scholarly journals Virtual Screening to Identify the Protein Network Interaction of Berberine with Red Complex Pathogens

2021 ◽  
pp. 645-652
Author(s):  
S. Abinaya ◽  
J. Vijayashree Priyadharsini ◽  
A. S. Smiline Girija ◽  
P. Sankar Ganesh
Keyword(s):  
Virtual Screening ◽  
Screening Method ◽  
Transcriptional Regulator ◽  
Subcellular Location ◽  
Protein Network ◽  
Bacterial Cells ◽  
Virulence Proteins ◽  
Peptide Epitopes ◽  
Network Interaction

Introduction: Periodontal disease is an infection of the tissues that hold your teeth in place. It's typically caused by poor brushing and flossing habits that allow plaque, a sticky film of bacteria, to build up on the teeth and harden. Elimination of these pathogens from the site of infection remains a perplexing task, which demands the use of antibiotics. The emergence of drug resistant forms has spurred interest into identifying novel therapeutic targets against these pathogens. Aim: The present study employs virtual screening method to identify the protein network interaction of berberine with red complex pathogens. Materials and Methods: Computational tools were used to identify the targets, assess their functional role and virulence property. Further, the peptide epitopes present in the virulence factors were identified using the BepiPred tool. The subcellular location of the virulence proteins was also elucidated using PSORTb. Results: Berberine was found to target vital protein transporters such as TetR family transcriptional regulator and MerR family transcriptional regulator, which is known to play a crucial role in the survival of bacterial cells. Conclusion: Hence the present study provides preliminary data on the protein targets of berberine against red complex pathogens. However, in vitro studies using the compound is warranted to further confirm the efficacy of the compound.

Targeting FGL2, a molecular drug target for glioblastoma, with natural compounds through virtual screening method

2021 ◽  
Author(s):  
Fahad Hassan Shah ◽  
Song Ja Kim
Keyword(s):  
Virtual Screening ◽  
Active Site ◽  
Drug Target ◽  
Screening Method ◽  
Tumor Development ◽  
Pharmacokinetic Profile ◽  
Natural Compounds ◽  
Screening Platform ◽  
Proliferation In Vitro

Background: Fibroleukin-2 protein (FGL2) causes redevelopment of brain tumors. Inhibition of these proteins has shown to improve glioblastoma prognosis and treatment efficacy. Aim: The current study gathered recently exploited natural compounds that suppress glioblastoma proliferation in vitro, tested against FGL2 protein. Method: Twenty-five compounds were explored through a virtual screening platform. Results: Three natural compounds (betanine, hesperetin and ovatodiolide) hit the active site of FGL2. Furthermore, the influence of these compounds was also assessed using in silico gene expression, and ADMET tools showed downregulation of some genes, which caused rapid tumor development while possessing a moderate acute toxicity and pharmacokinetic profile. Conclusion: Our study presents three compounds that are good candidates for evaluation in FGL2 mutated glioblastoma animal models.

scholarly journals Study on Structure Activity Relationship of Natural Flavonoids against Thrombin by Molecular Docking Virtual Screening Combined with Activity Evaluation In Vitro

Molecules ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 422
Author(s):  
Xiaoyan Wang ◽  
Zhen Yang ◽  
Feifei Su ◽  
Jin Li ◽  
Evans Owusu Boadi ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
Screening Method ◽  
Thrombin Inhibitors ◽  
Coagulation Cascade ◽  
Oh Groups ◽  
Structure Activity Relationships ◽  
Thrombin Inhibition ◽  
Structure Activity

Thrombin, a key enzyme of the serine protease superfamily, plays an integral role in the blood coagulation cascade and thrombotic diseases. In view of this, it is worthwhile to establish a method to screen thrombin inhibitors (such as natural flavonoid-type inhibitors) as well as investigate their structure activity relationships. Virtual screening using molecular docking technique was used to screen 103 flavonoids. Out of this number, 42 target compounds were selected, and their inhibitory effects on thrombin assayed by chromogenic substrate method. The results indicated that the carbon-carbon double bond group at the C2, C3 sites and the carbonyl group at the C4 sites of flavones were essential for thrombin inhibition, whereas the methoxy and O-glycosyl groups reduced thrombin inhibition. Noteworthy, introduction of OH groups at different positions on flavonoids either decreased or increased anti-thrombin potential. Myricetin exhibited the highest inhibitory potential against thrombin with an IC50 value of 56 μM. Purposively, the established molecular docking virtual screening method is not limited to exploring flavonoid structure activity relationships to anti-thrombin activity but also usefully discovering other natural active constituents.

