Network bioinformatics analysis provides insight into drug repurposing for COVID-19

The COVID-2019 disease caused by the SARS-CoV-2 virus (aka 2019-nCoV) has raised significant health concerns in China and worldwide. While novel drug discovery and vaccine studies are long, repurposing old drugs against the COVID-2019 epidemic can help identify treatments, with known preclinical, pharmacokinetic, pharmacodynamic, and toxicity profiles, which can rapidly enter Phase 3 or 4 or can be used directly in clinical settings. In this study, we presented a novel network based drug repurposing platform to identify potential drugs for the treatment of COVID-2019. We first analysed the genome sequence of SARS-CoV-2 and identified SARS as the closest disease, based on genome similarity between both causal viruses, followed by MERS and other human coronavirus diseases. Using our AutoSeed pipeline (text mining and database searches), we obtained 34 COVID-2019-related genes. Taking those genes as seeds, we automatically built a molecular network for which our module detection and drug prioritization algorithms identified 24 disease-related human pathways, five modules and finally suggested 78 drugs to repurpose. Following manual filtering based on clinical knowledge, we re-prioritized 30 potential repurposable drugs against COVID-2019 (including pseudoephedrine, andrographolide, chloroquine, abacavir, and thalidomide) . We hope that this data can provide critical insights into SARS-CoV-2 biology and help design rapid clinical trials of treatments against COVID-2019.

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Detecting and Profiling Endogenous RNA G-Quadruplexes in the Human Transcriptome

International Journal of Molecular Sciences ◽

10.3390/ijms22158012 ◽

2021 ◽

Vol 22 (15) ◽

pp. 8012

Author(s):

Rongxin Zhang ◽

Yajun Liu ◽

Xingxing Zhang ◽

Ke Xiao ◽

Yue Hou ◽

...

Keyword(s):

Bioinformatics Analysis ◽

Biological Functions ◽

Bioinformatics Pipeline ◽

The Real ◽

Human Transcriptome ◽

Gene Sets ◽

Nucleic Acid Structures ◽

Regulatory Functions ◽

Whole Transcriptome ◽

Insight Into

G-quadruplexes are the non-canonical nucleic acid structures that are preferentially formed in G-rich regions. This structure has been shown to be associated with many biological functions. Regardless of the broad efforts on DNA G-quadruplexes, we still have limited knowledge on RNA G-quadruplexes, especially in a transcriptome-wide manner. Herein, by integrating the DMS-seq and the bioinformatics pipeline, we profiled and depicted the RNA G-quadruplexes in the human transcriptome. The genes that contain RNA G-quadruplexes in their specific regions are significantly related to immune pathways and the COVID-19-related gene sets. Bioinformatics analysis reveals the potential regulatory functions of G-quadruplexes on miRNA targeting at the scale of the whole transcriptome. In addition, the G-quadruplexes are depleted in the putative, not the real, PAS-strong poly(A) sites, which may weaken the possibility of such sites being the real cleaved sites. In brief, our study provides insight into the potential function of RNA G-quadruplexes in post-transcription.

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Molecular Basis of the Leishmanicidal Activity of the Antidepressant Sertraline as a Drug Repurposing Candidate

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01928-18 ◽

2018 ◽

Vol 62 (12) ◽

Cited By ~ 8

Author(s):

Marta L. Lima ◽

María A. Abengózar ◽

Montserrat Nácher-Vázquez ◽

María P. Martínez-Alcázar ◽

Coral Barbas ◽

...

