity in mice against vaccinia and cowpox.


RESULTS
In yield reduction assays, EB had an EC50 of 26.7 μM against cowpox and 4.4 μM against monkeypox. The EC50 for plaque reduction was 26.3 μM against cowpox and 48.6 μM against monkeypox. A scrambled peptide had no inhibitory activity against either virus. EB inhibited cowpox in vitro by disrupting virus entry, as evidenced by a reduction of the release of virus cores into the cytoplasm. Monkeypox was also inhibited in vitro by EB, but at the attachment stage of infection. EB showed protective activity in mice infected intranasally with vaccinia when co-administered with the virus, but had no effect when administered prophylactically one day prior to infection or therapeutically one day post-infection. EB had no in vivo activity against cowpox in mice.


CONCLUSIONS
While EB did demonstrate some in vivo efficacy against vaccinia in mice, the limited conditions under which it was effective against vaccinia and lack of activity against cowpox suggest EB may be more useful for studying orthopoxvirus entry and attachment in vitro than as a therapeutic against orthopoxviruses in vivo.
Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. altmannse@niaid.nih.gov
Sharon E
SE
Altmann
Curtis R
CR
Brandt
Peter B
PB
Jahrling
Joseph E
JE
Blaney
D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015605:Cowpox / Q000188:drug therapy*; D015608:Cowpox virus / Q000187:drug effects*; D004195:Disease Models, Animal; D004481:Ectromelia virus / Q000187:drug effects*; D051519:Fibroblast Growth Factor 4 / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008826:Microbial Sensitivity Tests; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D016019:Survival Analysis; D016896:Treatment Outcome; D014615:Vaccinia / Q000188:drug therapy*; D019562:Viral Load; D010948:Viral Plaque Assay; D053585:Virus Attachment / Q000187:drug effects; D053586:Virus Internalization / Q000187:drug effects
D000998:Antiviral Agents; C496445:FGF4 protein, human; D051519:Fibroblast Growth Factor 4; D009842:Oligopeptides