The newly identified Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2)has resulted in a global health emergency because of its rapid spread and high mortality.The molecular mechanism of interaction between host and viral genomic RNA is yet unclear.We demonstrate herein that SARS-CoV-2 genomic RNA,as well as the negative-sense RNA,is dynamically N6-methyladenosine(m6A)-modified in human and monkey cells.Combined RIP-seq and miCLIP analyses identified a total of 8 m6A sites at single-base resolution in the genome.Especially,epidemic strains with mutations at these identified m6A sites have emerged worldwide,and formed a unique cluster in the US as indicated by phylogenetic analysis.Further functional experiments showed that m6A methylation negatively regulates SARS-CoV-2 infection.SARS-CoV-2 infection also triggered a global increase in host m6A methylome,exhibiting altered localization and motifs of m6A methylation in mRNAs.Altogether,our results identify m6A as a dynamic epitranscriptomic mark mediating the virus-host interaction.