Keyword(s):

Visceral Leishmaniasis ◽

Drug Repurposing ◽

Content Type ◽

Intracellular Amino Acids ◽

Thiol Redox ◽

Clinical Drugs ◽

Metabolic Disarray ◽

Moderate Cost ◽

New Treatments ◽

Insight Into

ABSTRACTDrug repurposing affords the implementation of new treatments at a moderate cost and under a faster time-scale. Most of the clinical drugs againstLeishmaniashare this origin. The antidepressant sertraline has been successfully assayed in a murine model of visceral leishmaniasis. Nevertheless, sertraline targets inLeishmaniawere poorly defined. In order to get a detailed insight into the leishmanicidal mechanism of sertraline onLeishmania infantum, unbiased multiplatform metabolomics and transmission electron microscopy were combined with a focused insight into the sertraline effects on the bioenergetics metabolism of the parasite. Sertraline induced respiration uncoupling, a significant decrease of intracellular ATP level, and oxidative stress inL. infantumpromastigotes. Metabolomics evidenced an extended metabolic disarray caused by sertraline. This encompasses a remarkable variation of the levels of thiol-redox and polyamine biosynthetic intermediates, as well as a shortage of intracellular amino acids used as metabolic fuel byLeishmania. Sertraline killedLeishmaniathrough a multitarget mechanism of action, tackling essential metabolic pathways of the parasite. As such, sertraline is a valuable candidate for visceral leishmaniasis treatment under a drug repurposing strategy.

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Insight into the haem d 1 biosynthesis pathway in heliobacteria through bioinformatics analysis

Microbiology ◽

10.1099/mic.0.2007/007930-0 ◽

2007 ◽

Vol 153 (10) ◽

pp. 3548-3562 ◽

Cited By ~ 9

Author(s):

Jin Xiong ◽

Carl E. Bauer ◽

Anjly Pancholy

Keyword(s):

Bioinformatics Analysis ◽

Biosynthesis Pathway ◽

Insight Into

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Integrative transcriptome imputation reveals tissue-specific and shared biological mechanisms mediating susceptibility to complex traits

10.1101/532929 ◽

2019 ◽

Cited By ~ 1

Author(s):

Wen Zhang ◽

Georgios Voloudakis ◽

Veera M. Rajagopal ◽

Ben Reahead ◽

Joel T. Dudley ◽

...

Keyword(s):

Gene Expression ◽

Complex Traits ◽

Large Scale ◽

Association Studies ◽

Drug Repurposing ◽

Joint Analysis ◽

Expression Trait ◽

Significant Expression ◽

Insight Into ◽

Trait Associations

AbstractTranscriptome-wide association studies integrate gene expression data with common risk variation to identify gene-trait associations. By incorporating epigenome data to estimate the functional importance of genetic variation on gene expression, we improve the accuracy of transcriptome prediction and the power to detect significant expression-trait associations. Joint analysis of 14 large-scale transcriptome datasets and 58 traits identify 13,724 significant expression-trait associations that converge to biological processes and relevant phenotypes in human and mouse phenotype databases. We perform drug repurposing analysis and identify known and novel compounds that mimic or reverse trait-specific changes. We identify genes that exhibit agonistic pleiotropy for genetically correlated traits that converge on shared biological pathways and elucidate distinct processes in disease etiopathogenesis. Overall, this comprehensive analysis provides insight into the specificity and convergence of gene expression on susceptibility to complex traits.

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Novel IncR/IncP6 Hybrid Plasmid pCRE3-KPC Recovered from a Clinical KPC-2-Producing Citrobacter braakii Isolate

mSphere ◽

10.1128/msphere.00891-19 ◽

2020 ◽

Vol 5 (2) ◽

Author(s):

Dandan Dong ◽

Ziqiang Mi ◽

Dujun Li ◽

Mingming Gao ◽

Nan Jia ◽

...

Keyword(s):

