Viral RNA-dependent RNA polymerase with mRNA capping enzyme activities (viral L protein)

The viral RNA-dependent RNA polymerase (RdRp) with mRNA capping enzyme activities is a large, multifunctional enzyme complex required for the replication and transcription of the viral genome and capping of viral mRNAs[3][7]. The enzyme catalyzes RNA synthesis (polymerase activity), the transfer of a guanine nucleotide to the 5′ end of nascent viral transcripts (guanylyltransferase activity), methylation of the N7 position of guanine, and subsequent 2′-O-methylation of the first ribose, thereby forming the cap structure recognized by the host translation machinery and shielding viral RNA from immune detection. These activities are targets of direct-acting antivirals against a broad range of RNA viruses, including orthomyxoviruses, flaviviruses, and coronaviruses[7][3]. Inhibiting any of these steps can be detrimental to viral propagation, making the enzyme complex a prime candidate for therapeutic intervention.

Other names

Viral RNA-dependent RNA polymerase (RdRp)Viral L protein (in mononegavirales)Viral capping enzyme complexRNA guanylyltransferase (GTase)RNA (guanine-N7)-methyltransferasemRNA (nucleoside-2′-O)-methyltransferaseViral cap methyltransferase

Inhibition of RdRp: prevents viral RNA synthesis/replication (nucleoside analog chain-terminators, non-nucleoside inhibitors) Inhibition of mRNA capping enzymes: prevents addition of 5′ cap to viral mRNA, leading to transcript instability and loss of translational competence, as well as increased immune recognition (guanylyltransferase and methyltransferase inhibitors)