IN SILICO ANTIMALARIAL TARGET SELECTION CONSERVED IN FOUR PLASMODIUM SPECIES

Universal Journal of Pharmaceutical Research ◽

10.22270/ujpr.v5i5.483 ◽

2020 ◽

Author(s):

Oladoja AWofisayo

Keyword(s):

Comparative Genomics ◽

Peer Review ◽

In Silico ◽

Drug Targets ◽

Homo Sapiens ◽

Mammalian Species ◽

Target Selection ◽

Plasmodium Species ◽

Data Bank ◽

Sequence Motifs

Objectives: The need for new antimalarials drugs and drug targets is pertinent due to the emergence of drug resistant strains of the parasites. Improper target selection has resulted in therapeutic failure. The genomic/post genomic era has made possible the deciphering of the 3D crystal structures of proteins and DNA which are drug targets and are deposited in the protein data bank. Methods: Novel antimalarial targets obtained from evolutionary conserved short sequence motifs are utilised and are essential in transcription processes in the parasite. The motifs TGCATGCA, GTGCAC and GTGCGTGC were curated from experimental work, validated and analysed via phylogenomics genomics and comparative genomics. PlasmoDB blastn was applied to determine their similarity in Plasmodium vivax, knowlesi, Ovale and yoeli. The complete genome of Plasmodium falciparum vivax, knowlesi, Ovale and yoeli was downloaded from the plasmoDB and their positions determined. Results: The targets are essential, conserved in rodent and mammalian species via phylogenomics with percentage identity and similarity greater than 80%, have no similar genes in the same genome and also found to be selective in the parasites vis-à-vis the Homo sapiens via comparative genomics with 0% identity and similarity in the human genome. Conclusion: The targets reveal at the molecular and biochemical level, the vulnerable regions in the parasite while safe in human hence their choices in subsequent rationale drug discovery and design protocols. Peer Review History: Received: 18 July 2020; Revised: 1 October; Accepted: 12 October, Available online: 15 November 2020 UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file Average Peer review marks at initial stage: 5.5/10 Average Peer review marks at publication stage: 7.0/10 Reviewer(s) detail: Dr. Tamer ELHABIBI, ERU University, Egypt, [email protected] Dr. Soroush Sardari, Biotech Pasteur Institute of Iran, Tehran, Iran, [email protected] Comments of reviewer(s): Similar Articles: IN SILICO LIGAND-BASED 2D PHARMACOPHORE GENERATION FOR H+/K+ ATPASE INHIBITORS

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Potential Drug Target Identification in Porphyromonas gingivalis using In-silico Subtractive Metabolic Pathway Analysis

Bangladesh Journal of Medical Science ◽

10.3329/bjms.v20i4.54149 ◽

2021 ◽

Vol 20 (4) ◽

pp. 887-896

Author(s):

Prachi Sao ◽

Yamini Chand ◽

Atul Kumar ◽

Sachidanand Singh

Keyword(s):

Porphyromonas Gingivalis ◽

Pathway Analysis ◽

In Silico ◽

Drug Targets ◽

Homo Sapiens ◽

Medical Science ◽

Bone Destruction ◽

Therapeutic Drug ◽

Potential Drug ◽

Narrow Spectrum

Introduction: Porphyromonas Gingivalis (P. gingivalis) a primary periodontal disease pathogen. This bacterium affects sub-gingival tissue and leads to loss of teeth and alveolar bone destruction in the acute stage. In recent years, P. gingivalis is often connected with other diseases such as rheumatoid arthritis, diabetes, Alzheimer’s, and heart disease, though the aetiology is still unclear. Objective: The use of commonly available drugs to treat periodontitis results in various side effects, in particular multi-drug resistant strains. As the development of multidrugresistant strains frequently urges the identification of novel drug targets, the aim of this study is to identify specific targets in the narrow spectrum to combat oral pathogens. Methodology: This study used a comparative and subtractive pathway analysis approach to identify potential drug targets specific to P. gingivalis. Results: The in-silico comparison of the P. gingivalis and Homo sapiens (H. sapiens) metabolic pathways resulted in 13 unique pathogen pathways. A homology search of the 67 enzymes in the unique bacterial pathway using the BLASTp program against the Homo sapiens proteome resulted in fifteen possible targets that are non-homologous to the human proteome. Thirteen genes among 15 potent target encoders are key DEG genes indispensable for P. gingivalis’s survival. A comprehensive analysis of the literature identified three potential therapeutic drug targets. Conclusions: The three most relevant drug targets are Arabinose-5-phosphate isomerase, UDP-2,3-diacylglucosamine hydrolase, and Undecaprenyl diphosphatase. Upon corroboration, these targets may give rise to narrow-spectrum antibiotics that can specificallytreat thedental infection. Bangladesh Journal of Medical Science Vol.20(4) 2021 p.887-896

