Exploring the Efficacy of Noncovalent SARS-CoV-2 Main Protease Inhibitors: A Computational Simulation Analysis Study.
Chem Biodivers
; 21(5): e202302089, 2024 May.
Article
em En
| MEDLINE
| ID: mdl-38526531
ABSTRACT
The SARS-CoV-2 main protease, as a key target for antiviral therapeutics, is instrumental in maintaining virus stability, facilitating translation, and enabling the virus to evade innate immunity. Our research focused on designing non-covalent inhibitors to counteract the action of this protease. Utilizing a 3D-QSAR model and contour map, we successfully engineered eight novel non-covalent inhibitors. Further evaluation and comparison of these novel compounds through methodologies including molecular docking, ADMET analysis, frontier molecular orbital studies, molecular dynamics simulations, and binding free energy revealed that the inhibitors N02 and N03 demonstrated superior research performance (N02 ΔGbind=-206.648â
kJ/mol, N03 ΔGbind=-185.602â
kJ/mol). These findings offer insightful guidance for the further refinement of molecular structures and the development of more efficacious inhibitors. Consequently, future investigations can draw upon these findings to unearth more potent inhibitors, thereby amplifying their impact in the treatment and prevention of associated diseases.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Antivirais
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Inibidores de Proteases
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Relação Quantitativa Estrutura-Atividade
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Simulação de Dinâmica Molecular
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Simulação de Acoplamento Molecular
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Proteases 3C de Coronavírus
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SARS-CoV-2
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article