Zoe Yeoh, her mentors Dr. Janet Smith and Dr. Melanie Ohi, and several collaborators provide new insights into ZAP-mediated attenuation of viruses in research recently published in PNAS. In cells, ZAP (zinc-finger antiviral protein) and KHNYN (KH-like and NYN domain containing protein) act together with partners to recognize and deplete viral RNA containing CpG dinucleotide clusters. Using purified recombinant proteins and biochemical assays, the researchers defined a minimal ZAP:KHNYN complex that degrades single-stranded RNA and proposed a model for how this core would interact with viral RNA that contains CpG clusters.