HIV-1 integrase strand transfer enzyme (HIV-1 IN)

HIV-1 integrase strand transfer enzyme is a multidomain retroviral enzyme essential for the integration of HIV-1's viral DNA into the host cell genome—a pivotal step for viral replication. The enzyme comprises three structural domains: N-terminal (zinc-binding), central catalytic core (featuring a DDE motif), and C-terminal (DNA-binding), and mediates two reactions: 3′ end processing and strand transfer. It is a prime therapeutic target with several approved drugs known as integrase strand transfer inhibitors (INSTIs). These drugs inhibit strand transfer, disrupting viral propagation and have become central to HIV treatment regimens, although resistance can occur, especially with first-generation inhibitors like raltegravir and elvitegravir, while newer drugs such as dolutegravir and bictegravir are more resilient against resistance. The absence of an equivalent enzyme in human cells enables selective targeting with minimal off-target effects.

Other names

HIV-1 integraseHuman immunodeficiency virus type 1 integraseHIV integraseIN

Inhibition of strand transfer activity, preventing integration of viral DNA into host genome; Chelation of Mg(2+) ions in the enzyme active site, disrupting catalytic function