LY294002 for COVID-19

Inositol plays many important roles in cellular processes through its various derivatives including phosphatidylinositol phosphates. Viruses use phosphatidylinositol phosphates for their replication in multiple processes including entry, formation of replication organelles, assembly and release. For these processes, viruses recruit phosphatidylinositol kinases to meet their demand of phosphatidylinositol phosphates. Inhibitors of phosphatidylinositol kinases have been shown to inhibit various viruses. The complexity of various types and isoforms of phosphatidylinositol kinases can be a problem in developing a broad-spectrum antiviral as different viruses use various types and isoforms of the enzyme. Inositol monophosphatase is an enzyme required for both de novo biosynthesis and intracellular recycling of inositol. It can provide a chokepoint to limit the availability of cellular inositol, phosphatidylinositol, and phosphatidylinositol phosphates. It can be a promising target for broad-spectrum antiviral development.

IntroductionThe COVID-19 Disease Map project is a large-scale community effort uniting 277 scientists from 130 Institutions around the globe. We use high-quality, mechanistic content describing SARS-CoV-2-host interactions and develop interoperable bioinformatic pipelines for novel target identification and drug repurposing. MethodsExtensive community work allowed an impressive step forward in building interfaces between Systems Biology tools and platforms. Our framework can link biomolecules from omics data analysis and computational modelling to dysregulated pathways in a cell-, tissue- or patient-specific manner. Drug repurposing using text mining and AI-assisted analysis identified potential drugs, chemicals and microRNAs that could target the identified key factors.ResultsResults revealed drugs already tested for anti-COVID-19 efficacy, providing a mechanistic context for their mode of action, and drugs already in clinical trials for treating other diseases, never tested against COVID-19. DiscussionThe key advance is that the proposed framework is versatile and expandable, offering a significant upgrade in the arsenal for virus-host interactions and other complex pathologies.