Viral RNA-dependent RNA polymerase and RNA capping enzyme (RdRp/CE)

Viral RNA-dependent RNA polymerase (RdRp) and RNA capping enzymes are essential components of the replication machinery for many RNA viruses, including Coronaviridae and Flaviviridae (UniProt P0C6X7). The RdRp is responsible for synthesizing new strands of viral RNA from an RNA template, a process that is not found in human cells, making it a highly specific target for antiviral drugs (UniProt P0C6X7). RNA capping enzymes, such as guanylyltransferases and methyltransferases, modify the 5' end of viral mRNA to ensure stability and facilitate translation by host ribosomes (PubMed 32770177). These capping modifications also help the virus evade detection by the host's innate immune system by mimicking host mRNA structures (PubMed 32770177). In many viruses, these enzymes work in concert within a large replication-transcription complex (RTC) to ensure efficient viral propagation (UniProt P0C6X7). Therapeutic strategies often involve nucleoside or nucleotide analogs, such as remdesivir or sofosbuvir, which act as alternative substrates for the RdRp (PubChem CID 121304016). These drugs lead to premature chain termination or the accumulation of deleterious mutations, effectively halting viral replication (PubChem CID 121304016). Because these enzymes are critical for the viral life cycle and lack direct human homologs, they remain primary targets for the development of broad-spectrum antivirals (NIH COVID-19 Treatment Guidelines).

Other names

RdRpRNA replicaseRNA-directed RNA polymeraseViral replication-transcription complexRTCnsp12nsp14nsp16

Inhibition of viral RNA synthesis through chain termination or lethal mutagenesis, and inhibition of mRNA capping or cap-snatching to prevent viral protein translation and immune evasion.