Scientists have identified a unique DNA-copying protein in African swine fever virus (ASFV) that may offer a target for drugs designed to combat the lethal disease.
The discovery is reported in a study published in PLOS Biology by Yiqing Chen and colleagues at Fudan University in Shanghai, China.
ASFV is a highly contagious and deadly disease in pigs that has spread from Africa to areas of Europe and Asia.
No treatments are available and control relies on killing entire herds once infection is detected.
Viral replication depends, in part, on a polymerase enzyme, AsfvPolX, that repairs breaks in the DNA, but the structure of this enzyme has not been determined in detail.
The authors used x-ray diffraction and nuclear magnetic resonance to solve the structure at atomic resolution.
Unique binding pocket
The team found the enzyme contained a unique binding pocket for the building blocks of DNA (nucleotides) not seen in related enzymes in other organisms.
They also found several other unique structural features, including a pair of hydrophobic amino acids that interact with incoming nucleotides and a “platform” created by two basic amino acids that stabilises a mismatched nucleotide pair, increasing the rate of incorporation of erroneous nucleotides into the DNA chain during the repair process.
Together, these features give the polymerase its unique character of a high rate of DNA replication combined with a high copying error rate.
As a result, the authors suggest blocking the binding pocket with a drug may be a valuable strategy to treat ASFV infection.
“Exploiting this unique structural feature to attack the virus may offer a rapid route to develop treatments for this important agricultural virus,” said Chen.
However, he noted one caveat; the high error rate of the AsfvPolX polymerase enzyme means the virus mutates rapidly and may evolve resistance to drugs designed to block it.
- For full details, read “Unique 5′-P recognition and basis for dG:dGTP misincorporation of ASFV DNA polymerase X“.