The Initial COVID-19 Reliable Interactive DNA Methylation Markers and Biological Implications

Abstract Earlier research has established the existence of reliable interactive genomic biomarkers. However, reliable DNA methylation biomarkers, not to mention interactiveness, have yet to be identified at the epigenetic level. This study, from 865,859 methylation sites, discovered two miniature sets of Infinium MethylationEPIC sites, each having eight CpG sites (genes) to interact with each other and disease subtypes. They led to nearly perfect (96.87-100% accuracy) prediction of COVID-19 patients from patients with other diseases or healthy controls. These CpG sites can jointly explain some post-COVID-19-related conditions. These CpG sites and the optimum performed genomic biomarkers reported in the literature rise to be potential druggable targets. Among these CpG sites, cg16785077 (gene MX1), cg25932713 (gene PARP9), and cg22930808 (gene PARP9) at DNA methylation levels indicate that the initial SARS-CoV-2 may be better treated as transcribed viral DNA into RNA virus, i.e., not as an RNA virus that has been concerned by scientists. Such a discovery can significantly change the scientific thinking and knowledge of viruses.