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Mycobacterium tuberculosis H37Rv: In Silico Drug Targets Identification by Metabolic Pathways Analysis

International Journal of Evolutionary Biology ◽

10.1155/2014/284170 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 13

Author(s):

Asad Amir ◽

Khyati Rana ◽

Arvind Arya ◽

Neelesh Kapoor ◽

Hirdesh Kumar ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

In Silico ◽

Metabolic Pathways ◽

Drug Targets ◽

Pathogenic Bacteria ◽

Homo Sapiens ◽

Protein Sequences ◽

Mycobacterium Tuberculosis H37rv ◽

Drug Molecules ◽

Pathways Analysis

Mycobacterium tuberculosis (Mtb) is a pathogenic bacteria species in the genus Mycobacterium and the causative agent of most cases of tuberculosis. Tuberculosis (TB) is the leading cause of death in the world from a bacterial infectious disease. This antibiotic resistance strain lead to development of the new antibiotics or drug molecules which can kill or suppress the growth of Mycobacterium tuberculosis. We have performed an in silico comparative analysis of metabolic pathways of the host Homo sapiens and the pathogen Mycobacterium tuberculosis (H37Rv). Novel efforts in developing drugs that target the intracellular metabolism of M. tuberculosis often focus on metabolic pathways that are specific to M. tuberculosis. We have identified five unique pathways for Mycobacterium tuberculosis having a number of 60 enzymes, which are nonhomologous to Homo sapiens protein sequences, and among them there were 55 enzymes, which are nonhomologous to Homo sapiens protein sequences. These enzymes were also found to be essential for survival of the Mycobacterium tuberculosis according to the DEG database. Further, the functional analysis using Uniprot showed involvement of all the unique enzymes in the different cellular components.

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IN SILICO IDENTIFICATION OF TARGET PALINDROMIC GENES AS POTENTIAL DRUG TARGETS IN BREAST CANCER THERAPY

Universal Journal of Pharmaceutical Research ◽

10.22270/ujpr.v5i5.478 ◽

2020 ◽

Author(s):

Oladoja Awofisayo

Keyword(s):

Breast Cancer ◽

Cancer Therapy ◽

Peer Review ◽

In Silico ◽

Drug Targets ◽

Health Concern ◽

Potential Drug ◽

Breast Cancer Therapy ◽

Base Pairs ◽

Potential Drug Targets

Objectives: Diabetes is increasingly recognized as a serious, worldwide public health concern. By early identifying those at risk to develop diabetes and if confirmed to be at pre-diabetes stage adequate care provided for them through lifestyle interventions or even hypoglycemic medications if necessary, thus delaying or preventing their progression to diabetic status. The study aims at assessing the risk of developing type 2 diabetes mellitus (T2DM) among healthy non-diabetic Sudanese in Khartoum city. Breast cancer (BC) is the most common cancer worldwide prevalent among women with more than one million cases and is second only to lung cancer. Methods: The identification of the sequences based on the unique tetramers GCAC, GTCA were selected from experimental work. The16 base pair DNA regulatory sequences of which the motifs area part of containing these motif in genes implicated in cancer CAGE1 (AAGCTGTCATTA), BRCA1(GACTGAGTCAA), ABCB1(CTCTAAGTCAT), ABCB5 (GATATGTTAAAGC) and ABI1(CTTCTGGGAA) were then selected as novel putative targets in breast cancer therapy based on their selectivity on the BC oncogenes which are not found in the normal human genome 1-23 and the sex chromosomes X and Y were obtained via computational analysis. Results: The single copy base pairs which will be potential drug targets as anticancer drugs were finally obtained as CTGTTATGACTGAGTCAA, CAGE1 with the 17 base pairs CATAAAAGC TGTCATTA and ABCB1 TTGCCAA CTCTAAGT CAT. Conclusion: It is Possible that the in silico discovery of putative anti breast cancer targets of importance in the genome. Peer Review History: Received 18 July 2020; Revised 25 September; Accepted 12 October, Available online 15 November 2020 UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file Average Peer review marks at initial stage: 5.5/10 Average Peer review marks at publication stage: 7.0/10 Reviewer(s) detail: Dr. Nkechi Obiofu Ezenobi, University of Port Harcourt, Nigeria, [email protected] Shahinga Vanji, World Academy of Medical Sciences, Iran, [email protected] Comments of reviewer(s): Similar Articles: IN SILICO LIGAND-BASED 2D PHARMACOPHORE GENERATION FOR H+/K+ ATPASE INHIBITORS

