A complete sequence and comparative analysis of strain (BJ01) of the SARS- associated virus

The nucleotide sequence of the Severe Acute Respiratory Syndrome (SARS)-associated virus provides essential information for the identification of pathogen(s), exploration of etiology and evolution, interpretation of transmission and pathogenesis, development of diagnostics, prevention by future vaccines and treatment by newly de- veloped drugs for SARS. We report the complete genome sequence and comparative analysis of a strain, (BJ01) of the coronavirus, which has been recognized as a pathogen for SARS. The genome size is 29.725 kb with 6 putative protein coding sequences and 5 uncharacterize d ORFs (Opening Reading Frames). Its gene order is identical to that of other known coronaviruses. The whole genome is composed of a stable region encoding an RNA-dependent RNA polymerase (composed of 2 ORFs overlapped by a single nucleotide) and a variable region representing 4 viral structural genes (the S, E, M, N pr oteins). The sequence alignment with all known RNA viruses places this virus in the family of Coronaviridae. Thirty-one substitutions, with an estimated overall mutation rate of 0.1 %, have been revealed by comparative analysis on the 5 SARS-associated virus sequences in GenBank, Fifteen substitutions are predicted to lead to possible amino acid changes (non-synonymous mutations) in the putative proteins. Three amino acid changes, with predicted altera- tion of physical/chemical features, have been detected in the S protein, which is postulated to be involved in the immuno- reactions between the virus and its host. Two amino acid changes have been detected in the M protein. Phylogenetic analysis suggests the possibility of non -human origin of the SARS viruses, but no evidence for being man-made. Efforts still have to be made on the identification of i ts etiology or other possible pathogens related to SARS.