scholarly journals Virtual Screening to Identify the Protein Network Interactions of Triclosan with Streptococcus mutans and Enterococcus faecalis

2021 ◽  
pp. 677-683
Author(s):  
T. K. Hariprasanth ◽  
J. Vijayashree Priyadharsini ◽  
A. S. Smiline Girija ◽  
P. Sankar Ganesh
Keyword(s):  
Virtual Screening ◽  
Streptococcus Mutans ◽  
Enterococcus Faecalis ◽  
Protein Interactions ◽  
Screening Method ◽  
Epitope Prediction ◽  
Antimicrobial Effect ◽  
Functional Class ◽  
Protein Network ◽  
Mouth Rinses

Introduction: Triclosan is considered to be an important ingredient in toothpastes and mouth rinses. Several studies have reported contradictory results regarding the antimicrobial effect of triclosan. Hence, the present in silico study intends to identify the potential targets of triclosan in two common dental pathogens Streptococcus mutans and Enterococcus faecalis. Aim: To identify the protein network interactions of triclosan in Streptococcus mutans and Enterococcus faecalis by virtual screening method. Materials and Methods: The STITCH v5.0 database was initially used for identifying drug-protein interactions followed by VICMPred and VirulentPred which was employed to identify functional class of the proteins and its virulence property. Finally, BepiPred v1.0 Linear Epitope Prediction tool was used to identify the potential epitopes of the virulent proteins. Results: Triclosan was found to interact with crucial proteins in S. mutans and E. faecalis which could contribute to severe forms of periodontitis and endodontic diseases. Conclusion: Taken together, the present study provides the preliminary data on the potential targets of triclosan in common dental pathogens. Further experimental validation is warranted to provide concrete evidence on the molecular targets of dental pathogens. 

scholarly journals An Observational Study on the Mode of Action of Ferulic Acid on Common Dental Pathogens – An in Silico Approach

2020 ◽  
pp. 13-20
Author(s):  
R. Nivethitha ◽  
A. S. Smiline Girija ◽  
J. Vijayashree Priyadharsini
Keyword(s):  
Ferulic Acid ◽  
Streptococcus Mutans ◽  
In Silico ◽  
Subcellular Location ◽  
Functional Class ◽  
Protein Targets ◽  
Peptide Epitopes ◽  
Phosphogluconate Dehydrogenase

In this study, the functional and virulent classes of proteins that are targeted by ferulic acid are identified from the most common dental pathogens like Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, Streptococcus mutans and Enterococcus faecalis by an in silico approach. The target proteins were selected using STITCH tool, the functional class of proteins was predicted using VICMpred. The predicted virulent proteins were further subjected to BepiPred analysis, which returned the number of peptide epitopes present in the protein. Further, the subcellular location of the proteins was confirmed by the PSORTb tool. Ferulic acid was found to interact with virulence factors such as dihydrolipoyl dehydrogenase of Streptococcus mutans, putative lipoprotein of P. gingivalis and phosphogluconate dehydrogenase of T. forsythia. The findings of the study emphasize the promising interactive role of ferulic acid and their potential protein targets in common oro-dental pathogens which requires further experimental validation in-vivo and in-vitro.

Design, Synthesis and Biological Evaluation of Uracil Derivatives as Novel VEGFR-2 Inhibitors

2018 ◽  
Vol 24 (6) ◽  
pp. 734-740 ◽  
Author(s):  
Jingwei Liang ◽  
Xinyang Li ◽  
Su Yang ◽  
Xin He ◽  
Mingyang Wang ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Screening Method ◽  
Growth Factor Receptor ◽  
Biological Evaluation ◽  
Type I ◽  
Lead Compound ◽  
Design Synthesis ◽  
Uracil Derivatives ◽  
Inhibitory Activities

