Human immunodeficiency virus type 1 protease (HIV-1 PR) (HIV-1 PR)

HIV-1 protease is an essential enzyme produced by the Human Immunodeficiency Virus type 1 (HIV-1) that plays a critical role in the viral life cycle [1, 5]. It is an aspartic protease responsible for the post-translational cleavage of the Gag and Gag-Pol polyproteins into functional mature proteins, such as reverse transcriptase, integrase, and the structural proteins of the viral capsid [1, 4]. This process, known as viral maturation, is necessary for the production of infectious progeny virions [5]. Without functional protease activity, HIV particles remain immature and non-infectious [4]. Consequently, HIV-1 protease is a primary therapeutic target in the treatment of HIV/AIDS [3]. Drugs targeting this enzyme, known as protease inhibitors (PIs), bind to its active site and prevent the cleavage of polyproteins, thereby halting viral replication [2, 4]. While highly effective, the use of PIs is often associated with significant metabolic side effects and requires careful management of drug-drug interactions, particularly because some PIs like ritonavir are also potent inhibitors of the cytochrome P450 system [2, 4].

Other names

HIV-1 retropepsinHIV-1 aspartyl proteaseHIV-1 proteasePRHIV-1 protease – ritonavir

Competitive inhibition of the protease active site, preventing the cleavage of Gag and Gag-Pol polyproteins into mature functional proteins, which leads to the production of non-infectious immature virions.