PA-1050040

Like protease inhibitors, PA-1050040 and other maturation inhibitors interfere with protease processing of newly translated HIV polyprotein precursor, called gag. This molecule contains a number of HIV proteins in a single polypeptide which is then cleaved by the enzyme protease to produce functional structural proteins. However, unlike the protease inhibitors, PA-1050040 binds the gag protein, not protease. Once bound to gag, PA-1050040 prevents a critical cleavage at a site called the capsid-SP1 junction. The resulting virus particles lack functional capsid protein and have structural defects, rendering them incapable of infecting other cells. For reasons not entirely understood, protease inhibitor-resistant HIV-1 was hypersensitive to PA-1050040 in vitro.