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10.3390/molecules26113213

http://scihub22266oqcxt.onion/10.3390/molecules26113213
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34072087!8198929!34072087
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suck abstract from ncbi


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pmid34072087      Molecules 2021 ; 26 (11): ä
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  • Identification of SARS-CoV-2 Receptor Binding Inhibitors by In Vitro Screening of Drug Libraries #MMPMID34072087
  • David AB; Diamant E; Dor E; Barnea A; Natan N; Levin L; Chapman S; Mimran LC; Epstein E; Zichel R; Torgeman A
  • Molecules 2021[May]; 26 (11): ä PMID34072087show ga
  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19) global pandemic. The first step of viral infection is cell attachment, which is mediated by the binding of the SARS-CoV-2 receptor binding domain (RBD), part of the virus spike protein, to human angiotensin-converting enzyme 2 (ACE2). Therefore, drug repurposing to discover RBD-ACE2 binding inhibitors may provide a rapid and safe approach for COVID-19 therapy. Here, we describe the development of an in vitro RBD-ACE2 binding assay and its application to identify inhibitors of the interaction of the SARS-CoV-2 RBD to ACE2 by the high-throughput screening of two compound libraries (LOPAC((R))1280 and DiscoveryProbeTM). Three compounds, heparin sodium, aurintricarboxylic acid (ATA), and ellagic acid, were found to exert an effective binding inhibition, with IC50 values ranging from 0.6 to 5.5 microg/mL. A plaque reduction assay in Vero E6 cells infected with a SARS-CoV-2 surrogate virus confirmed the inhibition efficacy of heparin sodium and ATA. Molecular docking analysis located potential binding sites of these compounds in the RBD. In light of these findings, the screening system described herein can be applied to other drug libraries to discover potent SARS-CoV-2 inhibitors.
  • |*COVID-19 Drug Treatment[MESH]
  • |*Drug Discovery[MESH]
  • |Angiotensin-Converting Enzyme 2/genetics/*metabolism[MESH]
  • |Animals[MESH]
  • |Antiviral Agents/*pharmacology/therapeutic use[MESH]
  • |Aurintricarboxylic Acid/pharmacology/therapeutic use[MESH]
  • |COVID-19/virology[MESH]
  • |Chlorocebus aethiops[MESH]
  • |Ellagic Acid/pharmacology/therapeutic use[MESH]
  • |Heparin/pharmacology/therapeutic use[MESH]
  • |High-Throughput Screening Assays[MESH]
  • |Humans[MESH]
  • |Inhibitory Concentration 50[MESH]
  • |Molecular Docking Simulation[MESH]
  • |Protein Domains/genetics[MESH]
  • |Recombinant Proteins/genetics/metabolism[MESH]
  • |SARS-CoV-2/genetics/metabolism[MESH]
  • |Spike Glycoprotein, Coronavirus/*antagonists & inhibitors/genetics/metabolism[MESH]
  • |Vero Cells[MESH]


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