Despite the eradication in 1979 of the smallpox virus, the most devastating virus in the poxvirus family, these viruses still present a risk of reemergence, whether through bioterrorism or introduction from an animal reservoir.

Researchers from the IBS, in collaboration with scientists from the Armed Forces Biomedical Research Institute, have determined the crystallographic structure of the DNA polymerase E9 of the vaccinia virus at a resolution of 2.7 Å. This is an important antiviral target since it is 98% identical to the smallpox virus.

Using a combination of approaches such as the sensitivity of peptides to hydrogen-deuterium exchange by mass spectrometry and the effect of mutations analyzed by surface plasmon resonance, the scientists located the site of interaction with the co-factor A20/D4. The detailed knowledge of the interfaces between the different subunits could be used to design inhibitors that interfere with the assembly of the complex, just as the high-resolution structure makes it possible to understand the mechanisms of antivirals and resistance mutations.