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10.3390/v13050873

http://scihub22266oqcxt.onion/10.3390/v13050873
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34068686!8170883!34068686
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suck abstract from ncbi


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pmid34068686      Viruses 2021 ; 13 (5): ä
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  • The Repurposed Drugs Suramin and Quinacrine Cooperatively Inhibit SARS-CoV-2 3CL(pro) In Vitro #MMPMID34068686
  • Eberle RJ; Olivier DS; Amaral MS; Gering I; Willbold D; Arni RK; Coronado MA
  • Viruses 2021[May]; 13 (5): ä PMID34068686show ga
  • Since the first report of a new pneumonia disease in December 2019 (Wuhan, China) the WHO reported more than 148 million confirmed cases and 3.1 million losses globally up to now. The causative agent of COVID-19 (SARS-CoV-2) has spread worldwide, resulting in a pandemic of unprecedented magnitude. To date, several clinically safe and efficient vaccines (e.g., Pfizer-BioNTech, Moderna, Johnson & Johnson, and AstraZeneca COVID-19 vaccines) as well as drugs for emergency use have been approved. However, increasing numbers of SARS-Cov-2 variants make it imminent to identify an alternative way to treat SARS-CoV-2 infections. A well-known strategy to identify molecules with inhibitory potential against SARS-CoV-2 proteins is repurposing clinically developed drugs, e.g., antiparasitic drugs. The results described in this study demonstrated the inhibitory potential of quinacrine and suramin against SARS-CoV-2 main protease (3CL(pro)). Quinacrine and suramin molecules presented a competitive and noncompetitive inhibition mode, respectively, with IC(50) values in the low micromolar range. Surface plasmon resonance (SPR) experiments demonstrated that quinacrine and suramin alone possessed a moderate or weak affinity with SARS-CoV-2 3CL(pro) but suramin binding increased quinacrine interaction by around a factor of eight. Using docking and molecular dynamics simulations, we identified a possible binding mode and the amino acids involved in these interactions. Our results suggested that suramin, in combination with quinacrine, showed promising synergistic efficacy to inhibit SARS-CoV-2 3CL(pro). We suppose that the identification of effective, synergistic drug combinations could lead to the design of better treatments for the COVID-19 disease and repurposable drug candidates offer fast therapeutic breakthroughs, mainly in a pandemic moment.
  • |Antiviral Agents/pharmacology[MESH]
  • |COVID-19 Drug Treatment[MESH]
  • |COVID-19 Vaccines/pharmacology[MESH]
  • |Coronavirus 3C Proteases/antagonists & inhibitors/*drug effects/metabolism[MESH]
  • |Cysteine Endopeptidases/metabolism[MESH]
  • |Drug Repositioning[MESH]
  • |Humans[MESH]
  • |Molecular Docking Simulation[MESH]
  • |Molecular Dynamics Simulation[MESH]
  • |Pandemics[MESH]
  • |Protease Inhibitors/pharmacology[MESH]
  • |Quinacrine/metabolism/*pharmacology[MESH]
  • |SARS-CoV-2/drug effects/metabolism/pathogenicity[MESH]
  • |Suramin/metabolism/*pharmacology[MESH]


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