Identification of natural product compounds as quorum sensing inhibitors in Pseudomonas fluorescens P07 through virtual screening

2018 ◽  
Vol 26 (14) ◽  
pp. 4088-4099 ◽  
Author(s):  
Ting Ding ◽  
Tingting Li ◽  
Jianrong Li
Keyword(s):  
Virtual Screening ◽  
Quorum Sensing ◽  
Pseudomonas Fluorescens ◽  
Natural Product ◽  
Quorum Sensing Inhibitors ◽  
Natural Product Compounds

Novel AI-2 quorum sensing inhibitors in Vibrio harveyi identified through structure-based virtual screening

2012 ◽  
Vol 22 (20) ◽  
pp. 6413-6417 ◽  
Author(s):  
Peng Zhu ◽  
Hanjing Peng ◽  
Nanting Ni ◽  
Binghe Wang ◽  
Minyong Li
Keyword(s):  
Virtual Screening ◽  
Quorum Sensing ◽  
Vibrio Harveyi ◽  
Quorum Sensing Inhibitors

scholarly journals Computer-Aided Identification of Recognized Drugs as Pseudomonas aeruginosa Quorum-Sensing Inhibitors

2009 ◽  
Vol 53 (6) ◽  
pp. 2432-2443 ◽  
Author(s):  
Liang Yang ◽  
Morten Theil Rybtke ◽  
Tim Holm Jakobsen ◽  
Morten Hentzer ◽  
Thomas Bjarnsholt ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Virtual Screening ◽  
Quorum Sensing ◽  
Bacterial Infections ◽  
Treatment Strategies ◽  
Significant Inhibition ◽  
Dependent Manner ◽  
Chronic Infections ◽  
Quorum Sensing Inhibitors ◽  
Regulated Gene Expression

ABSTRACT Attenuation of Pseudomonas aeruginosa virulence by the use of small-molecule quorum-sensing inhibitors (referred to as the antipathogenic drug principle) is likely to play a role in future treatment strategies for chronic infections. In this study, structure-based virtual screening was used in a search for putative quorum-sensing inhibitors from a database comprising approved drugs and natural compounds. The database was built from compounds which showed structural similarities to previously reported quorum-sensing inhibitors, the ligand of the P. aeruginosa quorum-sensing receptor LasR, and a quorum-sensing receptor agonist. Six top-ranking compounds, all recognized drugs, were identified and tested for quorum-sensing-inhibitory activity. Three compounds, salicylic acid, nifuroxazide, and chlorzoxazone, showed significant inhibition of quorum-sensing-regulated gene expression and related phenotypes in a dose-dependent manner. These results suggest that the identified compounds have the potential to be used as antipathogenic drugs. Furthermore, the results indicate that structure-based virtual screening is an efficient tool in the search for novel compounds to combat bacterial infections.

scholarly journals Energy-Optimized Pharmacophore Coupled Virtual Screening in the Discovery of Quorum Sensing Inhibitors of LasR Protein of Pseudomonas aeruginosa

2019 ◽  
Author(s):  
Zulkar Nain ◽  
Sifat Bin Sayed ◽  
Mohammad Minnatul Karim ◽  
Md. Ariful Islam ◽  
Utpal Kumar Adhikari
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Virtual Screening ◽  
Quorum Sensing ◽  
Bacterial Infections ◽  
Opportunistic Pathogen ◽  
Vital Role ◽  
Energy Calculation ◽  
Quorum Sensing Inhibitors ◽  
Binding Energy Calculation ◽  
Standard Precision

Pseudomonas aeruginosa is an emerging opportunistic pathogen responsible for cystic fibrosis and nosocomial infections. In addition, empirical treatments are become inefficient due to their multiple-antibiotic resistance and extensive colonizing ability. Quorum sensing (QS) plays a vital role in the regulation of virulence factors in P. aeruginosa. Attenuation of virulence by QS inhibition could be an alternative and effective approach to control infections. Therefore, we sought to discover new QS inhibitors (QSIs) against LasR receptor in P. aeruginosa using chemoinformatics. Initially, a structure-based high-throughput virtual screening was performed using the LasR active site that identified 61404 relevant molecules. E-pharmacophore (ADAHH) screening of these molecules rendered 72 QSI candidates. In standard-precision docking, only 7 compounds were found as potential QSIs due to their higher binding affinity to LasR receptor (-7.53 to -10.32 kcal/mol compared to -7.43 kcal/mol of native ligands). The ADMET properties of these compounds were suitable to be QSIs. Later, extra-precision docking and binding energy calculation suggested ZINC19765885 and ZINC72387263 as the most promising QSIs. The dynamic simulation of the docked complexes showed good binding stability and molecular interactions. The current study suggested that these two compounds could be used in P. aeruginosa QS inhibition to combat bacterial infections.

