This study describes complementary network-based and sequence similarity methods to identify drug repurposing opportunities predicted to directly target viral proteins, highlighting results for five human pathogens. This study describes two complementary methods that use network-based and sequence similarity tools to identify drug repurposing opportunities predicted to modulate viral proteins. This approach could be rapidly adapted to new and emerging viruses. The first method built and studied a virus–host–physical interaction network; a three-layer multimodal network of drug target proteins, human protein–protein interactions, and viral–host protein–protein interactions. The second method evaluated sequence similarity between viral proteins and other proteins, visualized by constructing a virus–host–similarity interaction network. Methods were validated on the human immunodeficiency virus, hepatitis B, hepatitis C, and human papillomavirus, then deployed on SARS-CoV-2. Comparison of virus–host–physical interaction predictions to known antiviral drugs had AUCs of 0.69, 0.59, 0.78, and 0.67, respectively, reflecting that the scores are predictive of effective drugs. For SARS-CoV-2, 569 candidate drugs were predicted, of which 37 had been included in clinical trials for SARS-CoV-2 (AUC = 0.75, P -value 3.21 × 10 −3 ). As further validation, top-ranked candidate antiviral drugs were analyzed for binding to protein targets in silico; binding scores generated by BindScope indicated a 70% success rate.
【초록키워드】 viruses, SARS-CoV-2, clinical trial, antiviral drugs, clinical trials, Viral proteins, Proteins, antiviral drug, effective drugs, Viral, Hepatitis, hepatitis C, drug target, hepatitis B, Pathogens, Human immunodeficiency virus, binding, Interaction, protein–protein interactions, AUC, complementary, Predictive, human papillomavirus, Viral protein, immunodeficiency virus, P -value, sequence similarity, protein interactions, protein targets, papillomavirus, binding scores, approach, FIVE, Protein target, predicted, analyzed, identify, indicated, evaluated, modulate, highlighting, binding score, candidate drug, 【제목키워드】 SARS-CoV-2, Antiviral,