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      A connectivity map-based drug repurposing study and integrative analysis of transcriptomic profiling of SARS-CoV-2 infection


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          The recent outbreak of COVID-19 has become a global health concern. There are currently no effective treatment strategies and vaccines for the treatment or prevention of this fatal disease. The current study aims to determine promising treatment options for the COVID-19 through a computational drug repurposing approach.

          Materials and methods

          In this study, we focus on differentially expressed genes (DEGs), detected in SARS-CoV-2 infected cell lines including “the primary human lung epithelial cell line NHBE” and “the transformed lung alveolar cell line A549”. Next, the identified DEGs are used in the connectivity map (CMap) analysis to identify similarly acting therapeutic candidates. Furthermore, to interpret lists of DEGs, pathway enrichment and protein network analysis are performed. Genes are categorized into easily interpretable pathways based on their biological functions, and overrepresentation of each pathway is tested in comparison to what is expected randomly.

          Key findings

          The results suggest the effectiveness of lansoprazole, folic acid, sulfamonomethoxine, tolnaftate, diclofenamide, halcinonide, saquinavir, metronidazole, ebselen, lidocaine and benzocaine, histone deacetylase (HDAC) inhibitors, heat shock protein 90 (HSP90) inhibitors, and many other clinically approved drugs as potent drugs against COVID-19 outbreak.


          Making new drugs remain a lengthy process, so the drug repurposing approach provides an insight into the therapeutics that might be helpful in this pandemic. In this study, pathway enrichment and protein network analysis are also performed, and the effectiveness of some drugs obtained from the CMap analysis has been investigated according to previous researches.


          • Computational genomics analysis can accelerate drug discovery for the COVID-19.

          • SARS-CoV-2 transcriptome showed a chemokine-dominant hyperinflammatory response.

          • Robust IFN response with significant expression of ISGs pathway is seen in COVID-19.

          • The drug repurposing can be used as an alternative to de novo drug development.

          • Many approved drugs and investigational compounds showed antiviral properties.

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          Most cited references90

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          Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing

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            Is Open Access

            Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2

            In comparative high-throughput sequencing assays, a fundamental task is the analysis of count data, such as read counts per gene in RNA-seq, for evidence of systematic changes across experimental conditions. Small replicate numbers, discreteness, large dynamic range and the presence of outliers require a suitable statistical approach. We present DESeq2, a method for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates. This enables a more quantitative analysis focused on the strength rather than the mere presence of differential expression. The DESeq2 package is available at http://www.bioconductor.org/packages/release/bioc/html/DESeq2.html. Electronic supplementary material The online version of this article (doi:10.1186/s13059-014-0550-8) contains supplementary material, which is available to authorized users.
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              Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China

              Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and has subsequently spread worldwide. Risk factors for the clinical outcomes of COVID-19 pneumonia have not yet been well delineated.

                Author and article information

                Infect Genet Evol
                Infect Genet Evol
                Infection, Genetics and Evolution
                Elsevier B.V.
                29 October 2020
                29 October 2020
                : 104610
                [a ]Shiraz University of Medical Sciences, Shiraz, Iran
                [b ]Jahrom University, Jahrom, Iran
                [c ]Shiraz University, Shiraz, Iran
                Author notes
                [* ]Corresponding author at: Department of Computer Science and Engineering and IT, Shiraz University, Shiraz, Iran.
                S1567-1348(20)30441-X 104610
                © 2020 Elsevier B.V. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                : 13 June 2020
                : 29 September 2020
                : 23 October 2020
                Research Paper

                covid-19,sars-cov-2,drug repurposing,connectivity map,transcriptomic profiling
                covid-19, sars-cov-2, drug repurposing, connectivity map, transcriptomic profiling


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