Human immunodeficiency virus type 1 Gag polyprotein capsid-spacer peptide 1 junction (CA-SP1) (CA-SP1)

The Human immunodeficiency virus type 1 (HIV-1) Gag polyprotein capsid-spacer peptide 1 (CA-SP1) junction is a critical structural component involved in the final stages of the viral life cycle (UniProt P04591). During viral budding, the Gag polyprotein is processed by the viral protease into individual functional proteins; the cleavage of the CA-SP1 junction is the final, rate-limiting step in this process (PMID: 33166431). Successful cleavage triggers the structural rearrangement of the viral core into its mature, infectious conical form. This region serves as the primary target for maturation inhibitors (MIs), a class of antiretroviral agents that bind to the CA-SP1 site (PMID: 27153031). By binding here, MIs sterically hinder the HIV-1 protease from accessing the cleavage site, leading to the production of immature, non-infectious virus particles (Wikipedia). This target is particularly significant for developing therapies for treatment-experienced patients who have developed resistance to other classes of antiretroviral drugs. Clinical development of drugs targeting this region must account for significant genetic variability in the SP1 region, which can impact drug susceptibility (NIH).

Other names

Gag CA-SP1 cleavage sitep24-p2 junctionCapsid-spacer peptide 1 junctionHIV-1 Gag maturation site

Maturation inhibition by sterically blocking the HIV-1 protease-mediated cleavage of the Gag polyprotein at the CA-SP1 junction.