Priority index for critical Covid-19 identifies clinically actionable targets and drugs
© 2024. The Author(s)..
While genome-wide studies have identified genomic loci in hosts associated with life-threatening Covid-19 (critical Covid-19), the challenge of resolving these loci hinders further identification of clinically actionable targets and drugs. Building upon our previous success, we here present a priority index solution designed to address this challenge, generating the target and drug resource that consists of two indexes: the target index and the drug index. The primary purpose of the target index is to identify clinically actionable targets by prioritising genes associated with Covid-19. We illustrate the validity of the target index by demonstrating its ability to identify pre-existing Covid-19 phase-III drug targets, with the majority of these targets being found at the leading prioritisation (leading targets). These leading targets have their evolutionary origins in Amniota ('four-leg vertebrates') and are predominantly involved in cytokine-cytokine receptor interactions and JAK-STAT signaling. The drug index highlights opportunities for repurposing clinically approved JAK-STAT inhibitors, either individually or in combination. This proposed strategic focus on the JAK-STAT pathway is supported by the active pursuit of therapeutic agents targeting this pathway in ongoing phase-II/III clinical trials for Covid-19.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:7 |
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| Enthalten in: |
Communications biology - 7(2024), 1 vom: 16. Feb., Seite 189 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, Zhiqiang [VerfasserIn] |
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| Links: |
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| Themen: |
Cytokines |
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| Anmerkungen: |
Date Completed 19.02.2024 Date Revised 19.02.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s42003-024-05897-0 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM368561747 |
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| 520 | |a While genome-wide studies have identified genomic loci in hosts associated with life-threatening Covid-19 (critical Covid-19), the challenge of resolving these loci hinders further identification of clinically actionable targets and drugs. Building upon our previous success, we here present a priority index solution designed to address this challenge, generating the target and drug resource that consists of two indexes: the target index and the drug index. The primary purpose of the target index is to identify clinically actionable targets by prioritising genes associated with Covid-19. We illustrate the validity of the target index by demonstrating its ability to identify pre-existing Covid-19 phase-III drug targets, with the majority of these targets being found at the leading prioritisation (leading targets). These leading targets have their evolutionary origins in Amniota ('four-leg vertebrates') and are predominantly involved in cytokine-cytokine receptor interactions and JAK-STAT signaling. The drug index highlights opportunities for repurposing clinically approved JAK-STAT inhibitors, either individually or in combination. This proposed strategic focus on the JAK-STAT pathway is supported by the active pursuit of therapeutic agents targeting this pathway in ongoing phase-II/III clinical trials for Covid-19 | ||
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| 700 | 1 | |a Jiang, Lulu |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Jianwen |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Chang |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Shengli |e verfasserin |4 aut | |
| 700 | 1 | |a Diao, Yizhu |e verfasserin |4 aut | |
| 700 | 1 | |a Fang, Zhongcheng |e verfasserin |4 aut | |
| 700 | 1 | |a He, Shuo |e verfasserin |4 aut | |
| 700 | 1 | |a Tan, Tingting |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Yisheng |e verfasserin |4 aut | |
| 700 | 1 | |a Zou, Kexin |e verfasserin |4 aut | |
| 700 | 1 | |a Shi, Jiantao |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, James |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Liye |e verfasserin |4 aut | |
| 700 | 1 | |a Bao, Chaohui |e verfasserin |4 aut | |
| 700 | 1 | |a Fei, Jian |e verfasserin |4 aut | |
| 700 | 1 | |a Fang, Hai |e verfasserin |4 aut | |
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