Backgound: Vascular endothelial growth factor receptor-2 (VEGFR-2) plays a crucial role in the process of cancer angiogenesis. Type I inhibitors constitute the major ATP-competitive inhibitors and recognize mainly the active conformation of VEGFR-2. Meanwhile, type II inhibitors recognize the inactive DFG (Asp- Phe-Gly)-out conformation of VEGFR-2, which was a more promising approach for drug intervention. Methods: According to the lead compound of uracil skeleton, being screened out by structure-based virtual screening, a series of uracil derivatives were designed and synthesized. Results: The inhibitory activities were investigated against VEGFR-2 kinase in vitro. The results turned out that series A performed moderate inhibitory activities, especially compound A4 exhibited the most potent inhibitory activity (IC50=0.029 µM). Conclusion: The lead compound was screened out by structure-based pharmacophore models, then two series of uracil derivatives were synthesized according to it and evaluated for their inhibitory activities against VEGFR-2. In this study, not only a potential inhibitor has been discovered, it also demonstrates the feasibility of structure-based virtual screening method for drug discovery.

An integrated screening method for evaluating the pulmonary toxicity of inhaled particulates: Role of microscopic techniques in assessing pulmonary macrophage clearance functions

1990 ◽  
Vol 48 (3) ◽  
pp. 826-827
Author(s):  
David B. Warheit ◽  
Lena Achinko ◽  
Mark A. Hartsky
Keyword(s):  
Bronchoalveolar Lavage ◽  
Pulmonary Toxicity ◽  
Screening Method ◽  
Pulmonary Response ◽  
Inhaled Particles ◽  
Cytochemical Analysis ◽  
Pulmonary Macrophages ◽  
Integrated Screening

There is a great need for the development of a rapid and reliable bioassay to evaluate the pulmonary toxicity of inhaled particles. A number of methods have been proposed, including lung clearance studies, bronchoalveolar lavage analysis, and in vitro cytotoxicity tests. These methods are often limited in scope inasmuch as they measure only one dimension of the pulmonary response to inhaled, instilled or incubated dusts. Accordingly, a comprehensive approach to lung toxicity studies has been developed.To validate the method, rats were exposed for 6 hours or 3 days to various concentrations of either aerosolized alpha quartz silica (Si) or carbonyl iron (CI) particles. Cells and fluids from groups of sham and dust-exposed animals were recovered by bronchoalveolar lavage (BAL). Alkaline phosphatase, LDH and protein values were measured in BAL fluids at several time points postexposure. Cells were counted and evaluated for viability, as well as differential and cytochemical analysis. In addition, pulmonary macrophages (PM) were cultured and studied for morphology, chemotaxis, and phagocytosis by scanning electron microscopy.

Mechanisms involved in effects of antimicrobial peptides, bactenectins ChBac3.4, ChBac5, and mini-ChBac7.5Nb, on bacterial cells

2017 ◽  
pp. 43-50
Author(s):  
О.В. Шамова ◽  
М.С. Жаркова ◽  
П.М. Копейкин ◽  
Д.С. Орлов ◽  
Е.А. Корнева
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Activity ◽  
Innate Immunity ◽  
Infectious Diseases ◽  
Metabolic Activity ◽  
Capra Hircus ◽  
Bacterial Cells ◽  
Antibiotic Resistant ◽  
Resistant Strains

