Transcriptome-based drug repositioning for coronavirus disease 2019 (COVID-19)

• Published in: Pathogens and Disease Vol. 78; no. 4
• Main Authors: Jia, Zhilong, Song, Xinyu, Shi, Jinlong, Wang, Weidong, He, Kunlun
• Format: Journal Article Web Resource
• Language: English
• Published: United States Oxford University Press 01.06.2020
• Subjects: Antiviral agents; Antiviral Agents - pharmacology; Betacoronavirus - drug effects; Bronchoalveolar Lavage Fluid - chemistry; Bronchus; Cell Degranulation - immunology; Coronavirus Infections - drug therapy; Coronaviruses; COVID-19; Degranulation; Dexamethasone; Disease; Drug development; Drug Repositioning; Drugs; Endocytosis; Endocytosis - immunology; Gene Expression Profiling; Gene regulation; Health services; Humans; Infectious diseases; Lavage; Leukocytes (neutrophilic); Lysosomes - immunology; Molecular docking; Molecular Docking Simulation; Morbidity; Neutrophil Activation - immunology; Pandemics; Pneumonia; Pneumonia, Viral - drug therapy; Public health; Respiratory diseases; Ribavirin; Ribavirin - pharmacology; Saquinavir; Saquinavir - pharmacology; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Transcriptome; Transcriptomes; Viral diseases; COVID-19; saquinavir, ribavirin; SARS-CoV-2; drug repositioning; neutrophil degranulation
• ISSN: 2049-632X; 2049-632X
• DOI: 10.1093/femspd/ftaa036

ABSTRACT The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) around the world has led to a pandemic with high morbidity and mortality. However, there are no effective drugs to prevent and treat the disease. Transcriptome-based drug repositioning, identifying new indications for old drugs, is a powerful tool for drug development. Using bronchoalveolar lavage fluid transcriptome data of COVID-19 patients, we found that the endocytosis and lysosome pathways are highly involved in the disease and that the regulation of genes involved in neutrophil degranulation was disrupted, suggesting an intense battle between SARS-CoV-2 and humans. Furthermore, we implemented a coexpression drug repositioning analysis, cogena, and identified two antiviral drugs (saquinavir and ribavirin) and several other candidate drugs (such as dinoprost, dipivefrine, dexamethasone and (-)-isoprenaline). Notably, the two antiviral drugs have also previously been identified using molecular docking methods, and ribavirin is a recommended drug in the diagnosis and treatment protocol for COVID pneumonia (trial version 5–7) published by the National Health Commission of the P.R. of China. Our study demonstrates the value of the cogena-based drug repositioning method for emerging infectious diseases, improves our understanding of SARS-CoV-2-induced disease, and provides potential drugs for the prevention and treatment of COVID-19 pneumonia. Transcriptome-based drug repositioning for COVID-19 recovered two antiviral drugs and identified several candidate drugs, including saquinavir, ribavirin, dinoprost and dexamethasone.