Synthetic Peptides That Antagonize the Angiotensin-Converting Enzyme-2 (ACE-2) Interaction with SARS-CoV-2 Receptor Binding Spike Protein.
J Med Chem
; 65(4): 2836-2847, 2022 02 24.
Article
in En
| MEDLINE
| ID: mdl-34328726
ABSTRACT
The SARS-CoV-2 viral spike protein S receptor-binding domain (S-RBD) binds ACE2 on host cells to initiate molecular events, resulting in intracellular release of the viral genome. Therefore, antagonists of this interaction could allow a modality for therapeutic intervention. Peptides can inhibit the S-RBDACE2 interaction by interacting with the protein-protein interface. In this study, protein contact atlas data and molecular dynamics simulations were used to locate interaction hotspots on the secondary structure elements α1, α2, α3, ß3, and ß4 of ACE2. We designed a library of discontinuous peptides based upon a combination of the hotspot interactions, which were synthesized and screened in a bioluminescence-based assay. The peptides demonstrated high efficacy in antagonizing the SARS-CoV-2 S-RBDACE2 interaction and were validated by microscale thermophoresis which demonstrated strong binding affinity (â¼10 nM) of these peptides to S-RBD. We anticipate that such discontinuous peptides may hold the potential for an efficient therapeutic treatment for COVID-19.
Full text:
1
Database:
MEDLINE
Main subject:
Peptides
/
Spike Glycoprotein, Coronavirus
/
Angiotensin-Converting Enzyme 2
Limits:
Humans
Language:
En
Year:
2022
Type:
Article