Since the 2019 novel coronavirus disease (COVID-19) outbreak in 2019 and the pandemic continues for more than one year, a vast amount of drug research has been conducted and few of them got FDA approval. Our objective is to prioritize repurposable drugs using a pipeline that systematically integrates the interaction between COVID-19 and drugs, deep graph neural networks, and in vitro/population-based validations. We first collected all available drugs (n = 3635) related to COVID-19 patient treatment through CTDbase. We built a COVID-19 knowledge graph based on the interactions among virus baits, host genes, pathways, drugs, and phenotypes. A deep graph neural network approach was used to derive the candidate drug’s representation based on the biological interactions. We prioritized the candidate drugs using clinical trial history, and then validated them with their genetic profiles, in vitro experimental efficacy, and population-based treatment effect. We highlight the top 22 drugs including Azithromycin, Atorvastatin, Aspirin, Acetaminophen, and Albuterol. We further pinpointed drug combinations that may synergistically target COVID-19. In summary, we demonstrated that the integration of extensive interactions, deep neural networks, and multiple evidence can facilitate the rapid identification of candidate drugs for COVID-19 treatment.
【저자키워드】 Drug development, Virtual screening, 【초록키워드】 COVID-19, Treatment, 2019 novel coronavirus disease, coronavirus disease, Efficacy, clinical trial, pandemic, Azithromycin, Genetic, drugs, drug, drug combinations, in vitro, novel coronavirus disease, virus, Novel coronavirus, COVID-19 treatment, 2019 novel coronavirus, outbreak, Research, Knowledge graph, atorvastatin, Aspirin, disease, interactions, Evidence, Interaction, integration, Pathways, COVID-19 patient, acetaminophen, Phenotypes, COVID-19 knowledge, drug combination, profiles, FDA approval, albuterol, host genes, candidate drugs, approach, highlight, was used, collected, conducted, facilitate, demonstrated, candidate drug, 【제목키워드】 COVID-19, Drug repurposing, Evidence,