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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
