Priority index for critical Covid-19 identifies clinically actionable targets and drugs.
Zhang Z., Wang S., Jiang L., Wei J., Lu C., Li S., Diao Y., Fang Z., He S., Tan T., Yang Y., Zou K., Shi J., Lin J., Chen L., Bao C., Fei J., Fang H.
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.