HIV protease and its inhibition

The HIV protease (HPR) is a virus-specific aspartic protease responsible for processing the polyproteins of gag and gag-pol during virion maturation and for the proliferation of HIV. The activity of HPR is essential for virus infectivity, thus it is an important target for the development of anti-HIV drugs. HPR is only one major viral protease, since there are other proteases, which are specific to HCV or SARS-CoV-2 and are therapeutic targets as well. HPR inhibitors in combination with other classes of anti-HIV drugs are one of the main components of an effective anti-HIV therapy. Nevertheless, upon several circumstances, HIV can develop a discrete pattern of resistance towards one or several HPR inhibitors through the phenomenon of cross-resistance. The aim of our work is to illustrate various features of HPR: its structure, the various mechanisms which lead to its inhibition, the HPR inhibitors which are used in the clinical arena, and the pathways involved in drug resistance, plus the mechanisms to overcome it.