冠状病毒Coronavirusl论文-2006 [Annual Reports in Medicinal Chemistry] Annual Reports in Medicinal Chemistry Volume 41 Volume 41 __ Progress in An.pdf

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1、ProgressinAnti-SARSCoronavirusChemistry,BiologyandChemotherapy1123ArunK.Ghosh,KaiXi,MichaelE.Johnson,SusanC.Bakerand2AndrewD.Mesecar1DepartmentsofChemistryandMedicinalChemistry,PurdueUniversity,WestLafayette,IN,USA2CenterforPharmaceuticalBiotechnologyandDepartmentofMedicinalCh

2、emistryandPharmacognosy,UniversityofIllinoisatChicago,IL,USA3DepartmentofMicrobiologyandImmunology,LoyolaUniversityMedicalCenter,IL,USAContents1.Introduction1832.SARScoronavirusproteases1843.SARS-CoV3CLproinhibitors1853.1.CovalentinhibitorsofSARS-CoV3CLpro1863.2.Non-covalentSA

3、RS-CoV3CLproinhibitors1873.3.SARS-CoV3CLproinhibitorsfromscreening1904.PLproinhibitors1915.Viralentryinhibitors1926.Miscellaneousinhibitors1937.Futureoutlook194Acknowledgments194References1941.INTRODUCTIONSevereacuterespiratorysyndrome(SARS)wasfirstreportedinGuangdongProvince,C

4、hina,inNovember2002.Sincethen,ithasspreadtootherAsiancountries,NorthAmericaandEurope.Thisoutbreakreportedlyaffectedmorethan8000individualsbyJuly2003,andresultedin774deaths.SARSischaracterizedbyhighfever,malaise,rigor,headacheandnon-productivecoughordyspneaandmayprogresstogener

5、-alizedinterstitialinfiltratesinthelung,requiringintubationandmechanicalventi-lation[1].Inanunprecedentedresponse,theWorldHealthOrganization(WHO)calleduponleadinglaboratoriesintheworldandsetupmulti-centerresearchtoinvestigatetheetiologyofSARSanddevelopeffectivediagnostictests.W

6、iththeaidofmoderninformationtechnologies,WHOsetupasecuredwebsitetoshareemergingscientificinformationamongseverallaboratories.Thecriticalresultsincludingelec-tronmicrographsofviruses,sequencesofgeneticmaterial,identificationandchar-acterizationofthevirus,virusisolates,samplesfrom

7、patients,andpostmortemtissuesweresharedinrealtime.ThegoalwastopindownthecausativeagentforSARSandtodevelopdiagnostictools.Withinmonths,anovelcoronaviruswasisolatedfromANNUALREPORTSINMEDICINALCHEMISTRY,VOLUME41r2006ElsevierInc.ISSN:0065-7743DOI10.1016/S0065-7743(06)41011-3Allrig

8、htsreserved184A.K.Ghoshetal.patientswithSARS.Thenwithindays,a