Pharmacophore Modeling Methods in Focused Library Selection – Applications in the Context of a New Classification Scheme

Luu, Tien T.T.; Malcolm, Noj; Nadassy, Katalin

doi:10.2174/138620711795767820

Cited by 11 publications

(2 citation statements)

References 51 publications

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“…A pharmacophore is a model which represents the key physicochemical interactions that mediate biological activity [156]. A pharmacophore model can be used for ligand-based virtual screening and to characterize molecular features of ligands and their structural requirements for biological interaction [157].…”

Section: Computational Models For Virtual Screening and Design Of Fprmentioning

confidence: 99%

Development of Small Molecule Non-peptide Formyl Peptide Receptor (FPR) Ligands and Molecular Modeling of Their Recognition

Schepetkin¹,

Khlebnikov²,

Giovannoni³

et al. 2014

CMC

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Formyl peptide receptors (FPRs) are G protein-coupled receptors (GPCRs) expressed on a variety of cell types. These receptors play an important role in the regulation of inflammatory reactions and sensing cellular damage. They have also been implicated in the pathogenesis of various diseases, including neurodegenerative diseases, cataract formation, and atherogenesis. Thus, FPR ligands, both agonists and antagonists, may represent novel therapeutics for modulating host defense and innate immunity. A variety of molecules have been identified as receptor subtype-selective and mixed FPR agonists with potential therapeutic value during last decade. This review describes our efforts along with recent advances in the identification, optimization, biological evaluation, and structure-activity relationship (SAR) analysis of small molecule non-peptide FPR agonists and antagonists, including chiral molecules. Questions regarding the interaction at the molecular level of benzimidazoles, pyrazolones, pyridazin-3(2H)-ones, N-phenylureas and other derivatives with FPR1 and FPR2 are discussed. Application of computational models for virtual screening and design of FPR ligands is also considered.

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Section: Computational Models For Virtual Screening and Design Of Fprmentioning

confidence: 99%

Development of Small Molecule Non-peptide Formyl Peptide Receptor (FPR) Ligands and Molecular Modeling of Their Recognition

Schepetkin¹,

Khlebnikov²,

Giovannoni³

et al. 2014

CMC

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“…Spike protein is a homotrimer, so we chose chain A for the analysis containing all the respective domains. The active site of the target protein was predicted by using binding site module using Discovery studio [21,22]. The functional active site was present in the receptor binding domain (Leu 335 to Gly 526), which also comprised the speci c active site region or loop region (NAG of RCSB: 6VSB, chain A) ( Figure 1).…”

Section: Preparation Of Receptor Protein and Active Site Predictionmentioning

confidence: 99%

A new proposed mechanism of some known drugs targeting the SARS-CoV-2 spike glycoprotein using molecular docking

Moussa

Sabry

2020

Preprint

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COVID-19 is caused by the novel enveloped beta-coronavirus with a genomic RNA closely related to severe acute respiratory syndrome-corona virus (SARS-CoV) and is named coronavirus 2 (SARS-CoV-2). The receptor binding domain (RBD) of the S-protein interacts with the human ACE-2 receptor that enables the initiation of viral entry. Hence, blocking the S-protein interactions by means of synthetic compounds mark the pivotal step for targeting SARS-CoV-2. Most of the six compounds were observed to fit nicely with specific noncovalent interactions, including H bonds, electrostatic, Van der Waals and hydrophobic bonds (pi and sigma bonds). Oseltamivir was found to be the most strongly interacting with the RBD, exhibiting high values of full fitness and low free energy of binding. it formed multiple noncovalent bonds in the region of the active site. Hydroxychloroquine also demonstrated high binding affinity in the solvent accessbility state and fit nicely into the active pocket of the S-protein. The results revealed that these compounds could be potent inhibitors of S-protein that could, to some extent, block its interaction with ACE-2. It is obvious from the 3D structure of SARS-CoV-2 spike protein was changed with the interaction of different drugs, which led to the unsuitability to bind ACE2 receptor. Hence, laboratory studies elucidating the action of these compounds on SARS-CoV-2 are warranted for clinical assessments. Chloroquine, hydroxychloroquine and oseltamivir interacted well with the receptor binding domain of S-protein via noncovalent interactions and recommended as excellent candidates for COVID-19.

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Lead Generation Based on Compound Collection Screening

Weigelt

Dorange²

2016

Methods and Principles in Medicinal Chemistry

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Pharmacophore Modeling Methods in Focused Library Selection – Applications in the Context of a New Classification Scheme

Cited by 11 publications

References 51 publications

Development of Small Molecule Non-peptide Formyl Peptide Receptor (FPR) Ligands and Molecular Modeling of Their Recognition

Development of Small Molecule Non-peptide Formyl Peptide Receptor (FPR) Ligands and Molecular Modeling of Their Recognition

A new proposed mechanism of some known drugs targeting the SARS-CoV-2 spike glycoprotein using molecular docking

Lead Generation Based on Compound Collection Screening

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