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10.1042/BCJ20210201

http://scihub22266oqcxt.onion/10.1042/BCJ20210201
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34198322!8286831!34198322
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suck abstract from ncbi


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pmid34198322      Biochem+J 2021 ; 478 (13): 2405-2423
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  • Identifying SARS-CoV-2 antiviral compounds by screening for small molecule inhibitors of nsp13 helicase #MMPMID34198322
  • Zeng J; Weissmann F; Bertolin AP; Posse V; Canal B; Ulferts R; Wu M; Harvey R; Hussain S; Milligan JC; Roustan C; Borg A; McCoy L; Drury LS; Kjaer S; McCauley J; Howell M; Beale R; Diffley JFX
  • Biochem J 2021[Jul]; 478 (13): 2405-2423 PMID34198322show ga
  • The coronavirus disease 2019 (COVID-19) pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global public health challenge. While the efficacy of vaccines against emerging and future virus variants remains unclear, there is a need for therapeutics. Repurposing existing drugs represents a promising and potentially rapid opportunity to find novel antivirals against SARS-CoV-2. The virus encodes at least nine enzymatic activities that are potential drug targets. Here, we have expressed, purified and developed enzymatic assays for SARS-CoV-2 nsp13 helicase, a viral replication protein that is essential for the coronavirus life cycle. We screened a custom chemical library of over 5000 previously characterized pharmaceuticals for nsp13 inhibitors using a fluorescence resonance energy transfer-based high-throughput screening approach. From this, we have identified FPA-124 and several suramin-related compounds as novel inhibitors of nsp13 helicase activity in vitro. We describe the efficacy of these drugs using assays we developed to monitor SARS-CoV-2 growth in Vero E6 cells.
  • |*Drug Evaluation, Preclinical[MESH]
  • |Animals[MESH]
  • |Antiviral Agents/*chemistry/*pharmacology[MESH]
  • |Chlorocebus aethiops[MESH]
  • |Enzyme Assays[MESH]
  • |Fluorescence Resonance Energy Transfer[MESH]
  • |High-Throughput Screening Assays[MESH]
  • |RNA Helicases/*antagonists & inhibitors/metabolism[MESH]
  • |Reproducibility of Results[MESH]
  • |SARS-CoV-2/drug effects/*enzymology[MESH]
  • |Small Molecule Libraries/chemistry/*pharmacology[MESH]
  • |Suramin/pharmacology[MESH]
  • |Vero Cells[MESH]


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