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The HIV-1 Group-specific antigen (Gag) polyprotein is the essential structural precursor required for the assembly, budding, and release of infectious HIV-1 particles. Synthesized as a 55 kDa precursor (Pr55Gag), it is later cleaved by the viral protease into functional subunits: matrix (MA/p17), capsid (CA/p24), nucleocapsid (NC/p7), and p6, plus two spacer peptides (SP1 and SP2) (UniProt P04591). Gag orchestrates the transport of viral components to the plasma membrane and the packaging of the viral RNA genome (PubMed: 22301554). In Clade C, the most prevalent HIV-1 subtype globally, consensus sequences of Gag are frequently used in vaccine design to elicit broad T-cell mediated immune responses (PubMed: 17601810). Pharmacological targeting of Gag includes capsid inhibitors like Lenacapavir, which interfere with multiple stages of the viral life cycle, and maturation inhibitors that block the final processing steps required for virion infectivity (NIH: ClinicalInfo).
Capsid inhibition (disrupting assembly and disassembly) and maturation inhibition (preventing the cleavage of the CA-SP1 junction by viral protease).
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