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Coronavirus encodes the 2'-O-MTase (2'O Methyltransferase) that is composed of the catalytic subunit nsp16 and the stimulatory subunit nsp10 and plays an important role in virus genome replication and evasion from innate immunity during viral infection. Nonstructural protein 16 (NSP16) / viral 2'O-methyltransferase (2'O-MTase) is highly conserved. The conserved 2'O-MTase activity is important for CoV pathogenesis and NSP16 is a conserved universal target for rapid live attenuated vaccine design in an expanding Coronavirus outbreak setting, such as COVID-19. Targeting the 2'O-methylation pathway on SARS-CoV replication and pathogenesis can be the treatment options for vaccine and anti-viral drug development which can against SARS-CoV-2,SARS-CoV, MERS-CoV or other RNA and DNA viruses.