Bioinformatics Analysis ◽

Multidrug Resistant ◽

Genomic Diversity ◽

Hybrid Plasmid ◽

The Novel ◽

Antimicrobial Susceptibility Test ◽

Genetic Characteristics ◽

Content Type ◽

Carbapenemase Gene ◽

Insight Into

ABSTRACT Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae have become widespread in hospitals and the environment. Here, we describe a blaKPC-2-carrying plasmid called pCRE3-KPC, which was recovered from a clinical multidrug-resistant Citrobacter braakii CRE3 strain in China. The complete nucleotide sequence of pCRE3-KPC was determined by combining MiSeq and MinION sequencing and then compared with those of three related plasmids. Plasmid conjugal transfer and electroporation tests, modified carbapenem inactivation method, and bacterial antimicrobial susceptibility test were carried out. We compared this plasmid with three related plasmids to verify that the backbone of pCRE3-KPC was composed of the backbones of the IncR plasmid and IncP6 plasmid. Further bioinformatics analysis showed that pCRE3-KPC carried two resistance-related regions (the blaKPC-2 gene cluster and the aacC2-tmrB-related region). The aacC2-tmrB-related region included two novel insertion sequences (ISCfr28 and ISCfr16). IMPORTANCE Reports of human-pathogenic C. braakii strains, especially of strains showing resistance to carbapenems, are rare. To the best of our knowledge, our results represent the first detection of carbapenemase gene blaKPC-2 in C. braakii strains. In addition, we have studied detailed genetic characteristics of the novel IncR/IncP6 hybrid plasmid pCRE3-KPC, which was isolated from a clinical multidrug-resistant Citrobacter braakii CRE3 strain. Our results may provide further insight into the horizontal transfer of multidrug resistance genes in bacteria and into the genomic diversity and molecular evolution of plasmids.

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Drug Repurposing for Hepatocellular Carcinoma via Virtual Screening Integrated with Bioinformatics Analysis

Special Publications - Conference on Drug Design and Discovery Technologies ◽

10.1039/9781839160783-00073 ◽

2019 ◽

pp. 73-78

Author(s):

Nair Gouri ◽

G. N. S. Hema Sree ◽

Rajalekshmi Saraswathy Ganesan ◽

K. Viswam Subeesh ◽

Anbu Jayaraman

Keyword(s):

Hepatocellular Carcinoma ◽

Virtual Screening ◽

Bioinformatics Analysis ◽

Drug Repurposing

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Artificial intelligence against COVID-19 Pandemic: A Comprehensive Insight

Current Medical Imaging Formerly Current Medical Imaging Reviews ◽

10.2174/1573405617666211004115208 ◽

2021 ◽

Vol 17 ◽

Author(s):

Azhar Equbal ◽

Sarfaraz Masood ◽

Iftekhar Equbal ◽

Shafi Ahmad ◽

Noor Zaman Khan ◽

...

Keyword(s):

Artificial Intelligence ◽

Modern Science ◽

Drug Repurposing ◽

Extensive Literature ◽

Imaging Data ◽

Trend Prediction ◽

Infective Disease ◽

Novel Coronavirus ◽

Insight Into

: COVID-19 is a pandemic initially identified in Wuhan, China, which is caused by a novel coronavirus, also recognized as the Severe Acute Respiratory Syndrome (SARS-nCoV-2). Unlike other coronaviruses, this novel pathogen may cause unusual contagious pain which results in viral pneumonia, serious heart problems, and even death. Researchers worldwide are continuously striving to develop a cure for this highly infective disease, yet there are no well-defined absolute treatments available at present. Several vaccination drives with emergency use authorisation vaccines are being done across many countries, however, their long term efficacy and side-effects study are yet to be done. The research community is analysing the situation by collecting the datasets from various sources. Healthcare professionals must thoroughly analyse the situation, devise preventive measures for this pandemic, and even develop possible drug combinations. Various analytical and statistical models have been developed, however, their outcome rate is prolonged. Thus, modern science stresses on the application of state-of-the-art methods in this combat against COVID-19. The application of Artificial intelligence (AI), and AI-driven tools are emerging as effective tools, especially with X-Ray and CT-Scan imaging data of infected subjects, infection trend predictions etc. The high efficacy of these AI systems can be observed in terms of highly accurate results, i.e. >95%, as reported in various studies. AI-driven tools are being used in COVID diagnostic, therapeutics, trend prediction, drug design and prevention to help fight against this pandemic. This paper aims to provide a deep insight into the comprehensive literature about AI and AI-driven tools in this battle against the COVID-19 pandemic. The extensive literature is divided into five sections, each describing the application of AI against COVID-19 viz. COVID-19 Prevention, diagnostic, infection spread trend prediction, therapeutic and drug repurposing.

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