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http://www.biotech-asia.org/vol18no2/in-silico-modelling-of-1-3-3-substituted-phenyl-prop-2-enoyl-phenyl-thiourea-against-anti-inflammatory-drug-targets/

Biosciences Biotechnology Research Asia ◽

10.13005/bbra/2928 ◽

2021 ◽

Vol 18 (2) ◽

pp. 413-421

Author(s):

Sounok Sengupta ◽

Ratul Bhowmik ◽

Satarupa Acharjee ◽

Suchandra Sen

Keyword(s):

Binding Affinity ◽

In Silico ◽

Drug Targets ◽

Interleukin 1 ◽

Md Simulations ◽

Data Bank ◽

Ligand Molecule ◽

Toxicity Analysis ◽

Anti Inflammatory ◽

Oxide Synthase

The main objective of this present study was to analyze the anti-inflammatory activity of the compound 1- 3- [3-(substituted phenyl) prop-2-enoyl) phenyl thiourea against inflammation receptors Secretory Phospholipase A2 (sPLA2-X), Cyclooxygenase-2 (COX-2), Interleukin-1 Receptor-associated Kinase 4 (IRAK4), Tumor Necrosis Factor (TNF-alpha) and Inducible Nitric Oxide Synthase 4 using various in-silico techniques. The 3D structures of the receptors were retrieved from Protein Data Bank in PDB format. The ligand molecule was sketched in Chemdraw Ultra v 10.0. The proteins and the ligand molecule were then individually prepared for docking using AutoDock Tools. Docking was performed using AutoDock Vina. Swiss-ADME and Pre-ADMET web servers were used for ADME, drug-likeness, and toxicity analysis. The receptor showing the best binding affinity with our ligand molecule was further analyzed via Molecular Dynamics (MD) Simulations using iMODS web server. The docking results revealed that our ligand molecule showed the best binding affinity with receptor sPLA2-X. The ADME analysis results of our ligand molecule were also good. MD Simulations study showed good results with our ligand- sPLA2-X receptor docked complex. This study revealed that our ligand molecule is a significant inhibitor sPLA2-X and can be further used as a potential therapy against inflammatory disorders.

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Comparative Study on Mitogen Activated Protein Kinase of Plasmodium Species by Using in silico Method

Scientific Research Journal ◽

10.24191/srj.v9i1.9411 ◽

2012 ◽

Vol 9 (1) ◽

pp. 1

Author(s):

Mohd Fakharul Zaman Raja Yahya ◽

Hasidah Mohd Sidek

Keyword(s):

