Probing the competitive inhibitor efficacy of frog-skin alpha helical AMPs identified against ACE2 binding to SARS-CoV-2 S1 spike protein as therapeutic scaffold to prevent COVID-19.
Angiotensin-Converting Enzyme 2
/ chemistry
Animals
Antimicrobial Cationic Peptides
/ chemistry
Anura
/ metabolism
COVID-19
/ prevention & control
Humans
Peptides
/ metabolism
Protein Binding
Protein Conformation, alpha-Helical
SARS-CoV-2
Spike Glycoprotein, Coronavirus
/ chemistry
COVID-19 Drug Treatment
Antimicrobial peptide
Brevinin
COVID-19
Conformational sampling
Conventional molecular dynamics
Dermaseptin
Magainin
Ocellatin
S1 spike protein
SARS-CoV-2
Semi-empirical calculation
Steered molecular dynamics
Journal
Journal of molecular modeling
ISSN: 0948-5023
Titre abrégé: J Mol Model
Pays: Germany
ID NLM: 9806569
Informations de publication
Date de publication:
24 Apr 2022
24 Apr 2022
Historique:
received:
18
11
2021
accepted:
06
04
2022
entrez:
24
4
2022
pubmed:
25
4
2022
medline:
27
4
2022
Statut:
epublish
Résumé
In COVID-19 infection, the SARS-CoV-2 spike protein S1 interacts to the ACE2 receptor of human host, instigating the viral infection. To examine the competitive inhibitor efficacy of broad spectrum alpha helical AMPs extracted from frog skin, a comparative study of intermolecular interactions between viral S1 and AMPs was performed relative to S1-ACE2p interactions. The ACE2 binding region with S1 was extracted as ACE2p from the complex for ease of computation. Surprisingly, the Spike-Dermaseptin-S9 complex had more intermolecular interactions than the other peptide complexes and importantly, the S1-ACE2p complex. We observed how atomic displacements in docked complexes impacted structural integrity of a receptor-binding domain in S1 through conformational sampling analysis. Notably, this geometry-based sampling approach confers the robust interactions that endure in S1-Dermaseptin-S9 complex, demonstrating its conformational transition. Additionally, QM calculations revealed that the global hardness to resist chemical perturbations was found more in Dermaseptin-S9 compared to ACE2p. Moreover, the conventional MD through PCA and the torsional angle analyses indicated that Dermaseptin-S9 altered the conformations of S1 considerably. Our analysis further revealed the high structural stability of S1-Dermaseptin-S9 complex and particularly, the trajectory analysis of the secondary structural elements established the alpha helical conformations to be retained in S1-Dermaseptin-S9 complex, as substantiated by SMD results. In conclusion, the functional dynamics proved to be significant for viral Spike S1 and Dermaseptin-S9 peptide when compared to ACE2p complex. Hence, Dermaseptin-S9 peptide inhibitor could be a strong candidate for therapeutic scaffold to prevent infection of SARS-CoV-2.
Identifiants
pubmed: 35461388
doi: 10.1007/s00894-022-05117-8
pii: 10.1007/s00894-022-05117-8
pmc: PMC9034900
doi:
Substances chimiques
Antimicrobial Cationic Peptides
0
Peptides
0
Spike Glycoprotein, Coronavirus
0
spike protein, SARS-CoV-2
0
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
128Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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