HIV-1 integrase (IN)

HIV-1 integrase is a 32 kDa enzyme encoded by the pol gene of the Human Immunodeficiency Virus type 1 (HIV-1) (UniProt P03366). It is essential for viral replication as it catalyzes the integration of the reverse-transcribed viral DNA into the host cell's chromosomal DNA (PubMed: 28803253). This process occurs in two main stages: 3'-processing, where two nucleotides are removed from the viral DNA ends, and strand transfer, where the viral DNA is covalently joined to the host DNA (StatPearls: NBK470561). Because there is no human counterpart to this enzyme, it serves as an ideal target for highly specific antiretroviral drugs. Integrase strand transfer inhibitors (INSTIs), such as dolutegravir and bictegravir, are the primary class of drugs targeting this enzyme, effectively blocking the strand transfer step and preventing the establishment of a provirus (PubMed: 30124164). By halting the integration process, these drugs prevent the virus from hijacking the host's cellular machinery for further replication.

Other names

Integrasep31Pol proteinRetroviral integraseHIV-1 IN

Integrase strand transfer inhibitors (INSTIs) bind to the active site of the integrase enzyme when it is in complex with viral DNA (the intasome), specifically chelating the magnesium cofactors required for the strand transfer reaction, thereby preventing the insertion of viral DNA into the host genome (StatPearls: NBK470561).