Figure 1

Strand transfer reaction and proposed mechanism of IN inhibition by INSTIs adapted from (53). A) A trans-esterification reaction involving a nucleophilic attack on the 3' hydroxyl group of the two newly processed 3' viral DNA ends on the phosphodiester backbone of the host DNA. The host DNA and viral DNA are shown in blue and red, respectively; the yellow arrow indicates the scissile phosphodiester. B) IN strand transfer inhibitors may chelate the two metal ions in the catalytic site, thereby blocking the binding of host DNA.