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Related Concept Videos

Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors01:30

Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors

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Angiotensin-converting enzyme (ACE), a vital component of the renin-angiotensin-aldosterone system, is abundant in lung endothelial cells. ACE converts the inactive decapeptide, angiotensin I, into the active octapeptide, angiotensin II. This potent vasoconstrictor narrows blood vessels, increasing resistance to blood flow and elevating blood pressure. Angiotensin II also stimulates aldosterone production, encouraging kidney cells to reabsorb more sodium and water from urine, thereby increasing...
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Transducer Mechanism: Enzyme-Linked Receptors01:27

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Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
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Enzyme-linked Receptors01:00

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Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
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In the renin-angiotensin-aldosterone system, a hormone called angiotensin II plays a crucial role. It binds to the AT1 receptors in vascular smooth muscles coupled with Gq proteins. The activation of these receptors activates an enzyme called phospholipase C, which releases two molecules: inositol trisphosphate and diacylglycerol. These molecules cause a chain reaction that leads to the phosphorylation of myosin light chains and promotes interaction between actin and myosin, leading to smooth...
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Heart Failure Drugs: Inhibitors of Renin-Angiotensin System01:26

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The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral...
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G Protein-coupled Receptors01:15

G Protein-coupled Receptors

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G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
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Engineering Antiviral Agents via Surface Plasmon Resonance
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Engineered soluble ACE2 receptor: Responding to change with change.

Guangyao Li1, Kewen Qian1, Shuyi Zhang1

  • 1Department of Biophysics, College of Basic Medical Sciences, Naval Medical University (Second Military Medical University), Shanghai, China.

Frontiers in Immunology
|February 6, 2023
PubMed
Summary

Recombinant soluble ACE2 shows promise for neutralizing coronaviruses, but clinical development is stalled. Further research is needed to overcome key challenges for its approval as a viable treatment.

Keywords:
ACE2 decoy receptorCOVID-19SARS coronavirus 2protein engineeringtherapeutic proteins

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Area of Science:

  • Virology
  • Drug Development
  • Biochemistry

Background:

  • Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) utilizes its S-spike protein to bind to the Angiotensin-Converting Enzyme 2 (ACE2) receptor for cellular invasion.
  • The interaction between viral receptor-binding sites and host cell receptors is a critical focus for developing effective coronavirus therapeutics.
  • Clinical progress of monoclonal antibody therapies, initially promising, is now showing signs of deceleration.

Purpose of the Study:

  • To evaluate the potential of recombinant soluble ACE2 as an alternative therapeutic strategy against SARS-CoV-2.
  • To identify key challenges hindering the clinical approval and widespread application of recombinant soluble ACE2 therapy.

Main Methods:

  • Review and analysis of engineering modifications applied to recombinant soluble ACE2.
  • Assessment of the safety and functional maturity of engineered recombinant soluble ACE2 variants.
  • Evaluation of the potential for broad coronavirus neutralization by recombinant soluble ACE2.

Main Results:

  • Recombinant soluble ACE2 has undergone significant engineering, enhancing its safety and functional properties.
  • This therapy demonstrates considerable potential for broadly neutralizing various coronaviruses.
  • Despite advancements, the clinical development of recombinant soluble ACE2 therapy has encountered significant delays.

Conclusions:

  • Recombinant soluble ACE2 represents a promising alternative to monoclonal antibodies for coronavirus treatment.
  • Addressing outstanding challenges is crucial for the expedited clinical approval of recombinant soluble ACE2.
  • Further research and development are imperative to translate the potential of recombinant soluble ACE2 into a clinically approved therapy.