Антимикробные пептиды (АМП) системы врожденного иммунитета - соединения, играющие важную роль в патогенезе инфекционных заболеваний, так как обладают свойством инактивировать широкий спектр патогенных бактерий, обеспечивая противомикробную защиту живых организмов. В настоящее время АМП рассматриваются как потенциальные соединения-корректоры инфекционной патологии, вызываемой антибиотикорезистентными бактериями (АБР). Цель данной работы состояла в изученим механизмов антибактериального действия трех пептидов, принадлежащих к семейству бактенецинов - ChBac3.4, ChBac5 и mini-ChBac7.5Nb. Эти химически синтезированные пептиды являются аналогами природных пролин-богатых АМП, обнаруженных в лейкоцитах домашней козы Capra hircus и проявляющих высокую антимикробную активность, в том числе и в отношении грамотрицательных АБР. Методы. Минимальные ингибирующие и минимальные бактерицидные концентрации пептидов (МИК и МБК) определяли методом серийных разведений в жидкой питательной среде с последующим высевом на плотную питательную среду. Эффекты пептидов на проницаемость цитоплазматической мембраны бактерий для хромогенного маркера исследовали с использованием генетически модифицированного штамма Escherichia coli ML35p. Действие бактенецинов на метаболическую активность бактерий изучали с применением маркера резазурина. Результаты. Показано, что все исследованные пептиды проявляют высокую антимикробную активность в отношении Escherichia coli ML35p и антибиотикоустойчивых штаммов Escherichia coli ESBL и Acinetobacter baumannii in vitro, но их действие на бактериальные клетки разное. Использован комплекс методик, позволяющих наблюдать в режиме реального времени динамику действия бактенецинов в различных концентрациях (включая их МИК и МБК) на барьерную функцию цитоплазматической мембраны и на интенсивность метаболизма бактериальных клеток, что дало возможность выявить различия в характере воздействия бактенецинов, отличающихся по структуре молекулы, на исследуемые микроорганизмы. Установлено, что действие каждого из трех исследованных бактенецинов в бактерицидных концентрациях отличается по эффективности нарушения целостности бактериальных мембран и в скорости подавления метаболизма клеток. Заключение. Полученная информация дополнит существующие фундаментальные представления о механизмах действия пролин-богатых пептидов врожденного иммунитета, а также послужит основой для биотехнологических исследований, направленных на разработку на базе этих соединений новых антибиотических препаратов для коррекции инфекционных заболеваний, вызываемых АБР и являющимися причинами тяжелых внутрибольничных инфекций. Antimicrobial peptides (AMPs) of the innate immunity are compounds that play an important role in pathogenesis of infectious diseases due to their ability to inactivate a broad array of pathogenic bacteria, thereby providing anti-microbial host defense. AMPs are currently considered promising compounds for treatment of infectious diseases caused by antibiotic-resistant bacteria. The aim of this study was to investigate molecular mechanisms of the antibacterial action of three peptides from the bactenecin family, ChBac3.4, ChBac5, and mini-ChBac7.5Nb. These chemically synthesized peptides are analogues of natural proline-rich AMPs previously discovered by the authors of the present study in leukocytes of the domestic goat, Capra hircus. These peptides exhibit a high antimicrobial activity, in particular, against antibiotic-resistant gram-negative bacteria. Methods. Minimum inhibitory and minimum bactericidal concentrations of the peptides (MIC and MBC) were determined using the broth microdilution assay followed by subculturing on agar plates. Effects of the AMPs on bacterial cytoplasmic membrane permeability for a chromogenic marker were explored using a genetically modified strain, Escherichia coli ML35p. The effect of bactenecins on bacterial metabolic activity was studied using a resazurin marker. Results. All the studied peptides showed a high in vitro antimicrobial activity against Escherichia coli ML35p and antibiotic-resistant strains, Escherichia coli ESBL and Acinetobacter baumannii, but differed in features of their action on bacterial cells. The used combination of techniques allowed the real-time monitoring of effects of bactenecin at different concentrations (including their MIC and MBC) on the cell membrane barrier function and metabolic activity of bacteria. The differences in effects of these three structurally different bactenecins on the studied microorganisms implied that these peptides at bactericidal concentrations differed in their capability for disintegrating bacterial cell membranes and rate of inhibiting bacterial metabolism. Conclusion. The obtained information will supplement the existing basic concepts on mechanisms involved in effects of proline-rich peptides of the innate immunity. This information will also stimulate biotechnological research aimed at development of new antibiotics for treatment of infectious diseases, such as severe in-hospital infections, caused by antibiotic-resistant strains.

Discovery of New AKT1 Inhibitors by Combination of In silico Structure Based Virtual Screening Approaches and Biological Evaluations

2019 ◽  
Author(s):  
Filip Fratev ◽  
Denisse A. Gutierrez ◽  
Renato J. Aguilera ◽  
suman sirimulla
Keyword(s):  
Virtual Screening ◽  
Success Rate ◽  
Protein Interactions ◽  
In Silico ◽  
Biological Data ◽  
In Vitro Binding ◽  
Vitro Binding ◽  
Screening Protocol ◽  
Screening Approaches

AKT1 is emerging as a useful target for treating cancer. Herein, we discovered a new set of ligands that inhibit the AKT1, as shown by in vitro binding and cell line studies, using a newly designed virtual screening protocol that combines structure-based pharmacophore and docking screens. Taking together with the biological data, the combination of structure based pharamcophore and docking methods demonstrated reasonable success rate in identifying new inhibitors (60-70%) proving the success of aforementioned approach. A detail analysis of the ligand-protein interactions was performed explaining observed activities.<br>

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