Priority index for critical Covid-19 identifies clinically actionable targets and drugs

Journal article

Abstract 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

Authors: Zhang, Z; Wang, S; Jiang, L; Wei, J; Lu, C

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Nature Research
• Journal: Communications Biology
• Volume: 7
• Issue: 1
• Pages: 189-189
• Article number: 189
• Publication date: 2024-02-16
• DOI: 10.1038/s42003-024-05897-0
• EISSN: 2399-3642
• ISSN: 2399-3642
• Language: English
• Keywords: Gene; Computer science; Medicine; Repurposing; Drug repositioning; Therapeutic index; Coronavirus disease 2019 (COVID-19); Disease; Index (typography); Computational biology; Bioinformatics; Internal medicine; JAK-STAT signaling pathway; stat; Pharmacology; Receptor; Genetics; Drug target; Drug; Biology