Zinc finger antiviral protein (ZC3HAV1) (ZAP)

Zinc finger antiviral protein (ZAP), also known as ZC3HAV1, is a pivotal component of the host's innate immune system that targets and inhibits the replication of various RNA and DNA viruses (UniProt Q7Z2W4). It functions primarily by recognizing and binding to specific motifs in viral RNA, particularly CpG dinucleotides, which are often suppressed in host transcriptomes but prevalent in many viral genomes (Takata et al., 2017, Nature). Upon binding, ZAP recruits cellular degradation machinery, including the exosome complex and XRN1, to facilitate the rapid decay of viral transcripts (PubMed 28960625). Additionally, ZAP can block the translation of viral proteins by preventing the assembly of the translation initiation complex. The broader concept of zinc-dependent antiviral processes also includes the direct biochemical inhibition of viral enzymes, such as RNA-dependent RNA polymerase (RdRp) and proteases, by free zinc ions (Read et al., 2019, Adv Nutr). Therapeutic approaches in this area often involve the use of zinc ionophores, such as pyrithione or quercetin, to elevate intracellular zinc levels to disrupt the replication cycles of viruses like SARS-CoV and influenza (te Velthuis et al., 2010, PLoS Pathog). While ZAP is a specific protein target, the overall process relies on the availability of zinc as a structural cofactor or a direct inhibitory ion.

Other names

ZC3HAV1PARP13Zinc finger CCCH-type antiviral protein 1Zinc-dependent antiviral processes

Modulation of viral RNA stability through CpG-specific binding and recruitment of the RNA exosome complex, and direct inhibition of viral RNA-dependent RNA polymerase (RdRp) activity by zinc ions.