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以宿主为中心的病毒疾病药物再利用

Host centric drug repurposing for viral diseases.

作者信息

de Siqueira Santos Suzana, Yang Haixuan, Galeano Aldo, Paccanaro Alberto

机构信息

Escola de Matemática Aplicada, Fundação Getúlio Vargas, Rio de Janeiro, Brazil.

School of Mathematical & Statistical Sciences, University of Galway, Galway, Ireland.

出版信息

PLoS Comput Biol. 2025 Apr 2;21(4):e1012876. doi: 10.1371/journal.pcbi.1012876. eCollection 2025 Apr.

Abstract

Computational approaches for drug repurposing for viral diseases have mainly focused on a small number of antivirals that directly target pathogens (virus centric therapies). In this work, we combine ideas from collaborative filtering and network medicine for making predictions on a much larger set of drugs that could be repurposed for host centric therapies, that are aimed at interfering with host cell factors required by a pathogen. Our idea is to create matrices quantifying the perturbation that drugs and viruses induce on human protein interaction networks. Then, we decompose these matrices to learn embeddings of drugs, viruses, and proteins in a low dimensional space. Predictions of host-centric antivirals are obtained by taking the dot product between the corresponding drug and virus representations. Our approach is general and can be applied systematically to any compound with known targets and any virus whose host proteins are known. We show that our predictions have high accuracy and that the embeddings contain meaningful biological information that may provide insights into the underlying biology of viral infections. Our approach can integrate different types of information, does not rely on known drug-virus associations and can be applied to new viral diseases and drugs.

摘要

用于病毒疾病药物重新定位的计算方法主要集中在少数直接针对病原体的抗病毒药物上(以病毒为中心的疗法)。在这项工作中,我们结合了协同过滤和网络医学的理念,对更多可用于以宿主为中心的疗法的药物进行预测,这些疗法旨在干扰病原体所需的宿主细胞因子。我们的想法是创建量化药物和病毒对人类蛋白质相互作用网络诱导的扰动的矩阵。然后,我们分解这些矩阵以在低维空间中学习药物、病毒和蛋白质的嵌入。通过取相应药物和病毒表示之间的点积来获得以宿主为中心的抗病毒药物的预测。我们的方法具有通用性,可以系统地应用于任何具有已知靶点的化合物和任何宿主蛋白已知的病毒。我们表明我们的预测具有很高的准确性,并且嵌入包含有意义的生物学信息,这可能为病毒感染的潜在生物学提供见解。我们的方法可以整合不同类型的信息,不依赖于已知的药物 - 病毒关联,并且可以应用于新的病毒性疾病和药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c67d/12052139/0ea3ee629e09/pcbi.1012876.g001.jpg

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