SevereAcuteRespiratorySyndrome(SARS)hasaffectedthousandsofindividuals,causingfever,andpneumoniawithamortalityrateestimatedat10-18%.Anovelcoronavirushasbeenidentifiedasthecauseagentanditsgenomehasbeensequenced.Humancoronavirusescausemildrespiratoryillnessandaccountsforaboutathirdofallcasesofthecommoncold.TheenvelopedSARSviruscontainsalarge+strandRNAgenome,approximately30,000nucleotides.ExaminationoftheSARScoronavirussequencesrevealsthatrepgenecoversover20,000nucleotidesandencodestwooverlappingpolyproteinscleavedbyviralproteasesintosmallerproteinproducts.Translationofthelongerpolyproteinencodedbytherepgenerequiresaribosomalframeshift.OtherviralgenesarepredictedtoencodethetransmembranespikeproteinSinvolvedinviralfusionwithhostcells,theenvelopeproteinE,themembraneproteinMandthenucleocapsidproteinNthatbindstotheRNAgenomeaswellasseveraladditionalopenreADIngframeswithunknownfunctions.Viralentryintothecellisfollowedbytranslationoftheviralrepgene,whichcodesforaviralproteasewithinthepolyprotein,Mproor3CLpro.TheSARS3CLprohasalsobeenverifiedinvitrotocleaveaftertheGlnresidueatLeu-Gln-(Ser,Ala,Gly),.PolypeptidesreleasedfromthepolyproteinsbythemainviralproteaseMproor3CLproincludetheviralpolymeraseandaprotease.Bothproductsareessentialforviralreplicationandtranscription.StructuralcrystalsofaporcinecoronavirusproteasewithatransitionstateinhibitorsuggestthatinhibitorsofthedistantlyrelatedrhinovirusproteaselikethedrugAG7088maybemodifiedtoproducedrugsthatblocktheSARSproteaseandviralreplication.BlockingentryoftheSARSvirusintocells,involvingrecognitionofcellularreceptorsbytheSspikeprotein,mayprovideanotherstrategyforthedevelopmentofdrugstotreatSARS.

Contributor:KosiGramatikoff,PhD,GlennCroston,PhD

REFERENCES:KanchanAetal.CoronavirusMainProteinase(3CLpro)Structure:BasisforDesignofAnti-SARSDrugs.Science,Publishedonline13May2003MarcoA.Marraetal.TheGenomeSequenceoftheSARS-AssociatedCoronavirusScience,Publishedonline1May2003PaulA.Rotaetal.CharacterizationofaNovelCoronavirusAssociatedwithSevereAcuteRespiratorySyndrome.Science,Publishedonline1May2003

================  蚂蚁淘在线  ================

免责声明：本文仅代表作者个人观点，与本网无关。其创作性以及文中陈述文字和内容未经本站证实，对本文以及其中全部或者部分内容、文字的真实性、完整性、及时性本站不做任何保证或承诺，请读者仅作参考，并请自行核实相关内容

版权声明：未经蚂蚁淘在线授权不得转载、摘编或利用其他方式使用上述作品。已经经本网授权使用作品的，应该授权范围内使用，并注明“来源：蚂蚁淘在线”。违反上述声明者，本网将追究其相关法律责任。