Günther, SebastianSebastianGüntherReinke, PatrickPatrickReinkeFernández-Garciá, YaizaYaizaFernández-GarciáLieske, JuliaJuliaLieskeLane, ThomasThomasLaneGinn, Helen MaryHelen MaryGinnKoua, Faisal H. M.Faisal H. M.KouaEhrt, ChristianeChristianeEhrtEwert, WiebkeWiebkeEwertOberthür, DominikDominikOberthürYefanov, OleksandrOleksandrYefanovMeier, SusanneSusanneMeierLorenzen, KristinaKristinaLorenzenKrichel, BorisBorisKrichelKopicki, Janine-DeniseJanine-DeniseKopickiGelisio, LucaLucaGelisioBrehm, WolfgangWolfgangBrehmDunkel, IlonaIlonaDunkelSeychell, BrandonBrandonSeychellGieseler, HenryHenryGieselerNorton-Baker, BrennaBrennaNorton-BakerEscudero-Pérez, BeatrizBeatrizEscudero-PérezDomaracky, MartinMartinDomarackySaouane, SofianeSofianeSaouaneTolstikova, AleksandraAleksandraTolstikovaWhite, Thomas A.Thomas A.WhiteHänle, AnnaAnnaHänleGroessler, MichaelMichaelGroesslerFleckenstein, HolgerHolgerFleckensteinTrost, FabianFabianTrostGalchenkova, MarinaMarinaGalchenkovaGevorkov, YaroslavYaroslavGevorkovLi, ChufengChufengLiAwel, SalahSalahAwelPeck, ArianaArianaPeckBarthelmess, MiriamMiriamBarthelmessSchlünzen, FrankFrankSchlünzenXavier, Paulrajpillai LourduPaulrajpillai LourduXavierWerner, NadineNadineWernerAndaleeb, HinaHinaAndaleebUllah, NajeebNajeebUllahFalke, SvenSvenFalkeSrinivasan, VasundaraVasundaraSrinivasanFrancą, Bruno AlvesBruno AlvesFrancąSchwinzer, MartinMartinSchwinzerBrognaro, HévilaHévilaBrognaroRogers, CromarteCromarteRogersMelo, DiogoDiogoMeloZaitseva-Doyle, Joanna J.Joanna J.Zaitseva-DoyleKnoška, JurajJurajKnoškaPeña Murillo, Gisel E.Gisel E.Peña MurilloMashhour, Aida RahmaniAida RahmaniMashhourHennicke, VincentVincentHennickeFischer, PontusPontusFischerHakanpää, JohannaJohannaHakanpääMeyer, Jan H.Jan H.MeyerGribbon, PhilipPhilipGribbonEllinger, BernhardBernhardEllingerKuzikov, MariaMariaKuzikovWolf, MarkusMarkusWolfBeccari, Aandrea RosarioAandrea RosarioBeccariBourenkov, GlebGlebBourenkovStetten, David vonDavid vonStettenPompidor, GuillaumeGuillaumePompidorBento, IsabelIsabelBentoPanneerselvam, SaravananSaravananPanneerselvamKarpics, IvarsIvarsKarpicsSchneider, ThomasThomasSchneiderGarcia-Alai, Maria MartaMaria MartaGarcia-AlaiNiebling, StephanStephanNieblingGünther, ChristianChristianGüntherSchmidt, ChristinaChristinaSchmidtSchubert, RobinRobinSchubertHan, HuijongHuijongHanBoger, JulianeJulianeBogerMonteiro, Diana C.F.Diana C.F.MonteiroZhang, LinlinLinlinZhangSun, XinyuanyuanXinyuanyuanSunPletzer-Zelgert, JonathanJonathanPletzer-ZelgertWollenhaupt, JanJanWollenhauptFeiler, ChristianChristianFeilerWeiss, ManfredManfredWeissSchulz, Eike C.Eike C.SchulzMehrabi, PedramPedramMehrabiKarnǐcar, KatarinaKatarinaKarnǐcarUsenik, AleksandraAleksandraUsenikLoboda, JureJureLobodaTidow, HenningHenningTidowChari, AshwinAshwinChariHilgenfeld, RolfRolfHilgenfeldUetrecht, CharlotteCharlotteUetrechtCox, RussellRussellCoxZaliani, AndreaAndreaZalianiBeck, TobiasTobiasBeckRarey, MatthiasMatthiasRareyGünther, StephanStephanGüntherTurk, DusanDusanTurkHinrichs, WinfriedWinfriedHinrichsChapman, Henry N.Henry N.ChapmanPearson, ArwenArwenPearsonBetzel, ChristianChristianBetzelMeents, AlkeAlkeMeents2021-11-032021-11-032021-04-02Science / AAAS 372 (6542): 642-646 (2021)http://hdl.handle.net/11420/10624The coronavirus disease (COVID-19) caused by SARS-CoV-2 is creating tremendous human suffering. To date, no effective drug is available to directly treat the disease. In a search for a drug against COVID-19, we have performed a high-throughput X-ray crystallographic screen of two repurposing drug libraries against the SARS-CoV-2 main protease (Mpro), which is essential for viral replication. In contrast to commonly applied X-ray fragment screening experiments with molecules of low complexity, our screen tested alreadyapproved drugs and drugs in clinical trials. From the three-dimensional protein structures, we identified 37 compounds that bind to Mpro. In subsequent cell-based viral reduction assays, one peptidomimetic and six nonpeptidic compounds showed antiviral activity at nontoxic concentrations. We identified two allosteric binding sites representing attractive targets for drug development against SARS-CoV-2.en1095-9203Science / AAAS20216542642646American Association for the Advancement of Sciencehttps://creativecommons.org/licenses/by/4.0/NaturwissenschaftenX-ray screening identifies active site and allosteric inhibitors of SARS-CoV-2 main proteaseJournal Article10.15480/882.384810.1126/science.abf794510.15480/882.384833811162Journal Article