Researchers at the University of Pennsylvania have determined the structure of an important smallpox virus enzyme and how it binds to DNA. The enzyme called a Topoisomerase is an important drug target for coming up with new ways to fight smallpox
As poxviruses do not take over the genetic machinery inside the nucleus of the host cell they instead encode many of the enzymes they need to replicate their own genes and thus reproduce. Topoisomerase is used by the virus to relieve the excessive twisting of DNA strands that normally occurs during DNA replication and transcription of the viral genes.
Unlike the closely related human enzyme, the viral form only binds to specific DNA sequences. Thus it is more likely to develop inhibitors that are specific to the viral form of the enzyme.
In the case of smallpox virus, the hope is that drugs targeted to the viral topoisomerase will prevent viral replication by stabilizing the broken DNA in the intermediate form, thereby killing the smallpox virus.