Inhibitors of the lipoxygenase pathway specifically block orthopoxvirus replication.

Inhibitors of arachidonic acid metabolism, 5,8,11,14-eicosatetraynoic acid (ETYA), BW755c, and nordihydroguaiaretic acid were found to specifically interfere with the replication of cowpox virus (an orthopoxvirus) both in vivo and in vitro. Further studies in vitro showed that the drugs ETYA and BW755c were effective in inhibiting the replication of two additional orthopoxviruses, ectromelia and vaccinia viruses, but not human parainfluenza virus-3. In ETYA-treated and cowpox virus-infected cells, early and late gene expression were near normal levels, whereas the assembly of virus-specific membranes was severely reduced. These results are compatible with a model of orthopoxvirus replication that has an obligate requirement for arachidonic acid or one of its metabolic forms, possibly in the assembly of virus-specific membranes.