TY  - JOUR
AU  - Kuzikov, Maria
AU  - Costanzi, Elisa
AU  - Reinshagen, Jeanette
AU  - Esposito, Francesca
AU  - Vangeel, Laura
AU  - Wolf, Markus
AU  - Ellinger, Bernhard
AU  - Claussen, Carsten
AU  - Geisslinger, Gerd
AU  - Corona, Angela
AU  - Iaconis, Daniela
AU  - Talarico, Carmine
AU  - Manelfi, Candida
AU  - Cannalire, Rolando
AU  - Rossetti, Giulia
AU  - Gossen, Jonas
AU  - Albani, Simone
AU  - Musiani, Francesco
AU  - Herzog, Katja
AU  - Ye, Yang
AU  - Giabbai, Barbara
AU  - Demitri, Nicola
AU  - Jochmans, Dirk
AU  - Jonghe, Steven De
AU  - Rymenants, Jasper
AU  - Summa, Vincenzo
AU  - Tramontano, Enzo
AU  - Beccari, Andrea R.
AU  - Leyssen, Pieter
AU  - Storici, Paola
AU  - Neyts, Johan
AU  - Gribbon, Philip
AU  - Zaliani, Andrea
TI  - Identification of Inhibitors of SARS-CoV-2 3CL-Pro Enzymatic Activity Using a Small Molecule in Vitro Repurposing Screen
JO  - ACS pharmacology & translational science
VL  - 4
IS  - 3
SN  - 2575-9108
CY  - Washington, DC
PB  - ACS Publications
M1  - FZJ-2021-06125
SP  - 1096 - 1110
PY  - 2021
AB  - Compound 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.
LB  - PUB:(DE-HGF)16
UR  - <Go to ISI:>//WOS:000662229400007
DO  - DOI:10.1021/acsptsci.0c00216
UR  - https://juser.fz-juelich.de/record/904555
ER  -