Amino Acid ◽

In Silico ◽

Nuclear Export ◽

Nuclear Export Signal ◽

Plasmodium Species ◽

Mitogen Activated Protein Kinase ◽

Multiple Sequence ◽

Wide Range ◽

Mitogen Activated Protein ◽

Human Plasmodium

Malaria parasites, Plasmodium can infect a wide range of hosts including humans and rodents. There are two copies of mitogen activated protein kinases (MAPKs) in Plasmodium, namely MAPK1 and MAPK2. The MAPKs have been studied extensively in the human Plasmodium, P. falciparum. However, the MAPKs from other Plasmodium species have not been characterized and it is therefore the premise of presented study to characterize the MAPKs from other Plasmodium species-P. vivax, P. knowlesi, P. berghei, P. chabaudi and P.yoelli using a series of publicly available bioinformatic tools. In silico data indicates that all Plasmodium MAPKs are nuclear-localized and contain both a nuclear localization signal (NLS) and a Leucine-rich nuclear export signal (NES). The activation motifs of TDY and TSH were found to be fully conserved in Plasmodium MAPK1 and MAPK2, respectively. The detailed manual inspection of a multiple sequence alignment (MSA) construct revealed a total of 17 amino acid stack patterns comprising of different amino acids present in MAPKJ and MAPK2 respectively, with respect to rodent and human Plasmodia. It is proposed that these amino acid stack patterns may be useful in explaining the disparity between rodent and human Plasmodium MAPKs.

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Comparative Study on Mitogen Activated Protein Kinase of Plasmodium Species by Using In silico Method

Scientific Research Journal ◽

10.24191/srj.v9i1.5052 ◽

2012 ◽

Vol 9 (1) ◽

pp. 1

Author(s):

Mohd Fakharul Zaman Raja Yahya ◽

Hasidah Mohd Sidek

Keyword(s):

Amino Acid ◽

In Silico ◽

Nuclear Export ◽

Nuclear Export Signal ◽

Plasmodium Species ◽

Mitogen Activated Protein Kinase ◽

Multiple Sequence ◽

Bioinformatic Tools ◽

Wide Range ◽

Human Plasmodium

Malaria parasites, Plasmodium can infect a wide range ofhosts including humans and rodents. There are two copies ofmitogen activated protein kinases (MAPKs) in Plasmodium, namely MAPK1 and MAPK2. The MAPKs have been studied extensively in the human Plasmodium, P. falciparum. However, the MAPKs from other Plasmodium species have not been characterized and it is therefore the premise ofpresented study to characterize the MAPKs from other Plasmodium species-P. vivax, P. knowlesi, P. berghei, P. chabaudi and P.yoelli using a series ofpublicly available bioinformatic tools. In silico data indicates that all Plasmodium MAPKs are nuclear-localizedandcontain both a nuclear localization signal (NLS) anda Leucine-rich nuclear export signal (NES). The activation motifs ofTDYand TSH werefound to befully conserved in Plasmodium MAPK1 and MAPK2, respectively. The detailed manual inspection ofa multiple sequence alignment (MSA) construct revealed a total of 17 amino acid stack patterns comprising ofdifferent amino acids present in MAPK1 and MAPK2 respectively, with respect to rodent and human Plasmodia. 1t is proposed that these amino acid stack patterns may be useful in explaining the disparity between rodent and human Plasmodium MAPKs.

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In silico Discovery of Resveratrol Analogues as Potential Agents in Treatment of Metabolic Disorders

Current Pharmaceutical Design ◽

10.2174/1381612825666191029095252 ◽

2019 ◽

Vol 25 (35) ◽

pp. 3776-3783

Author(s):

Nebojša Pavlović ◽

Maja Đanić ◽

Bojan Stanimirov ◽

Svetlana Goločorbin-Kon ◽

Karmen Stankov ◽

...

Keyword(s):

