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1、VirusResearch,14(1989)51-64ElsevierVIRUS00516InhibitionofmurinecoronavirusRNAsynthesisbyhydroxyguanidinederivativesJamesG.KeckI,Pou-HsiungWang*,EricJ.Lien*andMichaelM.C.Lai’IDepartmentofMicrobiology,SchoolofMedicineand2SectionofBiomedicinalChemistry,SchoolofPharmacy,UniversityofSouthernCalifornia
2、,LosAngeles,CA90033,U.S.A.(Accepted30May1989)SnmmaryAseriesofhydroxyguanidinederivatives,whicharesubstitutedsalicylaldehydeSchiff-basesof1-amino-3-hydroxyguanidinetosylate,weretestedfortheinhibitionofRNAsynthesisofmousehepatitisvirus(MHV).Itwasshownthatthesecompoundscouldselectivelyinhibitvirus-s
3、pecificRNAsynthesis.EveryaspectofviralRNAsynthesis,includingsynthesisofnegative-strandedRNA,subgenomicmRNAtranscriptionandgenomicRNAreplication,wasinhibitedtoroughlythesameextent.ThesecompoundsarethefirstknowninhibitorsofcoronaviralRNAsynthesisandshouldproveusefulforunderstandingthemechanismofvir
4、alRNAsynthesis.Mousehepatitisvirus;CoronavirusCoronavirusesareenvelopedRNAvirusesassociatedwithrespiratoryandgastro-intestinalillnessesinhumansandmanyotherspeciesofanimals(Wegeetal.,1982).Theprototypecoronavirus,mousehepatitisvirus(MHV),causeshepatitisandneurologicaldiseasesinmice.Thesevirusesemp
5、loyacomplexmechanismforthesynthesisofviralRNA(Lai,1987).Uponinfectionofasusceptiblecell,theviralgenomicRNA,whichisapositive-sensedsingle-strandedRNAofmorethan6xlo6daltons(LaiandStoleman,1978),isreleasedintothecytoplasmandusedforthetranslationofavirus-specificRNA-dependentRNApolymerase(Braytonetal
6、.,1982,1984).Thisenzyme,inturn,transcribestheviralRNAintoanegative-Correspondenceto:J.G.Keck,DepartmentofMicrobiology,SchoolofMedicine,UniversityofSouthernCalifornia,LosAngeles,CA90033,U.S.A.0168-1702/89/$03.5001989ElsevierSciencePublishersB.V.(BiomedicalDivision)58strandedRNAtemplate(Laietal.,19
7、82).AmodifiedornewRNApolymerase(Braytonetal.,1984)subsequentlysynthesizesvirus-specificmRNAsviaauniquemechanismofleader-primedtranscription,i.e.aleaderRNAissynthesizedinitially,dissociatedfromthetemplateRNAandthenrejoi
