Inhibition of ACE2-S Protein Interaction by a Short Functional Peptide with a Boomerang Structure.
Molecules
; 29(13)2024 Jun 26.
Article
in En
| MEDLINE
| ID: mdl-38998974
ABSTRACT
Considering the high evolutionary rate and great harmfulness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is imperative to develop new pharmacological antagonists. Human angiotensin-converting enzyme-2 (ACE2) functions as a primary receptor for the spike protein (S protein) of SARS-CoV-2. Thus, a novel functional peptide, KYPAY (K5), with a boomerang structure, was developed to inhibit the interaction between ACE2 and the S protein by attaching to the ACE2 ligand-binding domain (LBD). The inhibition property of K5 was evaluated via molecular simulations, cell experiments, and adsorption kinetics analysis. The molecular simulations showed that K5 had a high affinity for ACE2 but a low affinity for the cell membrane. The umbrella sampling (US) simulations revealed a significant enhancement in the binding potential of this functional peptide to ACE2. The fluorescence microscopy and cytotoxicity experiments showed that K5 effectively prevented the interaction between ACE2 and the S protein without causing any noticeable harm to cells. Further flow cytometry research indicated that K5 successfully hindered the interaction between ACE2 and the S protein, resulting in 78% inhibition at a concentration of 100 µM. This work offers an innovative perspective on the development of functional peptides for the prevention and therapy of SARS-CoV-2.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Peptides
/
Protein Binding
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Spike Glycoprotein, Coronavirus
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Angiotensin-Converting Enzyme 2
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SARS-CoV-2
Limits:
Humans
Language:
En
Journal:
Molecules
Journal subject:
BIOLOGIA
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: