Novel Development of Predictive Feature Fingerprints to Identify Chemistry-Based Features for the Effective Drug Design of SARS-CoV-2 Target Antagonists and Inhibitors Using Machine Learning

利用机器学习开发预测特征指纹图谱,以识别基于化学的特征,从而有效设计SARS-CoV-2靶点拮抗剂和抑制剂

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Abstract

A unique approach to bioactivity and chemical data curation coupled with random forest analyses has led to a series of target-specific and cross-validated predictive feature fingerprints (PFF) that have high predictability across multiple therapeutic targets and disease stages involved in the severe acute respiratory syndrome due to coronavirus 2 (SARS-CoV-2)-induced COVID-19 pandemic, which include plasma kallikrein, human immunodeficiency virus (HIV)-protease, nonstructural protein (NSP)5, NSP12, Janus kinase (JAK) family, and AT-1. The approach was highly accurate in determining the matched target for the different compound sets and suggests that the models could be used for virtual screening of target-specific compound libraries. The curation-modeling process was successfully applied to a SARS-CoV-2 phenotypic screen and could be used for predictive bioactivity estimation and prioritization for clinical trial selection; virtual screening of drug libraries for the repurposing of drug molecules; and analysis and direction of proprietary data sets.

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