| Summary: | <p>Abstract</p> <p>Background</p> <p>The EB peptide is a 20-mer that was previously shown to have broad spectrum <it>in vitro </it>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 <it>in vitro </it>activity against the zoonotic orthopoxviruses cowpox and monkeypox and for <it>in vivo </it>activity in mice against vaccinia and cowpox.</p> <p>Findings</p> <p>In yield reduction assays, EB had an EC<sub>50 </sub>of 26.7 μM against cowpox and 4.4 μM against monkeypox. The EC<sub>50 </sub>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 <it>in vitro </it>by disrupting virus entry, as evidenced by a reduction of the release of virus cores into the cytoplasm. Monkeypox was also inhibited <it>in vitro </it>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 <it>in vivo </it>activity against cowpox in mice.</p> <p>Conclusions</p> <p>While EB did demonstrate some <it>in vivo </it>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 <it>in vitro </it>than as a therapeutic against orthopoxviruses <it>in vivo</it>.</p>
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