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Related Concept Videos

Combined Effects of Drugs: Synergism01:27

Combined Effects of Drugs: Synergism

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Synergism is a useful mechanism where combining two or more drugs is more effective than each constituent used alone. Such combinations are also called supra-additive interactions. The drugs collectively enhance the final therapeutic effect by acting on different targets. Another advantage is that the low dose of each constituent drug is sufficient to achieve the desired effect. This helps reduce the duration of therapy and lower the adverse effects of these drugs.
Such synergistic combinations...
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Related Experiment Video

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Live Imaging and Quantification of Viral Infection in K18 hACE2 Transgenic Mice Using Reporter-Expressing Recombinant SARS-CoV-2
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The Repurposed Drugs Suramin and Quinacrine Cooperatively Inhibit SARS-CoV-2 3CLpro In Vitro.

Raphael J Eberle1,2, Danilo S Olivier3, Marcos S Amaral4

  • 1Institute of Biological Information Processing (IBI-7: Structural Biochemistry), Forschungszentrum Jülich, 52428 Jülich, Germany.

Viruses
|June 2, 2021
PubMed
Summary

Repurposing the antiparasitic drugs quinacrine and suramin showed synergistic potential against SARS-CoV-2 main protease (3CLpro). This combination therapy offers a promising alternative for treating COVID-19 infections.

Keywords:
3CLproCOVID-19SARS-CoV-2main proteasequinacrinerepurposing approved drugssuramin

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High-throughput Confocal Imaging of Quantum Dot-Conjugated SARS-CoV-2 Spike Trimers to Track Binding and Endocytosis in HEK293T Cells

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Area of Science:

  • Virology and Drug Discovery
  • Infectious Diseases and Epidemiology

Background:

  • The COVID-19 pandemic, caused by SARS-CoV-2, has led to millions of deaths globally.
  • Emerging SARS-CoV-2 variants necessitate alternative therapeutic strategies beyond existing vaccines and emergency drugs.
  • Drug repurposing, particularly of antiparasitic agents, presents a viable approach to identify novel antiviral compounds.

Purpose of the Study:

  • To investigate the inhibitory potential of quinacrine and suramin against the SARS-CoV-2 main protease (3CLpro).
  • To explore the synergistic efficacy of combining quinacrine and suramin for potential COVID-19 treatment.

Main Methods:

  • In vitro enzyme inhibition assays to determine IC50 values for quinacrine and suramin.
  • Surface Plasmon Resonance (SPR) to analyze binding kinetics and affinity with SARS-CoV-2 3CLpro.
  • Molecular docking and dynamics simulations to elucidate binding modes and interactions.

Main Results:

  • Quinacrine and suramin demonstrated inhibitory potential against SARS-CoV-2 3CLpro with low micromolar IC50 values.
  • Quinacrine exhibited competitive inhibition, while suramin showed non-competitive inhibition.
  • Suramin significantly enhanced quinacrine's binding affinity to SARS-CoV-2 3CLpro by approximately eightfold.
  • Synergistic inhibitory effects were observed when quinacrine and suramin were used in combination.

Conclusions:

  • Quinacrine and suramin, when combined, exhibit promising synergistic efficacy against SARS-CoV-2 3CLpro.
  • This drug combination represents a potential therapeutic strategy for COVID-19 treatment.
  • Repurposed drug candidates offer rapid development pathways for novel antiviral therapies, especially during pandemics.