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Rapid Identification of Druggable Targets and the Power of the PHENotype SIMulator for Effective Drug Repurposing in COVID-19
The current, rapidly diversifying pandemic has accelerated the need for efficient and effective identification of potential drug candidates for COVID-19. Knowledge on host-immune response to SARS-CoV-2 infection, however, remains limited with very few drugs approved to date. Viable strategies and to...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Journal Experts
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057245/ https://www.ncbi.nlm.nih.gov/pubmed/33880466 http://dx.doi.org/10.21203/rs.3.rs-287183/v1 |
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author | Maria, Naomi I. Rapicavoli, Rosaria Valentina Alaimo, Salvatore Bischof, Evelyne Stasuzzo, Alessia Broek, Jantine A.C. Pulvirenti, Alfredo Mishra, Bud Duits, Ashley J. Ferro, Alfredo |
author_facet | Maria, Naomi I. Rapicavoli, Rosaria Valentina Alaimo, Salvatore Bischof, Evelyne Stasuzzo, Alessia Broek, Jantine A.C. Pulvirenti, Alfredo Mishra, Bud Duits, Ashley J. Ferro, Alfredo |
author_sort | Maria, Naomi I. |
collection | PubMed |
description | The current, rapidly diversifying pandemic has accelerated the need for efficient and effective identification of potential drug candidates for COVID-19. Knowledge on host-immune response to SARS-CoV-2 infection, however, remains limited with very few drugs approved to date. Viable strategies and tools are rapidly arising to address this, especially with repurposing of existing drugs offering significant promise. Here we introduce a systems biology tool, the PHENotype SIMulator, which – by leveraging available transcriptomic and proteomic databases – allows modeling of SARS-CoV-2 infection in host cells in silico to i) determine with high sensitivity and specificity (both>96%) the viral effects on cellular host-immune response, resulting in a specific cellular SARS-CoV-2 signature and ii) utilize this specific signature to narrow down promising repurposable therapeutic strategies. Powered by this tool, coupled with domain expertise, we have identified several potential COVID-19 drugs including methylprednisolone and metformin, and further discern key cellular SARS-CoV-2-affected pathways as potential new drugable targets in COVID-19 pathogenesis. |
format | Online Article Text |
id | pubmed-8057245 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Journal Experts |
record_format | MEDLINE/PubMed |
spelling | pubmed-80572452021-04-21 Rapid Identification of Druggable Targets and the Power of the PHENotype SIMulator for Effective Drug Repurposing in COVID-19 Maria, Naomi I. Rapicavoli, Rosaria Valentina Alaimo, Salvatore Bischof, Evelyne Stasuzzo, Alessia Broek, Jantine A.C. Pulvirenti, Alfredo Mishra, Bud Duits, Ashley J. Ferro, Alfredo Res Sq Article The current, rapidly diversifying pandemic has accelerated the need for efficient and effective identification of potential drug candidates for COVID-19. Knowledge on host-immune response to SARS-CoV-2 infection, however, remains limited with very few drugs approved to date. Viable strategies and tools are rapidly arising to address this, especially with repurposing of existing drugs offering significant promise. Here we introduce a systems biology tool, the PHENotype SIMulator, which – by leveraging available transcriptomic and proteomic databases – allows modeling of SARS-CoV-2 infection in host cells in silico to i) determine with high sensitivity and specificity (both>96%) the viral effects on cellular host-immune response, resulting in a specific cellular SARS-CoV-2 signature and ii) utilize this specific signature to narrow down promising repurposable therapeutic strategies. Powered by this tool, coupled with domain expertise, we have identified several potential COVID-19 drugs including methylprednisolone and metformin, and further discern key cellular SARS-CoV-2-affected pathways as potential new drugable targets in COVID-19 pathogenesis. American Journal Experts 2021-04-14 /pmc/articles/PMC8057245/ /pubmed/33880466 http://dx.doi.org/10.21203/rs.3.rs-287183/v1 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. |
spellingShingle | Article Maria, Naomi I. Rapicavoli, Rosaria Valentina Alaimo, Salvatore Bischof, Evelyne Stasuzzo, Alessia Broek, Jantine A.C. Pulvirenti, Alfredo Mishra, Bud Duits, Ashley J. Ferro, Alfredo Rapid Identification of Druggable Targets and the Power of the PHENotype SIMulator for Effective Drug Repurposing in COVID-19 |
title | Rapid Identification of Druggable Targets and the Power of the PHENotype SIMulator for Effective Drug Repurposing in COVID-19 |
title_full | Rapid Identification of Druggable Targets and the Power of the PHENotype SIMulator for Effective Drug Repurposing in COVID-19 |
title_fullStr | Rapid Identification of Druggable Targets and the Power of the PHENotype SIMulator for Effective Drug Repurposing in COVID-19 |
title_full_unstemmed | Rapid Identification of Druggable Targets and the Power of the PHENotype SIMulator for Effective Drug Repurposing in COVID-19 |
title_short | Rapid Identification of Druggable Targets and the Power of the PHENotype SIMulator for Effective Drug Repurposing in COVID-19 |
title_sort | rapid identification of druggable targets and the power of the phenotype simulator for effective drug repurposing in covid-19 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057245/ https://www.ncbi.nlm.nih.gov/pubmed/33880466 http://dx.doi.org/10.21203/rs.3.rs-287183/v1 |
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