HIV-1 nucleocapsid protein (NCp7)

The HIV-1 nucleocapsid protein (NCp7) is a small, 55-amino acid, highly basic protein that serves as a critical nucleic acid chaperone throughout the viral life cycle [1, 3]. It is characterized by two highly conserved CCHC-type zinc finger motifs that are essential for its function in binding and remodeling viral RNA and DNA [4, 8]. NCp7 is involved in several key processes, including the selective packaging of genomic RNA into budding virions, the dimerization of the viral genome, and the facilitation of reverse transcription by promoting primer annealing and strand transfers [3, 5]. Due to its high degree of sequence conservation across different HIV-1 clades and its essentiality for viral infectivity, NCp7 is considered an attractive target for the development of next-generation antiretroviral therapies, particularly to combat drug-resistant strains [1, 11]. Therapeutic strategies include the use of zinc ejectors, which covalently modify the zinc fingers to cause protein unfolding, and non-covalent inhibitors that block NCp7-nucleic acid interactions [2, 12]. However, challenges such as off-target toxicity and the need for improved potency have limited the clinical advancement of these compounds [1, 11].

Other names

Nucleocapsid protein 7NCp7Gag-NCp7NCNucleocapsid protein p7

Zinc ejection through covalent modification of CCHC zinc finger motifs or non-covalent inhibition of NCp7-nucleic acid interactions.