Abstract
Currently, coronavirus disease 2019 (COVID-19), has posed an imminent threat to global public health. Although some current therapeutic agents have showed potential prevention or treatment, a growing number of associated adverse events have occurred on patients with COVID-19 in the course of medical treatment. Therefore, a comprehensive assessment of the safety profile of therapeutic agents against COVID-19 is urgently needed. In this study, we proposed a network-based framework to identify the potential side effects of current COVID-19 drugs in clinical trials. We established the associations between 116 COVID-19 drugs and 30 kinds of human tissues based on network proximity and gene-set enrichment analysis (GSEA) approaches. Additionally, we focused on four types of drug-induced toxicities targeting four tissues, including hepatotoxicity, renal toxicity, lung toxicity, and neurotoxicity, and validated our network-based predictions by preclinical and clinical evidence available. Finally, we further performed pharmacovigilance analysis to validate several drug-tissue toxicities via data mining adverse event reporting data, and we identified several new drug-induced side effects without labeling in Food and Drug Administration (FDA) drug instructions. Overall, this study provides forceful approaches to assess potential side effects on COVID-19 drugs, which will be helpful for their safe use in clinical practice and promoting the discovery of antiviral therapeutics against SARS-CoV-2.
【저자키워드】 pharmacovigilance, Network proximity, Side effect, COVID-19 drug, CMap, OpenVigil, 【초록키워드】 COVID-19, Treatment, coronavirus disease, SARS-CoV-2, drugs, lung, clinical trials, Toxicity, drug, FDA, adverse event, therapeutic agent, antiviral therapeutics, safety profile, Clinical practice, association, food, Analysis, Safe, tissues, global public health, approaches, clinical evidence, renal, GSEA, labeling, approach, Course, identify, performed, occurred, human tissue, provide, gene-set enrichment analysis, patients with COVID-19, 【제목키워드】 COVID-19, Perspective, Comprehensive,