The large-scale disruption caused by the COVID-19 pandemic has motivated researchers in academic, commercial and government sectors around the world to develop anti-SARS-CoV-2 therapeutics and vaccines. Drug repurposing has become an important approach to accelerate these efforts. By combining CAS REGISTRY, the world’s most authoritative collection of chemical information curated by hundreds of CAS information scientists, with data available from external databases, we developed a knowledge graph to support global research of drug repurposing for COVID-19. We identified 20 biological processes important for COVID-19 pathogenesis and utilized published data on host gene expression changes in response to SARS-CoV-2 infection to identify 16 more processes upregulated post-infection. These processes were then used as the starting point of a knowledge graph query to identify small molecules that target relevant genes. Our approach identified 1,350 potentially repurposeable drugs. We next developed a small molecule ranking method focused on rarity of the genes and biological processes within the graph to emphasize novel drug candidates. Among the top 50 small molecules identified by our algorithm, the two most common drug classes were kinase inhibitors and histone deacetylase inhibitors. Of the top 50 small molecules, 11 have been tested in COVID-19 clinical trials listed on clinicaltrial.gov. The high number of clinically tested drugs in our results suggests that the other 39 drug candidates should be investigated as potential therapeutics as well. We believe that our knowledge graph provides researchers an opportunity to accelerate innovation and streamline the investigative process not just for the COVID-19 pandemic but also in other biomedical and scientific research.

Knowledge graph-based approaches to drug repurposing for COVID-19

ACS Fall 2021

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