The zinc finger antiviral protein (ZAP) is known to restrict viral replication by binding to the CpG rich regions of viral RNA, and subsequently inducing viral RNA degradation. This enzyme has recently been shown to be capable of restricting SARS-CoV-2. These data have led to the hypothesis that the low abundance of CpG in the SARS-CoV-2 genome is due to an evolutionary pressure exerted by the host ZAP. To investigate this hypothesis, we performed a detailed analysis of many coronavirus sequences and ZAP RNA binding preference data. Our analyses showed neither evidence for an evolutionary pressure acting specifically on CpG dinucleotides, nor a link between the activity of ZAP and the low CpG abundance of the SARS-CoV-2 genome.
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This study is supported by funding from the UT Health San Antonio COVID-19 Rapid Response Pilot Program and San Antonio Partnership for Precision Medicine (SAPPT) to DE and ZX (Grant No. g341947). HAR is funded by the UNSW Scientia Program Fellowship, and AA is supported by an Australian Government Research Training Program (RTP) Scholarship.
Afrasiabi, Ali; Alinejad-Rokny, Hamid; Khosh, Azad; Rahnama, Mostafa; Lovell, Nigel; Xu, Zhenming; and Ebrahimi, Diako, "The Low Abundance of CpG in the SARS-CoV-2 Genome Is Not an Evolutionarily Signature of ZAP" (2022). Plant Pathology Faculty Publications. 104.