Structure-Based Discovery of a Novel Angiotensin-Converting Enzyme 2 Inhibitor

doi:10.1161/01.HYP.0000146120.29648.36

Paper

Structure-Based Discovery of a Novel Angiotensin-Converting Enzyme 2 Inhibitor

Published Dec 1, 2004 · M. Huentelman, J. Zubcevic, J. H. Prada

Hypertension

Q1 SJR score

171

Citations

8

Influential Citations

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Abstract

Angiotensin-converting enzyme 2 (ACE2) is considered an important therapeutic target for controlling cardiovascular diseases and severe acute respiratory syndrome (SARS) outbreaks. Recently solved high-resolution crystal structures of the apo-bound and inhibitor-bound forms of ACE2 have provided the basis for a novel molecular docking approach in an attempt to identify ACE2 inhibitors and compounds that block SARS coronavirus spike protein-mediated cell fusion. In this study, ≈140 000 small molecules were screened by in silico molecular docking. In this structure–activity relation study, the molecules with the highest predicted binding scores were identified and assayed for ACE2 enzymatic inhibitory activity and for their ability to inhibit SARS coronavirus spike protein-mediated cell fusion. This approach identified N-(2-aminoethyl)-1 aziridine-ethanamine as a novel ACE2 inhibitor that also is effective in blocking the SARS coronavirus spike protein-mediated cell fusion. Thus, the molecular docking approach resulting in the inhibitory capacity of N-(2-aminoethyl)-1 aziridine-ethanamine provides an attractive small molecule lead compound on which the development of more effective therapeutic agents could be developed to modulate hypertension and for controlling SARS infections.

In Vitro Study

Highly Cited

Study Snapshot

N-(2-aminoethyl)-1 aziridine-ethanamine is a novel ACE2 inhibitor that also effectively blocks SARS coronavirus spike protein-mediated cell fusion, offering potential for developing effective therapeutic agents to control hypertension and SARS infections.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

Structure-Based Discovery of a Novel Angiotensin-Converting Enzyme 2 Inhibitor

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References

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ACE2 X-Ray Structures Reveal a Large Hinge-bending Motion Important for Inhibitor Binding and Catalysis

ACE2 crystal structures reveal a hinge-bending motion that plays a crucial role in inhibitor binding and catalysis, providing insights into enzyme activity and substrate specificity.

Citations

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