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抗登革热:一种基于机器学习的小分子抗登革病毒药物预测及其在药物再利用方面的意义。

Anti-Dengue: A Machine Learning-Assisted Prediction of Small Molecule Antivirals against Dengue Virus and Implications in Drug Repurposing.

机构信息

Virology Unit, Institute of Microbial Technology, Council of Scientific and Industrial Research (CSIR), Sector 39A, Chandigarh 160036, India.

Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.

出版信息

Viruses. 2023 Dec 27;16(1):45. doi: 10.3390/v16010045.

Abstract

Dengue outbreaks persist in global tropical regions, lacking approved antivirals, necessitating critical therapeutic development against the virus. In this context, we developed the "Anti-Dengue" algorithm that predicts dengue virus inhibitors using a quantitative structure-activity relationship (QSAR) and MLTs. Using the "DrugRepV" database, we extracted chemicals (small molecules) and repurposed drugs targeting the dengue virus with their corresponding IC values. Then, molecular descriptors and fingerprints were computed for these molecules using PaDEL software. Further, these molecules were split into training/testing and independent validation datasets. We developed regression-based predictive models employing 10-fold cross-validation using a variety of machine learning approaches, including SVM, ANN, kNN, and RF. The best predictive model yielded a of 0.71 on the training/testing dataset and 0.81 on the independent validation dataset. The created model's reliability and robustness were assessed using William's plot, scatter plot, decoy set, and chemical clustering analyses. Predictive models were utilized to identify possible drug candidates that could be repurposed. We identified goserelin, gonadorelin, and nafarelin as potential repurposed drugs with high pIC50 values. "Anti-Dengue" may be beneficial in accelerating antiviral drug development against the dengue virus.

摘要

登革热疫情在全球热带地区持续存在,而目前缺乏已批准的抗病毒药物,因此需要针对该病毒进行关键的治疗方法开发。在这种情况下,我们开发了“抗登革热”算法,该算法使用定量构效关系(QSAR)和 MLTs 来预测登革热病毒抑制剂。我们使用“DrugRepV”数据库,提取了针对登革热病毒的化学物质(小分子)和重新利用的药物及其相应的 IC 值。然后,使用 PaDEL 软件计算这些分子的分子描述符和指纹。进一步将这些分子分为训练/测试和独立验证数据集。我们使用各种机器学习方法(包括 SVM、ANN、kNN 和 RF),通过 10 倍交叉验证开发了基于回归的预测模型。在训练/测试数据集上,最佳预测模型的 AUC 为 0.71,在独立验证数据集上的 AUC 为 0.81。使用 William 图、散点图、诱饵集和化学聚类分析评估了所创建模型的可靠性和稳健性。使用预测模型来识别可能具有高 pIC50 值的可重新利用的候选药物。我们确定了戈舍瑞林、促性腺激素释放激素和那法瑞林是具有高 pIC50 值的潜在重新利用药物。“抗登革热”可能有助于加速针对登革热病毒的抗病毒药物开发。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d95a/10818795/8f03c3d4a205/viruses-16-00045-g001.jpg

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