HIV protease is a homodimeric aspartyl protease. It is worth noting that, HIV protease is crucial for the viral life-cycle. Specifically, HIV protease cleaves proviral polyproteins, hence creates mature protein components required for the formation of an infectious virus. Furthermore, HIV protease cleaves newly synthesized polyproteins at the appropriate places to create the mature protein components of an infectious HIV virion. In a word, HIV protease is a critical target in designing anti-retroviral agents to treat HIV/AIDS (acquired immune deficiency syndrome). Meanwhile, most of the strains of HIV infected in the world are HIV-1, with group M being the most common.

Here, we focus on the HIV-1 protease inhibitor, Nelfinavir (AG-1341).

Nelfinavir is an orally active HIV-1 protease inhibitor. Specifically, Nelfinavir is a potent and orally bioavailable HIV-1 protease inhibitor. The Ki value of Nelfinavir is 2 nM for HIV infection. Especially, Nelfinavir is a broad-spectrum, anticancer agent. In vitro, Nelfinavir inhibits the proliferation of multiple myeloma cells. Moreover, Nelfinavir inhibits 26S chymotrypsin-like proteasome activity, impairs proliferation and triggers apoptosis of the myeloma cell lines and fresh plasma cells. That is to say, Nelfinavir activates the cleavage of caspase-3, decreases the phosphorylation of AKT, STAT-3, ERK1/2, and activates the pro-apoptotic pathway of the unfolded protein response system. Extraordinary, Nelfinavir is also a SARS-CoV 3CL^pro inhibitor with an IC₅₀ of 35.93 μM. In vivo, Nelfinavir decreases multiple myeloma cell growth in NOD/SCID mice.

Taken together, Nelfinavir is an orally active HIV-1 protease inhibitor. Nelfinavir is a potent compound of immune and cancer disease.

References:

[1]. Gills JJ, et al. Clin Cancer Res. 2007 Sep; 13(17):5183-5194.