Zinc finger CCCH-type antiviral protein (ZAP)

Zinc finger CCCH-type antiviral protein (ZAP), also known as ZC3HAV1, is a potent host restriction factor that plays a central role in the innate immune response by inhibiting the replication of diverse viruses, including HIV-1, Ebola, and SARS-CoV-2 (UniProt KB Q7Z2W4). It functions by specifically recognizing and binding to CpG dinucleotides within viral RNA through its N-terminal zinc-finger domains, a mechanism that allows the cell to distinguish foreign genetic material from host RNA (Takata et al., Nature 2017). Upon binding, ZAP recruits a suite of cellular cofactors, such as the exosome complex and the 5'-3' exonuclease XRN1, to facilitate the degradation of viral mRNA and block the translation of viral proteins (NCBI Gene ID: 56829). ZAP exists in multiple isoforms, most notably ZAP-S and ZAP-L, which are differentially regulated by type I interferons to enhance the cellular antiviral state (Nchioua et al., mBio 2020). Beyond its antiviral properties, ZAP is involved in the regulation of host mRNA stability and has been implicated in cancer progression, where it may act as a tumor suppressor or promoter depending on the malignancy. While there are currently no FDA-approved drugs that directly target ZAP, it is a significant focus of research for developing broad-spectrum antivirals and improving the safety of oncolytic virus therapies.

Other names

ZC3HAV1PARP13Zinc finger CCCH domain-containing protein 2ZC3H2ZC3HDC2FLJ13288

Binding to CpG-rich viral RNA and recruitment of RNA degradation machinery (exosome, XRN1) to inhibit viral replication.