Viral mRNA capping enzyme (vCE)

Viral mRNA capping enzymes are essential proteins or protein domains used by many viruses to modify the 5' end of their nascent transcripts, mimicking the host's mRNA cap structure. This modification involves a multi-step process typically including RNA triphosphatase, guanylyltransferase, and methyltransferase activities to create cap-0 (m7GpppN) and cap-1 (m7GpppNm) structures. These caps are critical for protecting viral RNA from degradation by cellular exonucleases and for recruiting the host's translation machinery to produce viral proteins. Furthermore, the cap-1 structure serves as a 'self' marker, allowing the virus to evade detection by host innate immune sensors like RIG-I and IFIT proteins, which otherwise trigger an antiviral interferon response. Because viral capping enzymes often possess unique structural folds and mechanisms distinct from their eukaryotic counterparts, they are highly attractive targets for the development of broad-spectrum and virus-specific antiviral drugs.

Other names

Viral RNA capping enzymeRNA triphosphataseRNA guanylyltransferaseRNA (guanine-N7)-methyltransferaseRNA (nucleoside-2'-O)-methyltransferaseN7-MTase2'-O-MTase

Inhibition of RNA triphosphatase activity, competitive inhibition of guanylyltransferase by GTP analogues, and competitive inhibition of methyltransferase activity by S-adenosyl-L-methionine (SAM) analogues to prevent the formation of mature cap-0 and cap-1 structures.