Dataset Information

Finding candidate drugs for hepatitis C based on chemical-chemical and chemical-protein interactions.

ABSTRACT: Hepatitis C virus (HCV) is an infectious virus that can cause serious illnesses. Only a few drugs have been reported to effectively treat hepatitis C. To have greater diversity in drug choice and better treatment options, it is necessary to develop more drugs to treat the infection. However, it is time-consuming and expensive to discover candidate drugs using experimental methods, and computational methods may complement experimental approaches as a preliminary filtering process. This type of approach was proposed by using known chemical-chemical interactions to extract interactive compounds with three known drug compounds of HCV, and the probabilities of these drug compounds being able to treat hepatitis C were calculated using chemical-protein interactions between the interactive compounds and HCV target genes. Moreover, the randomization test and expectation-maximization (EM) algorithm were both employed to exclude false discoveries. Analysis of the selected compounds, including acyclovir and ganciclovir, indicated that some of these compounds had potential to treat the HCV. Hopefully, this proposed method could provide new insights into the discovery of candidate drugs for the treatment of HCV and other diseases.

SUBMITTER: Chen L

PROVIDER: S-EPMC4166673 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Finding candidate drugs for hepatitis C based on chemical-chemical and chemical-protein interactions.

Chen Lei L Lu Jing J Huang Tao T Yin Jun J Wei Lai L Cai Yu-Dong YD

PloS one 20140916 9

Hepatitis C virus (HCV) is an infectious virus that can cause serious illnesses. Only a few drugs have been reported to effectively treat hepatitis C. To have greater diversity in drug choice and better treatment options, it is necessary to develop more drugs to treat the infection. However, it is time-consuming and expensive to discover candidate drugs using experimental methods, and computational methods may complement experimental approaches as a preliminary filtering process. This type of ap ...[more]

PMID: 25225900

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Project description:BackgroundThe coronavirus disease-19 (COVID-19) emerged in Wuhan, China and rapidly spread worldwide. Researchers are trying to find a way to treat this disease as soon as possible. The present study aimed to identify the genes involved in COVID-19 and find a new drug target therapy. Currently, there are no effective drugs targeting SARS-CoV-2, and meanwhile, drug discovery approaches are time-consuming and costly. To address this challenge, this study utilized a network-based drug repurposing strategy to rapidly identify potential drugs targeting SARS-CoV-2. To this end, seven potential drugs were proposed for COVID-19 treatment using protein-protein interaction (PPI) network analysis. First, 524 proteins in humans that have interaction with the SARS-CoV-2 virus were collected, and then the PPI network was reconstructed for these collected proteins. Next, the target miRNAs of the mentioned module genes were separately obtained from the miRWalk 2.0 database because of the important role of miRNAs in biological processes and were reported as an important clue for future analysis. Finally, the list of the drugs targeting module genes was obtained from the DGIDb database, and the drug-gene network was separately reconstructed for the obtained protein modules.ResultsBased on the network analysis of the PPI network, seven clusters of proteins were specified as the complexes of proteins which are more associated with the SARS-CoV-2 virus. Moreover, seven therapeutic candidate drugs were identified to control gene regulation in COVID-19. PACLITAXEL, as the most potent therapeutic candidate drug and previously mentioned as a therapy for COVID-19, had four gene targets in two different modules. The other six candidate drugs, namely, BORTEZOMIB, CARBOPLATIN, CRIZOTINIB, CYTARABINE, DAUNORUBICIN, and VORINOSTAT, some of which were previously discovered to be efficient against COVID-19, had three gene targets in different modules. Eventually, CARBOPLATIN, CRIZOTINIB, and CYTARABINE drugs were found as novel potential drugs to be investigated as a therapy for COVID-19.ConclusionsOur computational strategy for predicting repurposable candidate drugs against COVID-19 provides efficacious and rapid results for therapeutic purposes. However, further experimental analysis and testing such as clinical applicability, toxicity, and experimental validations are required to reach a more accurate and improved treatment. Our proposed complexes of proteins and associated miRNAs, along with discovered candidate drugs might be a starting point for further analysis by other researchers in this urgency of the COVID-19 pandemic.

Project description:Given a compound, how can we effectively predict its biological function? It is a fundamentally important problem because the information thus obtained may benefit the understanding of many basic biological processes and provide useful clues for drug design. In this study, based on the information of chemical-chemical interactions, a novel method was developed that can be used to identify which of the following eleven metabolic pathway classes a query compound may be involved with: (1) Carbohydrate Metabolism, (2) Energy Metabolism, (3) Lipid Metabolism, (4) Nucleotide Metabolism, (5) Amino Acid Metabolism, (6) Metabolism of Other Amino Acids, (7) Glycan Biosynthesis and Metabolism, (8) Metabolism of Cofactors and Vitamins, (9) Metabolism of Terpenoids and Polyketides, (10) Biosynthesis of Other Secondary Metabolites, (11) Xenobiotics Biodegradation and Metabolism. It was observed that the overall success rate obtained by the method via the 5-fold cross-validation test on a benchmark dataset consisting of 3,137 compounds was 77.97%, which is much higher than 10.45%, the corresponding success rate obtained by the random guesses. Besides, to deal with the situation that some compounds may be involved with more than one metabolic pathway class, the method presented here is featured by the capacity able to provide a series of potential metabolic pathway classes ranked according to the descending order of their likelihood for each of the query compounds concerned. Furthermore, our method was also applied to predict 5,549 compounds whose metabolic pathway classes are unknown. Interestingly, the results thus obtained are quite consistent with the deductions from the reports by other investigators. It is anticipated that, with the continuous increase of the chemical-chemical interaction data, the current method will be further enhanced in its power and accuracy, so as to become a useful complementary vehicle in annotating uncharacterized compounds for their biological functions.

Dataset Information

Finding candidate drugs for hepatitis C based on chemical-chemical and chemical-protein interactions.

Publications

Finding candidate drugs for hepatitis C based on chemical-chemical and chemical-protein interactions.

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