HIV-1 nucleocapsid protein (NCp7) (NCp7)

The HIV-1 nucleocapsid protein (NCp7) is a small, basic protein containing two highly conserved CCHC-type zinc finger domains, often referred to as zinc knuckles (NIH, 2018). These domains are critical for the virus's life cycle, performing essential roles in the selection and packaging of genomic RNA into budding virions and acting as a nucleic acid chaperone to facilitate reverse transcription (Wikipedia, 2024; NIH, 2018). Because the CCHC motifs are invariant across nearly all retroviruses and are highly resistant to mutations that would preserve function, they represent an attractive therapeutic target (Grantome, 2024). Drugs targeting these domains, known as zinc finger inhibitors or zinc ejectors, work by covalently modifying the cysteine residues that coordinate the zinc ion, causing the ion's release and the subsequent unfolding of the protein (ACS, 1998). This disruption effectively halts viral replication and produces non-infectious viral particles, offering a strategy that may overcome resistance to traditional protease and reverse transcriptase inhibitors (PNAS, 1998).

Other names

NCp7Nucleocapsid protein p7NCGag-p7Zinc knuckle domains of HIV-1 NCCCHC-type zinc finger domains

Zinc ejection through covalent modification of the CCHC zinc-coordinating cysteine residues, leading to protein denaturation and loss of nucleic acid chaperone and packaging functions (Wikipedia, 2024; ACS, 1998).