Identification of potentially anti-COVID-19 active drugs using the connectivity MAP
Drug repurposing can be an interesting strategy for an emergency response to the severe acute respiratory syndrome-coronavirus-2, (SARS-COV-2), the causing agent of the coronavirus disease-19 (COVID-19) pandemic. For this, we applied the Connectivity Map (CMap) bioinformatic resource to identify drugs that generate, in the CMap database, gene expression profiles (GEP) that negatively correlate with a SARS-COV-2 GEP, anticipating that these drugs could antagonize the deleterious effects of the virus at cell, tissue or organism levels. We identified several anti-cancer compounds that target MDM2 in the p53 pathway or signaling proteins: Ras, PKBβ, Nitric Oxide synthase, Rho kinase, all involved in the transmission of proliferative and growth signals. We hypothesized that these drugs could interfere with the high rate of biomass synthesis in infected cells, a feature shared with cancer cells. Other compounds including etomoxir, triacsin-c, PTB1-IN-3, are known to modulate lipid metabolism or to favor catabolic reactions by activating AMPK. Four different anti-inflammatory molecules, including dexamethasone, fluorometholone and cytosporone-b, targeting the glucocorticoid receptor, cyclooxygenase, or NUR77 also came out of the analysis. These results represent a first step in the characterization of potential repositioning strategies to treat SARS-COV-2.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:17 |
|---|---|
| Enthalten in: |
PloS one - 17(2022), 1 vom: 28., Seite e0262751 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Bonnet, Raphaël [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Anti-Inflammatory Agents |
|---|
| Anmerkungen: |
Date Completed 03.02.2022 Date Revised 07.12.2022 published: Electronic-eCollection Citation Status MEDLINE |
|---|
| doi: |
10.1371/journal.pone.0262751 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM336196911 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM336196911 | ||
| 003 | DE-627 | ||
| 005 | 20231225231606.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1371/journal.pone.0262751 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1120.xml |
| 035 | |a (DE-627)NLM336196911 | ||
| 035 | |a (NLM)35085325 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Bonnet, Raphaël |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Identification of potentially anti-COVID-19 active drugs using the connectivity MAP |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 03.02.2022 | ||
| 500 | |a Date Revised 07.12.2022 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Drug repurposing can be an interesting strategy for an emergency response to the severe acute respiratory syndrome-coronavirus-2, (SARS-COV-2), the causing agent of the coronavirus disease-19 (COVID-19) pandemic. For this, we applied the Connectivity Map (CMap) bioinformatic resource to identify drugs that generate, in the CMap database, gene expression profiles (GEP) that negatively correlate with a SARS-COV-2 GEP, anticipating that these drugs could antagonize the deleterious effects of the virus at cell, tissue or organism levels. We identified several anti-cancer compounds that target MDM2 in the p53 pathway or signaling proteins: Ras, PKBβ, Nitric Oxide synthase, Rho kinase, all involved in the transmission of proliferative and growth signals. We hypothesized that these drugs could interfere with the high rate of biomass synthesis in infected cells, a feature shared with cancer cells. Other compounds including etomoxir, triacsin-c, PTB1-IN-3, are known to modulate lipid metabolism or to favor catabolic reactions by activating AMPK. Four different anti-inflammatory molecules, including dexamethasone, fluorometholone and cytosporone-b, targeting the glucocorticoid receptor, cyclooxygenase, or NUR77 also came out of the analysis. These results represent a first step in the characterization of potential repositioning strategies to treat SARS-COV-2 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Anti-Inflammatory Agents |2 NLM | |
| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 650 | 7 | |a Antiviral Agents |2 NLM | |
| 650 | 7 | |a Pharmaceutical Preparations |2 NLM | |
| 700 | 1 | |a Mariault, Lee |e verfasserin |4 aut | |
| 700 | 1 | |a Peyron, Jean-François |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t PloS one |d 2006 |g 17(2022), 1 vom: 28., Seite e0262751 |w (DE-627)NLM167327399 |x 1932-6203 |7 nnns |
| 773 | 1 | 8 | |g volume:17 |g year:2022 |g number:1 |g day:28 |g pages:e0262751 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1371/journal.pone.0262751 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 17 |j 2022 |e 1 |b 28 |h e0262751 | ||