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10.1021/acs.jmedchem.1c02214

http://scihub22266oqcxt.onion/10.1021/acs.jmedchem.1c02214
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35549342!9115881!35549342
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suck abstract from ncbi


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pmid35549342      J+Med+Chem 2022 ; 65 (11): 7682-7696
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  • Penicillin Derivatives Inhibit the SARS-CoV-2 Main Protease by Reaction with Its Nucleophilic Cysteine #MMPMID35549342
  • Malla TR; Brewitz L; Muntean DG; Aslam H; Owen CD; Salah E; Tumber A; Lukacik P; Strain-Damerell C; Mikolajek H; Walsh MA; Schofield CJ
  • J Med Chem 2022[Jun]; 65 (11): 7682-7696 PMID35549342show ga
  • The SARS-CoV-2 main protease (M(pro)) is a medicinal chemistry target for COVID-19 treatment. Given the clinical efficacy of beta-lactams as inhibitors of bacterial nucleophilic enzymes, they are of interest as inhibitors of viral nucleophilic serine and cysteine proteases. We describe the synthesis of penicillin derivatives which are potent M(pro) inhibitors and investigate their mechanism of inhibition using mass spectrometric and crystallographic analyses. The results suggest that beta-lactams have considerable potential as M(pro) inhibitors via a mechanism involving reaction with the nucleophilic cysteine to form a stable acyl-enzyme complex as shown by crystallographic analysis. The results highlight the potential for inhibition of viral proteases employing nucleophilic catalysis by beta-lactams and related acylating agents.
  • |*COVID-19 Drug Treatment[MESH]
  • |*Cysteine[MESH]
  • |Antiviral Agents/chemistry/pharmacology[MESH]
  • |Coronavirus 3C Proteases[MESH]
  • |Cysteine Endopeptidases/chemistry[MESH]
  • |Humans[MESH]
  • |Penicillins[MESH]
  • |Protease Inhibitors/chemistry/pharmacology[MESH]
  • |SARS-CoV-2[MESH]


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