Abstract
SARS-CoV-2 Spike protein RBD interacts with the hACE2 receptor to initiate cell entry and infection. We set out to develop lactam-based i,i + 4 stapled hACE2 peptides targeting SARS-CoV-2. In vitro screening demonstrates the inhibition of the Spike protein RBD-hACE2 complex formation by the hACE221-55A36K-F40E stapled peptide (IC50: 3.6 μM, Kd: 2.1 μM), suggesting that hACE2 peptidomimetics could form the basis for the development of anti-COVID-19 therapeutics.
MeSH terms
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Amino Acid Sequence
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Angiotensin-Converting Enzyme 2 / chemistry
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Angiotensin-Converting Enzyme 2 / metabolism*
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COVID-19 / metabolism*
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COVID-19 / virology
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Humans
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Peptides / chemistry
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Peptides / metabolism*
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Peptidomimetics
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SARS-CoV-2 / metabolism*
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Spike Glycoprotein, Coronavirus / antagonists & inhibitors
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Spike Glycoprotein, Coronavirus / chemistry
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Spike Glycoprotein, Coronavirus / metabolism*
Substances
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Peptides
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Peptidomimetics
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Spike Glycoprotein, Coronavirus
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spike protein, SARS-CoV-2
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ACE2 protein, human
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Angiotensin-Converting Enzyme 2