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Depolarizing Blockers: Pharmocokinetics01:19

Depolarizing Blockers: Pharmocokinetics

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Depolarizing blockers are administered through intravenous injection. Succinylcholine is the most common choice of depolarizing blockers in emergency clinical practices. Although they have a rapid onset, they readily diffuse away from the motor end plate into the extracellular fluid. They are metabolized by enzymes such as liver butyrylcholinesterase and plasma pseudocholinesterases. This produces a short duration of action, typically 5-10 minutes long, unlike nondepolarizing blockers, which...
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Depolarizing Blockers: Mechanism of Action01:28

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Depolarizing blockers act on skeletal muscle fibers' membranes and induce their depolarization. Most depolarizing blockers have two quaternary N+ atoms that bind the nicotinic acetylcholine receptors and cause neuromuscular blockade within minutes.
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The high insolubility of some precipitates can result in an unfavorable relative supersaturation. This can lead to colloidal particles with a large surface-to-mass ratio, where adsorption is promoted. For instance, in the precipitation of silver chloride, silver ions are adsorbed on the surface of the colloidal particles, forming a primary layer. This layer attracts ions of opposite charge (such as nitrate ions), forming a diffuse secondary layer of adsorbed ions. This electric double layer...
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Engineering Antiviral Agents via Surface Plasmon Resonance
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Polysulfates Block SARS-CoV-2 Uptake through Electrostatic Interactions*.

Chuanxiong Nie1,2, Paria Pouyan1, Daniel Lauster1

  • 1Institut für Chemie und Biochemie, Freie Universität Berlin, Arnimallee 22, 14195, Berlin, Germany.

Angewandte Chemie (International Ed. in English)
|April 16, 2021
PubMed
Summary
This summary is machine-generated.

Negatively charged polysulfates, like linear polyglycerol sulfate (LPGS), effectively inhibit SARS-CoV-2 by binding to its spike protein. LPGS shows superior antiviral activity and reduced anticoagulant effects compared to heparin, offering a blueprint for new viral inhibitors.

Keywords:
SARS-CoV-2electrostatic interactionsinhibitionpolysulfatesvirus binding

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Area of Science:

  • Virology
  • Biochemistry
  • Materials Science

Background:

  • SARS-CoV-2 spike protein mediates viral entry into host cells.
  • Polysulfates are negatively charged polymers with potential antiviral properties.
  • Understanding spike protein-polysulfate interactions is crucial for developing inhibitors.

Purpose of the Study:

  • To investigate the binding of negatively charged polysulfates to the SARS-CoV-2 spike protein.
  • To compare the inhibitory activity of different polysulfates against SARS-CoV-2.
  • To evaluate the potential of polysulfates as antiviral agents.

Main Methods:

  • Plaque reduction assays were used to determine the inhibitory concentration (IC50) of various polysulfates.
  • Molecular dynamics simulations were employed to study binding interactions between polysulfates and the spike protein.
  • Anticoagulant activity was assessed to compare safety profiles.

Main Results:

  • Negatively charged polysulfates bind to the SARS-CoV-2 spike protein via electrostatic interactions.
  • Linear polyglycerol sulfate (LPGS) demonstrated the highest inhibitory activity (IC50: 67 μg/mL), significantly outperforming heparin.
  • LPGS showed stronger binding to the spike protein, including variants with N501Y and E484K mutations, and exhibited lower anticoagulant activity.

Conclusions:

  • Polysulfates can effectively block SARS-CoV-2 entry through electrostatic interactions with the spike protein.
  • LPGS is a potent inhibitor of SARS-CoV-2 with a favorable safety profile.
  • LPGS serves as a promising lead compound for designing novel antiviral therapies against SARS-CoV-2 and its variants.