scholarly journals Natural Product Compounds in Alpinia officinarum and Ginger are Potent SARS-CoV-2 Papain-like Protease Inhibitors

2020 ◽  
Author(s):  
Dibakar Goswami ◽  
Mukesh Kumar ◽  
Sunil K. Ghosh ◽  
Amit Das
Keyword(s):  
Virtual Screening ◽  
Natural Product ◽  
Protease Inhibitors ◽  
In Silico ◽  
Drug Target ◽  
Homology Modelling ◽  
Protease Domain ◽  
Lead Compounds ◽  
Alpinia Officinarum ◽  
Natural Product Compounds

SARS-CoV-2 or COVID-19 has caused more than 10,00,000 infections and ~55,000 deaths worldwide spanning over 203 countries, and the numbers are exponentially increasing. Due to urgent need of treating the SARS infection, many approved, pre-clinical, anti-viral, anti-malarial and anti-SARS drugs are being administered to patients. SARS-CoV-2 papain-like protease (PLpro) has a protease domain which cleaves the viral polyproteins a/b, necessary for its survival and replication, and is one of the drug target against SARS-CoV-2. 3D structures of SARS-CoV-2 PLpro were built by homology modelling. Two models having partially open and closed conformations were used in our study. Virtual screening of natural product compounds was performed. We prepared an in house library of compounds found in rhizomes, Alpinia officinarum, ginger and curcuma, and docked them into the solvent accessible S3-S4 pocket of PLpro. Eight compounds from Alpinia officinarum and ginger bind with high in silico affinity to closed PLpro conformer, and hence are potential SARS-CoV-2 PLpro inhibitors. Our study reveal new lead compounds targeting SARS-CoV-2. Further structure based modifications or extract formulations of these compounds can lead to highly potent inhibitors to treat SARS-CoV-2 infections.<br>

scholarly journals Natural Product Compounds in Alpinia officinarum and Ginger are Potent SARS-CoV-2 Papain-like Protease Inhibitors

2020 ◽  
Author(s):  
Dibakar Goswami ◽  
Mukesh Kumar ◽  
Sunil K. Ghosh ◽  
Amit Das
Keyword(s):  
Virtual Screening ◽  
Natural Product ◽  
Protease Inhibitors ◽  
In Silico ◽  
Drug Target ◽  
Homology Modelling ◽  
Protease Domain ◽  
Lead Compounds ◽  
Alpinia Officinarum ◽  
Natural Product Compounds

SARS-CoV-2 or COVID-19 has caused more than 10,00,000 infections and ~55,000 deaths worldwide spanning over 203 countries, and the numbers are exponentially increasing. Due to urgent need of treating the SARS infection, many approved, pre-clinical, anti-viral, anti-malarial and anti-SARS drugs are being administered to patients. SARS-CoV-2 papain-like protease (PLpro) has a protease domain which cleaves the viral polyproteins a/b, necessary for its survival and replication, and is one of the drug target against SARS-CoV-2. 3D structures of SARS-CoV-2 PLpro were built by homology modelling. Two models having partially open and closed conformations were used in our study. Virtual screening of natural product compounds was performed. We prepared an in house library of compounds found in rhizomes, Alpinia officinarum, ginger and curcuma, and docked them into the solvent accessible S3-S4 pocket of PLpro. Eight compounds from Alpinia officinarum and ginger bind with high in silico affinity to closed PLpro conformer, and hence are potential SARS-CoV-2 PLpro inhibitors. Our study reveal new lead compounds targeting SARS-CoV-2. Further structure based modifications or extract formulations of these compounds can lead to highly potent inhibitors to treat SARS-CoV-2 infections.<br>

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