Structure of SARS-CoV-2 Main Protease bound to Ipidacrine.

X-ray screening identifies active site and allosteric inhibitors of SARS-CoV-2 main protease.

Inhibition of SARS-CoV-2 main protease by allosteric drug-binding

3CL-PRO,3CLp,Main protease,Mpro,Non-structural protein 5,nsp5,SARS coronavirus main proteinase

SGFRKMAFPSGKVEGCMVQVTCGTTTLNGLWLDDVVYCPRHVICTSEDMLNPNYEDLLIRKSNHNFLVQAGNVQLRVIGH
SMQNCVLKLKVDTANPKTPKYKFVRIQPGQTFSVLACYNGSPSGVYQCAMRPNFTIKGSFLNGSCGSVGFNIDYDCVSFC
YMHHMELPTGVHAGTDLEGNFYGPFVDRQTAQAAGTDTTITVNVLAWLYAAVINGDRWFLNRFTTTLNDFNLVAMKYNYE
PLTQDHVDILGPLSAQTGIAVLDMCASLKELLQNGMNGRTILGSALLEDEFTPFDVVRQCSGVTFQ

Severe acute respiratory syndrome coronavirus 2

Co-crystallization with the compounds was achieved by equilibrating a 6.25 mg/ml protein solution in 20 mM HEPES buffer (pH 7.8) containing 1 mM DTT, 1 mMEDTA, and 150 mM NaCl against a reservoir solution of 100 mM MIB, pH 7.5, containing 25% w/w PEG 1500 and 5% v/v DMSO. Prior to crystallization compound solutions in DMSO were dried onto the wells of SwissCI 96-well plates. To obtain well-diffracting crystals in a reproducible way seeding was applied for crystal growth. Crystals appeared within a few hours and reached their final size after 2 - 3 days. Crystals were manually harvested and flash-frozen in liquid nitrogen for subsequent X-ray diffraction data collection.

EU project 101003551 - EXSCALATE4CoV (E4C)

HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY

SARS-CoV-2, mPro, COVID-!9, PEPTIDE BINDING PROTEIN