Phenotype-driven identification of drug targets for post-COVID-19 anosmia

Abstract

AbstractAnosmia (loss of sense of smell) is one symptom of COVID-19 which can linger long after acute infection has passed, with major impact on quality of life. Given the number of people impacted by COVID-19-related anosmia, there is an urgent need to identify effective therapeutics in a faster fashion than using traditional drug discovery and development methods. We used our knowledge graph, the Phenograph, to navigate from phenotypes to genes to drug targets, to rapidly find druggable targets associated with anosmia. This process shortlisted six targets: NRP1, SCN9A, EGR1, VEGFB, PRKCE, and FGFR1. Neuropilin-1 (NRP1) is under active study for its involvement in SARS-CoV-2 infection. Importantly, there is no direct link between anosmia and NRP1 in our knowledge graph; the relationship was inferred through the graph structure. Based on this external validation, we derived hypotheses for the involvement of the remaining five targets in COVID-19-related anosmia, and the mechanism of action desired in a drug candidate to correct the hypothesized dysregulation.