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000904555 1001_ $$00000-0001-8771-1865$$aKuzikov, Maria$$b0$$eCorresponding author
000904555 245__ $$aIdentification of Inhibitors of SARS-CoV-2 3CL-Pro Enzymatic Activity Using a Small Molecule in Vitro Repurposing Screen
000904555 260__ $$aWashington, DC$$bACS Publications$$c2021
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000904555 520__ $$aCompound repurposing is an important strategy for the identification of effective treatment options against SARS-CoV-2 infection and COVID-19 disease. In this regard, SARS-CoV-2 main protease (3CL-Pro), also termed M-Pro, is an attractive drug target as it plays a central role in viral replication by processing the viral polyproteins pp1a and pp1ab at multiple distinct cleavage sites. We here report the results of a repurposing program involving 8.7 K compounds containing marketed drugs, clinical and preclinical candidates, and small molecules regarded as safe in humans. We confirmed previously reported inhibitors of 3CL-Pro and have identified 62 additional compounds with IC50 values below 1 μM and profiled their selectivity toward chymotrypsin and 3CL-Pro from the Middle East respiratory syndrome virus. A subset of eight inhibitors showed anticytopathic effect in a Vero-E6 cell line, and the compounds thioguanosine and MG-132 were analyzed for their predicted binding characteristics to SARS-CoV-2 3CL-Pro. The X-ray crystal structure of the complex of myricetin and SARS-Cov-2 3CL-Pro was solved at a resolution of 1.77 Å, showing that myricetin is covalently bound to the catalytic Cys145 and therefore inhibiting its enzymatic activity.
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000904555 7001_ $$0P:(DE-HGF)0$$aCostanzi, Elisa$$b1
000904555 7001_ $$0P:(DE-HGF)0$$aReinshagen, Jeanette$$b2
000904555 7001_ $$0P:(DE-HGF)0$$aEsposito, Francesca$$b3
000904555 7001_ $$0P:(DE-HGF)0$$aVangeel, Laura$$b4
000904555 7001_ $$0P:(DE-HGF)0$$aWolf, Markus$$b5
000904555 7001_ $$0P:(DE-HGF)0$$aEllinger, Bernhard$$b6
000904555 7001_ $$0P:(DE-HGF)0$$aClaussen, Carsten$$b7
000904555 7001_ $$0P:(DE-HGF)0$$aGeisslinger, Gerd$$b8
000904555 7001_ $$0P:(DE-HGF)0$$aCorona, Angela$$b9
000904555 7001_ $$0P:(DE-HGF)0$$aIaconis, Daniela$$b10
000904555 7001_ $$0P:(DE-HGF)0$$aTalarico, Carmine$$b11
000904555 7001_ $$0P:(DE-HGF)0$$aManelfi, Candida$$b12
000904555 7001_ $$0P:(DE-HGF)0$$aCannalire, Rolando$$b13
000904555 7001_ $$0P:(DE-Juel1)145921$$aRossetti, Giulia$$b14
000904555 7001_ $$0P:(DE-Juel1)172836$$aGossen, Jonas$$b15$$ufzj
000904555 7001_ $$0P:(DE-Juel1)181061$$aAlbani, Simone$$b16$$ufzj
000904555 7001_ $$0P:(DE-HGF)0$$aMusiani, Francesco$$b17
000904555 7001_ $$0P:(DE-HGF)0$$aHerzog, Katja$$b18
000904555 7001_ $$0P:(DE-HGF)0$$aYe, Yang$$b19
000904555 7001_ $$0P:(DE-HGF)0$$aGiabbai, Barbara$$b20
000904555 7001_ $$0P:(DE-HGF)0$$aDemitri, Nicola$$b21
000904555 7001_ $$0P:(DE-HGF)0$$aJochmans, Dirk$$b22
000904555 7001_ $$0P:(DE-HGF)0$$aJonghe, Steven De$$b23
000904555 7001_ $$0P:(DE-HGF)0$$aRymenants, Jasper$$b24
000904555 7001_ $$0P:(DE-HGF)0$$aSumma, Vincenzo$$b25
000904555 7001_ $$0P:(DE-HGF)0$$aTramontano, Enzo$$b26
000904555 7001_ $$0P:(DE-HGF)0$$aBeccari, Andrea R.$$b27
000904555 7001_ $$0P:(DE-HGF)0$$aLeyssen, Pieter$$b28
000904555 7001_ $$0P:(DE-HGF)0$$aStorici, Paola$$b29
000904555 7001_ $$0P:(DE-HGF)0$$aNeyts, Johan$$b30
000904555 7001_ $$0P:(DE-HGF)0$$aGribbon, Philip$$b31
000904555 7001_ $$0P:(DE-HGF)0$$aZaliani, Andrea$$b32
000904555 773__ $$0PERI:(DE-600)2934670-8$$a10.1021/acsptsci.0c00216$$gVol. 4, no. 3, p. 1096 - 1110$$n3$$p1096 - 1110$$tACS pharmacology & translational science$$v4$$x2575-9108$$y2021
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