In Silico ◽

Metabolic Disorders ◽

Partial Agonist ◽

Aqueous Solubility ◽

Structural Similarity ◽

Data Bank ◽

Docking Studies ◽

Binding Energies ◽

Molegro Virtual Docker ◽

Ppar Γ

Background: Resveratrol was demonstrated to act as partial agonist of PPAR-γ receptor, which opens up the possibility for its use in the treatment of metabolic disorders. Considering the poor bioavailability of resveratrol, particularly due to its low aqueous solubility, we aimed to identify analogues of resveratrol with improved pharmacokinetic properties and higher binding affinities towards PPAR-γ. Methods: 3D structures of resveratrol and its analogues were retrieved from ZINC database, while PPAR-γ structure was obtained from Protein Data Bank. Docking studies were performed using Molegro Virtual Docker software. Molecular descriptors relevant to pharmacokinetics were calculated from ligand structures using VolSurf+ software. Results: Using structural similarity search method, 56 analogues of resveratrol were identified and subjected to docking analyses. Binding energies were ranged from -136.69 to -90.89 kcal/mol, with 16 analogues having higher affinities towards PPAR-γ in comparison to resveratrol. From the calculated values of SOLY descriptor, 23 studied compounds were shown to be more soluble in water than resveratrol. However, only two tetrahydroxy stilbene derivatives, piceatannol and oxyresveratrol, had both better solubility and affinity towards PPAR-γ. These compounds also had more favorable ADME profile, since they were shown to be more metabolically stable and wider distributed in body than resveratrol. Conclusion: Piceatannol and oxyresveratrol should be considered as potential lead compounds for further drug development. Although experimental validation of obtained in silico results is required, this work can be considered as a step toward the discovery of new natural and safe drugs in treatment of metabolic disorders.

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Phytochemicals for drug discovery in Alzheimer’s disease: In silico Advances

Current Pharmaceutical Design ◽

10.2174/1381612826666200928161721 ◽

2020 ◽

Vol 26 ◽

Author(s):

Smriti Sharma ◽

Vinayak Bhatia

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Drug Design ◽

In Silico ◽

Drug Targets ◽

Development Process ◽

Phytochemical Analysis ◽

Computational Drug Design ◽

Novel Drugs ◽

Game Changer

: The search for novel drugs that can prevent or control Alzheimer’s disease has attracted lot of attention from researchers across the globe. Phytochemicals are increasingly being used to provide scaffolds to design drugs for AD. In silico techniques, have proven to be a game-changer in this drug design and development process. In this review, the authors have focussed on current advances in the field of in silico medicine, applied to phytochemicals, to discover novel drugs to prevent or cure AD. After giving a brief context of the etiology and available drug targets for AD, authors have discussed the latest advances and techniques in computational drug design of AD from phytochemicals. Some of the prototypical studies in this area are discussed in detail. In silico phytochemical analysis is a tool of choice for researchers all across the globe and helps integrate chemical biology with drug design.

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Virtual Screening, Molecular docking and in-silico ADME-Tox analysis for identification of potential main protease (Mpro) enzyme inhibitors

Anti-Infective Agents ◽

10.2174/2211352518999201208201854 ◽

2020 ◽

Vol 18 ◽

Author(s):

Debadash Panigrahi ◽

Ganesh Prasad Mishra

Keyword(s):

Molecular Docking ◽

Virtual Screening ◽

In Silico ◽

Data Bank ◽

Future Research ◽

Reference Compound ◽

Unexpected Death ◽

Main Protease ◽

In Silico Admet

Objective:: Recent pandemic caused by SARS-CoV-2 described in Wuhan China in December-2019 spread widely almost all the countries of the world. Corona virus (COVID-19) is causing the unexpected death of many peoples and severe economic loss in several countries. Virtual screening based on molecular docking, drug-likeness prediction, and in silico ADMET study has become an effective tool for the identification of small molecules as novel antiviral drugs to treat diseases. Methods:: In the current study, virtual screening was performed through molecular docking for identifying potent inhibitors against Mpro enzyme from the ZINC library for the possible treatment of COVID-19 pandemic. Interestingly, some compounds are identified as possible anti-covid-19 agents for future research. 350 compounds were screened based on their similarity score with reference compound X77 from ZINC data bank and were subjected to docking with crystal structure available of Mpro enzyme. These compounds were then filtered by their in silico ADME-Tox and drug-likeness prediction values. Result:: Out of these 350 screened compounds, 10 compounds were selected based on their docking score and best docked pose in comparison to the reference compound X77. In silico ADME-Tox and drug likeliness predictions of the top compounds were performed and found to be excellent results. All the 10 screened compounds showed significant binding pose with the target enzyme main protease (Mpro) enzyme and satisfactory pharmacokinetic and toxicological properties. Conclusion:: Based on results we can suggest that the identified compounds may be considered for therapeutic development against the COVID-19 virus and can be further evaluated for in vitro activity, preclinical, clinical studies and formulated in a suitable dosage form to maximize their bioavailability.

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