Viral mRNA capping enzyme complex (VCE)

The viral mRNA capping enzyme complex is a critical multi-enzymatic machinery responsible for the 5-modification of viral transcripts, a process essential for viral fitness and host immune subversion. This machinery typically executes a three-to-four step reaction involving RNA triphosphatase, guanylyltransferase, N7-methyltransferase, and often 2-O-methyltransferase activities to create a cap-0 or cap-1 structure (Decroly et al., 2012). These modifications protect viral RNA from degradation by 5-3 exoribonucleases and facilitate the recruitment of host translation initiation factors like eIF4E for protein synthesis (Viswanathan et al., 2020). Furthermore, the 2-O-methylation of the ribose sugar serves as a molecular self marker, allowing the virus to evade detection by host innate immune sensors such as RIG-I and the antiviral effects of IFIT proteins (Daffis et al., 2010). In some viruses, like influenza, the machinery employs a cap-snatching mechanism where host pre-mRNAs are cleaved to provide the necessary cap for viral messages (Hayden et al., 2018). Because these viral enzymes often possess distinct structural folds compared to their human counterparts, they are highly attractive targets for the development of specific antiviral therapies, such as the endonuclease inhibitor baloxavir marboxil (Dias et al., 2009).

Other names

Viral mRNA capping machineryViral RNA capping apparatusViral methyltransferase complexRNA guanylyltransferase and methyltransferaseViral 2-O-methyltransferaseViral N7-methyltransferase

Inhibition of cap-snatching endonuclease activity, competitive inhibition of S-adenosyl-L-methionine (SAM) binding to methyltransferase domains, and interference with guanylyltransferase-mediated covalent enzyme-GMP intermediate formation (Bougie & Bisaillon, 2004; Dias et al., 2009).