The threat of smallpox virus as a bioterrorist weapon is raising international concerns again since the
anthrax attacks in the USA in 2001. The medical readiness of treating patients suffering from such
infections is a prerequisite of an effective civil defense system. Currently the only therapeutic option for the treatment of
poxvirus infections relies on the virostatic nulceosid analog
cidofovir, although severe side effects and
drug resistant strains have been described. A growing understanding of poxvirus pathogenesis raises the possibility to explore other appropriate targets involved in the viral replication cycle. Poxvirus encoded
growth factors such as the
Vaccinia Growth Factor (VGF) stimulate host cells via the
Epidermal Growth Factor Receptor (EGFR) and thereby facilitate viral spreading. In this study we could visualize for the first time the paracrine priming of uninfected cells for subsequent
infection by orthopoxviruses directly linked to EGFR phosphorylation. Since EGFR is a well known target for anti-
tumor therapy small molecules for inhibition of its
tyrosine kinase (TK) activity are readily available and clinically evaluated. In this study we analyzed three different EGFR
receptor tyrosine kinase inhibitors for inhibition of
orthopoxvirus infection in epithelial cells. The inhibitor shown to be most effective was
Gefitinib (
Iressa) which is already approved as a
drug for anti-
tumor medication in the USA and in Europe. Thus Gefitnib may provide a new therapeutic option for single or combination
therapy of acute
poxvirus infections, acting on a cellular target and thus reducing the risk of viral resistance to treatment.