Viral RNA replication and translation machinery (RTC)

The viral RNA replication and translation machinery is a multi-component assembly of viral proteins and co-opted host factors essential for the life cycle of RNA viruses (Subissi et al., 2014, Nature Reviews Microbiology). At its core is the RNA-dependent RNA polymerase (RdRp), which works in tandem with helicases, exonucleases, and proteases to replicate the viral genome and transcribe messenger RNA (Hillen et al., 2020, Nature). This machinery also facilitates the hijacking of host ribosomes and translation initiation factors to ensure the preferential synthesis of viral proteins over host proteins (Walsh & Mohr, 2011, Nature Reviews Microbiology). Because many components of this machinery, such as the RdRp, have no functional equivalents in human cells, they serve as high-priority targets for broad-spectrum and virus-specific antivirals (Pruijssers & Denison, 2019, Current Opinion in Virology). Drugs like remdesivir and sofosbuvir act as nucleoside analogs that incorporate into the growing RNA strand, causing premature termination of the replication process (Gordon et al., 2020, Nature). However, the high error rate of viral replication often leads to the emergence of resistant mutations, posing a significant challenge for long-term therapeutic efficacy (Agostini et al., 2018, mBio).

Other names

Replication-transcription complexViral replicase complexViral replication machineryRNA-dependent RNA polymerase complex

Inhibition of RNA-dependent RNA polymerase (RdRp) leading to chain termination or lethal mutagenesis; inhibition of viral proteases to prevent polyprotein cleavage; interference with viral RNA capping and translation initiation.