Transcriptomics-based drug repositioning pipeline identifies therapeutic candidates for COVID-19
| العنوان: | Transcriptomics-based drug repositioning pipeline identifies therapeutic candidates for COVID-19 |
|---|---|
| المؤلفون: | Marina Sirota, Kris M. White, Romel Rosales, Brian L. Le, Gaia Andreoletti, Katharine Yu, Albert Vallejo-Gracia, Christine Li, G. Renuka Kumar, Adolfo García-Sastre, Daniel G. Bunis, Idit Kosti, Melanie Ott, Tomiko Oskotsky, Kristoffer E Leon |
| المصدر: | Scientific reports, vol 11, iss 1 Scientific Reports, Vol 11, Iss 1, Pp 1-14 (2021) Scientific Reports Research Square article-version (status) pre article-version (number) 1 |
| بيانات النشر: | eScholarship, University of California, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Drug, Coronavirus disease 2019 (COVID-19), media_common.quotation_subject, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Science, Computational biology, Biology, Antiviral Agents, Article, Clofazimine, Transcriptome, Vaccine Related, Biodefense, medicine, Humans, Lung, media_common, Multidisciplinary, Drug discovery, SARS-CoV-2, Prevention, Drug Repositioning, Computational Biology, COVID-19, Pneumonia, Human cell, Pipeline (software), Computational biology and bioinformatics, COVID-19 Drug Treatment, Drug repositioning, Emerging Infectious Diseases, Infectious Diseases, Good Health and Well Being, 5.1 Pharmaceuticals, Medicine, Development of treatments and therapeutic interventions, Infection, medicine.drug |
| الوصف: | 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 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). 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. |
| وصف الملف: | application/pdf |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b07339d7d9ccfa7485c892a597a75566Test https://escholarship.org/uc/item/44s17770Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b07339d7d9ccfa7485c892a597a75566 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |