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SARS-CoV-2 proteins

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    Transcriptomics-based drug repositioning pipeline identifies therapeutic candidates for COVID-19 MESHD

    Authors: Brian L Le; Gaia Andreoletti; Tomiko Oskotsky; Albert Vallejo-Gracia; Romel Rosales; Katharine Z Yu; Idit Kosti; Kristoffer E Leon; Daniel G Bunis; Christine Li; G. Renuka Kumar; Kris M. White; Adolfo E García-Sastre; Melanie Ott; Marina Sirota; Marcelo Yanovsky; Andrea Gamarnik; Bart N Lambrecht; Lynda Coughlan; Adolfo Garcia-Sastre; Bruno G De Geest; Michael Schotsaert; Marion Yger; Bertrand Degos; Louise-Laure Mariani; Christophe Bouche; Nathalie Dzierzynski; Bruno Oquendo; Flora Ketz; An-Hung Nguyen; Aurelie Kas; Jean-Yves Delattre; Jean-Christophe Corvol

    doi:10.1101/2020.10.23.352666 Date: 2020-10-23 Source: bioRxiv

    The novel SARS-CoV-2 virus emerged in December 2019 and has few effective treatments. We applied a computational drug repositioning pipeline to SARS-CoV-2 differential gene expression signatures derived from publicly available data. We utilized three independent published studies to acquire or generate lists of differentially expressed genes between control and SARS-CoV-2-infected MESHD samples. Using a rank-based pattern matching strategy based on the Kolmogorov-Smirnov Statistic, the signatures were queried against drug profiles from Connectivity Map ( CMap HGNC). We validated sixteen of our top predicted hits in live SARS-CoV-2 antiviral assays in either Calu-3 or 293T-ACE2 cells. Validation experiments in human cell lines showed that 11 of the 16 compounds tested to date (including clofazimine, haloperidol and others) had measurable antiviral activity against SARS-CoV-2. These initial results are encouraging as we continue to work towards a further analysis of these predicted drugs as potential therapeutics for the treatment of COVID-19 MESHD.

    In silico Drug Repurposing to combat COVID-19 MESHD based on Pharmacogenomics of Patient Transcriptomic Data

    Authors: Shaoli Das; Kevin Camphausen; Uma Shankavaram

    doi:10.21203/rs.3.rs-39128/v1 Date: 2020-06-29 Source: ResearchSquare

    The ongoing global pandemic of coronavirus disease 2019 MESHD ( COVID-19 MESHD) continues to affect a growing number of populations in different parts of the world. In the current situation, drug repurposing is a viable strategy to combat COVID-19 MESHD. The drugs targeting the host receptors that interact with SARS-CoV-2 are possible candidates. However, assessment of their effectiveness in COVID-19 MESHD patients is necessary before prioritizing them for further study. We attempted to shortlist the candidate drugs using an in-silico approach. First, we analysed two published transcriptomic data sets of COVID-19 MESHD- and SARS-infected MESHD patients compared to healthy individuals to find the key pathways altered after infection. Then, using publicly available drug perturbational data sets in human cell lines from the Broad Institute Connectivity Map ( CMAP HGNC), we assessed the effects of the approved drugs on the altered pathways. We also used the available pharmacogenomic data sets from the Genomics of Drug Sensitivity in Cancer MESHD (GDSC) portal to assess the effects of the altered pathways on resistance or sensitivity to the drugs in human cell lines. Our analysis identified many candidate drugs, some of which are already being investigated for treatment of COVID-19 MESHD and can serve as a basis for prioritizing additional viable candidate drugs for COVID-19 MESHD.

    A Connectivity Map-Based Drug Repurposing Study and Integrative Analysis of Transcriptomic Profiling of SARS-CoV-2 Infection MESHD

    Authors: seyedeh zahra mousavi; mojdeh rahmanian; ashkan sami

    doi:10.26434/chemrxiv.12469316.v1 Date: 2020-06-15 Source: ChemRxiv

    Aims: The recent outbreak of COVID-19 MESHD 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 MESHD 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 MESHD cell lines including “the primary human lung epithelial cell line NHBE” and “the transformed lung alveolar MESHD cell line A549”. Next, the identified DEGs are used in the connectivity map ( CMap HGNC) 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 overrepresentations of each pathway are tested in comparison to what is expected randomly.Key findings: The results suggest the effectiveness of Saquinavir, lansoprazole, folic acid, ebselen, aminocaproic acid, simvastatin, surfactant stimulant drugs, heat shock protein 90 ( HSP90 HGNC) inhibitors, histone deacetylase (HDAC) inhibitors, metronidazole, inhaled corticosteroids (ICS) and many other clinically approved drugs and investigational compounds as potent drugs against COVID-19 MESHD outbreak.Significance: 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 HGNC analysis has been investigated according to previous research.

    Discovery of potential drugs for COVID-19 MESHD based on the connectivity map

    Authors: Zhonglin Li; Tao Bai; Ling Yang; Xiaohua Hou

    doi:10.21203/rs.2.24684/v1 Date: 2020-02-25 Source: ResearchSquare

    Background: Corona virus infective disease MESHD 19 ( COVID-19 MESHD) is the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and spreads very rapidly, which become a worldwide public healthy crisis. Until now, there is no effective antivirus drugs or vaccines specifically used for its treatment. So it is urgent to discover efficient therapeutic methods. The same as SARS-CoV, SARS-CoV-2 MESHD also invades organism by combining with Angiotensin-converting enzyme 2 HGNC ( ACE2 HGNC). Recently, there are reports about SARS-CoV-2 infected MESHD host not only through the respiratory tract, but also gastrointestinal tract. However, it is proved that ACE2 HGNC plays a key role in protecting subjects from lung injury MESHD and resisting the inflammation MESHD caused by intestinal epithelial damage. Interestingly, the expression of ACE2 HGNC protein is reduced after SARS-CoV infection MESHD. Methods: According to the dataset of genes co-expressed with ACE2 HGNC in the colonic epithelial cells, we established a protein-protein interaction (PPI) Network and selected hub genes from them. The cluster analysis was performed to find out the dense region of the PPI Network. Then, gene ontology (GO) and pathway enrichment analysis were performed to explore the main function of genes co-expressed with ACE2 HGNC. Finally, we predicted the potential drugs for the treatment of COVID-19 MESHD based on the connectivity map ( Cmap HGNC) . Results: We constructed a PPI network containing 125 hub genes of genes co-expressed with ACE2 HGNC in the colonic epithelial cells and obtained two modules through cluster analysis. The GO analysis and the KEGG pathway revealed these genes were aggregated in ribosome, exosomes, extracellular cellular components; structure constituent of ribosome, G-protein coupled receptor activity, MHC class I and II receptor activity biological processes; immune response, protein metabolism, signal transduction biological processes; and ribosome, graft-versus-host disease MESHD, viral myocarditis MESHD pathways. The result from Cmap HGNC indicated ikarugamycin, molsidomine had highly correlated scores with the query files. Conclusion: We found out that ikarugamycin and molsidomine were the potential drugs for the treatment of COVID-19 MESHD.

The ZB MED preprint Viewer preVIEW includes all COVID-19 related preprints from medRxiv and bioRxiv, from ChemRxiv, from ResearchSquare, from arXiv and from Preprints.org and is updated on a daily basis (7am CET/CEST).
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MeSH Disease
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SARS-CoV-2 Proteins


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