Capsid protein–SP1 cleavage site (CA–SP1 cleavage site)

The **capsid protein–SP1 cleavage site** is a specific proteolytic junction within the HIV-1 Gag polyprotein, located between the C-terminal domain (CTD) of the capsid (CA) protein and the SP1 (spacer peptide 1) segment[1][3][5][7]. This site is one of several cleaved by the viral protease during HIV-1 maturation. Cleavage at this site is structurally sequestered within a six-helix bundle formed by residues from CA and SP1 in the immature HIV-1 Gag lattice, making it the most delayed and rate-limiting cleavage event during maturation[1][5][7]. Proper processing here is essential for the structural rearrangements that convert the virus particle from an immature to a mature, infectious state[2][4][5]. Inhibiting this cleavage (for example, with the drug bevirimat) disrupts viral maturation and abrogates infectivity, making the CA–SP1 cleavage site a validated therapeutic target for HIV-1 infection[5][6]. Importantly, resistance mutations can emerge at this site, affecting drug efficacy[5]. No known host protein counterparts exist, which makes it a highly specific antiviral target.

Other names

CA–SP1 junctionCapsid–SP1 junctionGag CA–SP1 siteC-terminal CA–SP1 cleavage site

Inhibition of proteolytic cleavage at the CA–SP1 site blocks the final stage of HIV-1 maturation, leading to noninfectious viral particles[5][6].