Figure 12.

Structure of the SARS-CoV-2 multiprotein replication–transcription complex (RTC). Surface representation (PDB 7KRN) (ref (143)) of the RTC highlighting the relative positions of the RNA-dependent RNA polymerase (RdRp, NSP12), processivity cofactors (NSP7 and NSP8), and the viral helicase (NSP13) as determined by single-particle cryo-EM. The NTP entry tunnel (inset) plays a critical role in the backtracking/proofreading function of the RTC, as erroneously incorporated ribonucleotides are frayed into the entry tunnel where they can then be removed by the 3′-5′ exonuclease, NSP14, to ensure high-fidelity replication of the viral genome. Created with BioRender.