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Capsid protein-SP1 cleavage site (CA-SP1 site)
- Target
- CA-SP1 site
- Molecular classification
- Cleavage site, Protein-protein junction within Gag polyprotein, Viral structural determinant, Other (not a receptor, enzyme, transporter, or traditional drug target protein)
01
Overview
The Capsid protein-SP1 cleavage site is a highly conserved junction within the HIV-1 Gag polyprotein that links the capsid (CA) domain and the SP1 spacer peptide. During virus maturation, the viral protease cleaves this site last, triggering major structural changes that enable the native, infectious capsid lattice to form. The CA-SP1 junction is sequestered within a six-helix bundle in the immature virion lattice, making its proteolysis rate-limited by structural unfolding, a key step that can be disrupted by small-molecule maturation inhibitors such as bevirimat. Mutations at or near the CA-SP1 site can affect drug susceptibility and virus maturation, making this sequence a focus of antiviral drug development targeting new mechanisms distinct from earlier HIV therapies.
- Other names
- CA-SP1 junctionCA-SP1 boundaryHIV-1 Gag CA-SP1 cleavage site
02
Mechanism of action
Inhibition of proteolytic cleavage at the CA-SP1 site prevents proper capsid formation and blocks production of infectious virus particles.
03
Biological functions
Structural rearrangement during viral maturationRegulation of proteolytic maturationAssembly of the viral capsid lattice
04
Disease associations
Infection (HIV-1)
05
Safety considerations
Viral resistance via mutations in SP1 or surrounding Gag regionsPotential for incomplete viral inhibition if suboptimal targeting or drug resistance mechanisms emerge
06
Interacting drugs
Bevirimat (BVM) (prototype HIV maturation inhibitor)
1 more in the full profile.
07
Biomarkers
Mutations in CA-SP1, e.g., SP1-A1V, SP1-V7A, can confer resistance or susceptibility to maturation inhibitorsProcessing intermediate accumulation (measured in virus particles)
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