Identification of naphthyridine and quinoline derivatives as potential Nsp16-Nsp10 inhibitors: a pharmacoinformatics study
| Autor: | Amer M. Alanazi, Adel Mohamed Abdelhakem, Ataul Islam, Mohanad Yakdhan Saleh, Bilal J M Aldahham, Khattab Al-Khafaji |
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| Rok vydání: | 2020 |
| Předmět: |
Virtual screening
SARS-CoV-2 Stereochemistry Pharmacoinformatics In silico Quinoline Methyltransferases General Medicine Viral Nonstructural Proteins Ligands Ligand (biochemistry) Small molecule COVID-19 Drug Treatment Molecular Docking Simulation chemistry.chemical_compound Molecular dynamics chemistry Structural Biology Humans Molecule Naphthyridines Molecular Biology |
| Zdroj: | Journal of Biomolecular Structure and Dynamics. 40:3899-3906 |
| ISSN: | 1538-0254 0739-1102 |
| Popis: | This research is a recent effort to explore some new heterocyclic compounds as novel and potential nonstructural protein-16-nonstructural protein-10 (Nsp16-Nsp10) inhibitors for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inhibition. The SARS-CoV-2 is causative agent of coronavirus disease 2019 (COVID-19) pandemic. A set of 58 molecules belongs to the naphthyridine and quinoline derivatives have been recently synthesized and considered for structure-based virtual screening against Nsp16-Nsp10. Molecular docking was virtually performed to screen for anti-SARS-CoV-2 activity against Nsp16-Nsp10. Fourteen out of fifty-eight compounds were exhibited binding affinity higher than co-crystal bound ligand s-adenosylmethionine (SAM) toward Nsp16-Nsp10. Further, the in silico pharmacokinetics assessment was carried out and it was found that two molecules possess the acceptable pharmacokinetic profile, hence considered promising Nsp16-Nsp10 inhibitors. The binding interaction analysis was revealed some crucial binding interactions between the final selected two molecules and ligand-binding amino acid residues of Nsp16-Nsp10 protein. In order to explore the characteristics of the protein-ligand complex and how selected small molecules retained inside the receptor cavity in dynamic states, all-atoms conventional molecular dynamics (MD) simulation was performed. Several factors were obtained from the MD simulation trajectory evidently suggested the potentiality of the molecules and stability of the protein-ligand complex. Finally, the binding affinity of both molecules and SAM was explored through the MM-GBSA approach which explained that both molecules possess strong affection towards the Nsp16-Nsp10. Hence, from the pharmacoinformatics assessment, it can be concluded that both heterocyclic compounds might be crucial for SARS-CoV-2 inhibition, subjected to experimental validation.Communicated by Ramaswamy H. Sarma. |
| Databáze: | OpenAIRE |
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