The SARS-coronavirus nsp7+nsp8 complex is a unique multimeric RNA polymerase capable of both de novo initiation and primer extension

te Velthuis, Aartjan J.W.; van den Worm, Sjoerd H. E.; Snijder, Eric J.

Uniquely among RNA viruses, however, current evidence suggests that at least two RdRp activities are encoded by the genomes of members of the coronavirus (CoV) family, the +RNA virus group that infects a wide range of vertebrates and is renowned for its exceptionally large polycistronic genome of $30 kilobases (6) . Both CoV RdRps belong to the set of 16 non-structural proteins (nsps) that are produced through proteolytic processing of the pp1a and pp1ab replicase precursor polyproteins, which both derive from translation of the genomic RNA (7, 8) . For the Severe Acute Respiratory Syndrome-associated coronavirus (SARS-CoV), which emerged in 2003 and caused worldwide concern due to the $10% mortality rate associated with infection of humans (6, 9) , the two replicase subunits with RdRp activity have been studied in some detail. The first is the 106-kDa nsp12, which contains the canonical viral RdRp motifs in its C-terminal part and employs a primerdependent initiation mechanism (10, 11) . The second polymerase, the 22-kDa nsp8, is unique for CoVs and was reported to be only capable of de novo RNA synthesis with a low fidelity on ssRNA templates (12) . Together, these observations inspired a hypothesis in which nsp8 would serve as an RNA primase, i.e. would synthesise short oligonucleotide primers for subsequent extension by the nsp12 'main RdRp' (12) .