Unique and conserved features of genome and proteome of SARS-coronavirus, an early split-off from the coronavirus group 2 lineage

J Mol Biol. 2003 Aug 29;331(5):991-1004. doi: 10.1016/s0022-2836(03)00865-9.


The genome organization and expression strategy of the newly identified severe acute respiratory syndrome coronavirus (SARS-CoV) were predicted using recently published genome sequences. Fourteen putative open reading frames were identified, 12 of which were predicted to be expressed from a nested set of eight subgenomic mRNAs. The synthesis of these mRNAs in SARS-CoV-infected cells was confirmed experimentally. The 4382- and 7073 amino acid residue SARS-CoV replicase polyproteins are predicted to be cleaved into 16 subunits by two viral proteinases (bringing the total number of SARS-CoV proteins to 28). A phylogenetic analysis of the replicase gene, using a distantly related torovirus as an outgroup, demonstrated that, despite a number of unique features, SARS-CoV is most closely related to group 2 coronaviruses. Distant homologs of cellular RNA processing enzymes were identified in group 2 coronaviruses, with four of them being conserved in SARS-CoV. These newly recognized viral enzymes place the mechanism of coronavirus RNA synthesis in a completely new perspective. Furthermore, together with previously described viral enzymes, they will be important targets for the design of antiviral strategies aimed at controlling the further spread of SARS-CoV.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Chlorocebus aethiops
  • Conserved Sequence
  • Coronavirus / classification
  • Coronavirus / genetics*
  • Coronavirus / metabolism
  • Evolution, Molecular
  • Genome, Viral*
  • Humans
  • Molecular Sequence Data
  • Open Reading Frames
  • Phylogeny
  • Protein Structure, Tertiary
  • Protein Subunits
  • Proteome*
  • RNA Processing, Post-Transcriptional
  • RNA Replicase / chemistry
  • RNA Replicase / genetics
  • RNA Replicase / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Viral / genetics
  • RNA, Viral / metabolism
  • SARS Virus / classification
  • SARS Virus / genetics*
  • SARS Virus / metabolism
  • Sequence Homology, Amino Acid
  • Vero Cells
  • Viral Proteins / chemistry
  • Viral Proteins / genetics
  • Viral Proteins / metabolism


  • Protein Subunits
  • Proteome
  • RNA, Messenger
  • RNA, Viral
  • Viral Proteins
  • RNA Replicase

Associated data

  • GENBANK/AY274119
  • GENBANK/AY278741
  • RefSeq/NC_004718