Zinc Finger Inhibitor - Zinc Finger Inhibitor Target: Nucleocapsid Protein

Zinc Finger Inhibitor Target: Nucleocapsid Protein

The HIV-1 nucleocapsid protein 7 (NCp7) is the protein targeted by zinc ejectors. NCp7 is initially formed as part of the gag polypeptide and follows a gag-knuckle zinc finger conformation. In its lifetime, NCp7 facilitates the unwinding of tRNA, acts as a primer for reverse transcription, chaperones nucleic acids within the capsid of HIV-1, helps integrate the viral RNA into budding virions, and is intimately involved in the replication of HIV-1 in both the early phase and late phase. These processes play critical roles in the replication of HIV-1 thus making NCp7 a prime target for drugs seeking to contravene the replication process.

NCp7 is a 55-amino acid protein that is highly basic and consists of two gag-knuckle motifs. These motifs contain two peptide units of Cys-X2-Cys-X4-His-X4-Cys (CCHC), where the X represents a substituted amino acid, that make up the zinc (II) ion binding sites. The binding of zinc (II) in the CCHC binding site is necessary for the domain to be functional and for the stabilization of the conformation of the structure, allowing the NCp7 to carry out the processes required for HIV replication. Since the CCHC binding site is mutation resistant and involved in the replication of HIV-1, it makes a prime candidate for the prevention of HIV through zinc ejectors. By inhibiting the function of NCp7, the viral replication is affected and a non-functional virus that is unable to infect its host is produced.