Human immunodeficiency virus type 1 nucleocapsid protein (NCp7) (NCp7)

The Human immunodeficiency virus type 1 (HIV-1) nucleocapsid protein (NCp7) is a small, highly basic protein characterized by two highly conserved CCHC-type zinc finger domains [3, 11]. These domains are essential for the protein's role as a nucleic acid chaperone, where they facilitate the packaging of the viral RNA genome into budding virions and assist in reverse transcription by promoting the annealing of tRNA primers and strand transfer [4, 5, 12]. NCp7 is derived from the Gag polyprotein and is critical for both the early and late stages of the viral replication cycle [6, 14]. Because the CCHC motifs are mutationally intolerant, they are considered prime targets for antiretroviral therapy to prevent the emergence of drug resistance [7, 9]. Therapeutic agents known as zinc finger inhibitors or zinc ejectors, such as azodicarbonamide and various benzamide derivatives, act by ejecting the coordinated zinc ion from these domains, thereby inactivating the protein and rendering the virus non-infectious [1, 2, 10]. However, the development of these inhibitors has faced challenges related to their selectivity for viral versus host zinc finger proteins and potential systemic toxicity [9, 10].

Other names

HIV-1 nucleocapsid CCHC zinc finger domainsNCp7NCp7Gag-p7Nucleocapsid proteinp7NC

Zinc ejection from the CCHC motifs through covalent modification of cysteine residues, leading to the disruption of the zinc finger structure, inhibition of viral RNA binding and packaging, and interference with Gag polyprotein processing [1, 2, 14].