Keele Research Repository

The re-emergence of poxviral zoonotic infections and the threat of bioterrorism emphasise the demand
for efective antipoxvirus therapies. Here, we show that carbenoxolone, a pharmacological inhibitor of
gap junction function and a compound widely used in cell culture, is capable of hindering the replication
of Vaccinia virus, the prototypical poxvirus, in a gap junction-independent manner in a human
keratinocyte cell line. Viral protein synthesis occurs in the presence of carbenoxolone but infectious
virion formation is minimal, indicating that carbenoxolone blocks viral morphogenesis. Initial viability
tests suggested that carbenoxolone was not toxic to cells. However, electron microscopic analysis of
carbenoxolone treated cells revealed that it alters the cellular endomembrane system. This widespread
ultrastructural damage prevents Vaccinia virus virion assembly. These results strengthen the need for
thorough characterisation of the effects of antiviral compounds on the cellular ultrastructure.