Significance Proofreading exonucleases contributing to replication fidelity in DNA viruses and cellular organisms are well known; however, proofreading in RNA viruses was unknown until recently. Coronavirus nonstructural protein 14 (nsp14) has been shown to function as a proofreading exoribonuclease. Additionally, nsp14 shows (guanine-N7) methyl transferase activity for viral mRNA capping. Both roles are important for viral replication and transcription. Here, we report the structures of severe acute respiratory syndrome-coronavirus nsp14 in complex with its activator nonstructural protein 10 (nsp10) and functional ligands. Structural observations coupled with mutagenesis and functional assays provide a better understanding of the function of nsp14. Furthermore, the structures of the nsp14–nsp10 complex demonstrate several unique niches that could be targeted for development of potent antiviral drugs.

Structural basis and functional analysis of the SARS coronavirus nsp14–nsp10 complex