Targeting cap1 RNA methyltransferases as an antiviral strategy

Abstract

Methylation is one of the critical modifications that regulates numerous biological processes. Guanine capping and methylation at the 7^th position (m⁷G) have been shown to mature mRNA for increased RNA stability and translational efficiency. The m⁷G capped cap0 RNA remains immature and requires additional methylation at the first nucleotide (N1-2'-O-Me), designated as cap1, to achieve full maturation. This cap1 RNA with N1-2'-O-Me prevents its recognition by innate immune sensors as non-self. Viruses have also evolved various strategies to produce self-like capped RNAs with the N1-2'-O-Me that potentially evades the antiviral response and establishes an efficient replication. In this review, we focus on the importance of the presence of N1-2'-O-Me in viral RNAs and discuss the potential for drug development by targeting host and viral N1-2'-O-methyltransferases.

Keywords: 2′-O-methylation; MTr1; SAM; SARS-CoV-2; antiviral drug; cap snatching; influenza virus; methyltransferase; methyltransferase inhibitor; nsp16.