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1、RESEARCHHIGHLIGHTSNatureReviewsMicrobiology
2、AOP,publishedonline10September2013;doi:10.1038/nrmicro3125VIRALEVOLUTIONof5?FUmetabolites.Takentogether,theseresultsshowthatExoNproof?readingprotectsSARS?CoVfromtheFoolingthecoronavirusdeleteriouseffectsofmutagens,s
3、uchas5?FU.proofreadingmachineryTodate,noantiviraltreatmentexistsforcoronaviruses;neitherriba?virinnorinterferon?α,theonlytwoExoNThepolymeraseofRNAvirusescorruptessentialfunctions.Here,broadlyactingantiviralsavailableproofreadinglackstheproofreadingcapacitySmi
4、thet?al.revealthat,inthecaseofintheclinictoday,haveaconsistentfoundinthepolymeraseofDNAsevereacuterespiratorysyndromeantiviraleffectagainstSARS?CoV.protectsviruses,leadingtohigherrorcoronavirus(SARS?CoV),anHowever,becauseribavirinisaSARS?CoVratesandlowreplica
5、tivefidelity.exoribonucleasedomain(ExoN)inmutagenicnucleosideanalogue,itfromtheAlthoughthehighmutationrateofnon?structuralprotein?14providesmighthavesimilareffectsto5?FURNAvirusesenablesthemtoreadilyproofreadingactivitythatprotectsintheabsenceofExoN.Consisten
6、tdeleterious–adapttoenvironmentalchanges,thevirusfrommutagenesis.withthis,ExoNmurineCoVwaseffectsoftheyalsorisk‘lethalmutagenesis’Previousworkincoronaviruses,moresensitivetoribavirinthanmutagenswhenaccumulatingmutationsthelargestRNAviruses,hadshownExoN+murine
7、CoV,althoughthatExoNdeletionleadstoreducedfurtherexperimentsindicatedreplicativefidelityandattenuationofthatothermechanismsbesidesvirulence.Thus,Smithet?al.specu?mutagenesis(forexample,reducedlatedthatExoNisaproofreadingRNAsynthesis)contributedtothisenzyme.To
8、testthishypothesis,theyExoN?dependenteffect.Asthecellsinfectedcellswithwild?type(ExoN+)usedforSARS?CoVinfectionsfailedorExoN?deleted(ExoN–)SARS?CoVtotakeupribavirin,thesensitivityinthepresenceofthemutagenicofExoN–SARS?CoVtoribavirinpyrimidineanalogue5?fluorou
9、racilremainsunclear.(5?FU).Indeed,lossofExoNsensi?Nevertheless,coronavirusExoNtizedthevirusto5?FU,asshownisthefirstproofreadingproteinbya160?foldreductioninviralreportedinanRNAvirus,andre
