简介：Wereportacompletegenomicsequenceofrareisolates(minorgenotype)oftheSARS-CoVfromSARSpatientsinGuangdong,China,wherethefirstfewcasesemerged.Themoststrikingdiscoveryfromtheisolateisanextra29-nucleotidesequencelocatedatthenucleotidepositionsbetween27,863and27,864(referredtothecompletesequenceofBJ01)withinanoverlappedregioncomposedofBGI-PUP5(BGI-postulateduncharacterizedprotein5)andBGI-PUP6upstreamoftheN(nucleocapsid)protein.Thediscoveryofthisminorgenotype,GD-Ins29,suggestsasignificantgeneticeventanddifferentiatesitfromthepreviouslyre-portedgenotype,thedominantformamongallsequencedSARS-CoVisolates.A17-ntsegmentofthisextrasequenceisidenticaltoasegmentofthesamesizeintwohumanmRNAsequencesthatmayinterferewithviralgenomereplicationandtranscriptioninthecytosoloftheinfectedcells.Itprovidesanewavenuefortheexplorationofthevirus-hostinteractioninviralevolution,hostpathogenesis,andvaccinedevelopment.

简介：TheR(replicase)proteinistheuniquelydefinednon-structuralprotein(NSP)responsibleforRNAreplication,mutationrateorfidelity,regulationoftranscrip-tionincoronavirusesandmanyotherssRNAviruses.Basedonourcompletegenomesequencesoffourisolates(BJ01-BJ04)ofSARS-CoVfromBeijing,China,weanalyzedthestructureandpredictedfunctionsoftheRproteinincomparisonwith13otherisolatesofSARS-CoVand6othercoronaviruses.TheentireORF(open-readingframe)encodesfortwomajorenzymeactivities,RNA-dependentRNApolymerase(RdRp)andproteinaseactivities.TheRpolyproteinunder-goesacomplexproteolyticprocesstoproduce15function-relatedpeptides.Ahydrophobicdomain(HOD)andahydrophilicdomain(HID)arenewlyidentifiedwithinNSP1.ThesubstitutionrateoftheRproteinisclosetotheaverageoftheSARS-CoVgenome.ThefunctionaldomainsinallNSPsoftheRproteingivedifferentphylogeneticresultsthatsuggesttheirdifferentmutationrateunderselectivepressure.ElevenhighlyconservedregionsinRdRpandtwelvecleavagesitesby3CLP(chymotrypsin-likeprotein)havebeenidentifiedaspotentialdrugtargets.Findingssuggestthatitispossibletoobtaininformationaboutthephy-logenyofSARS-CoV,aswellaspotentialtoolsfordrugdesign,genotypinganddiagnosticsofSARS.