Host centric drug repurposing for viral diseases

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.

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Publication Details

Journal
PLoS Computational Biology
Published
2025-04-02
DOI
https://doi.org/10.1371/journal.pcbi.1012876
Primary Topic
Computational Drug Discovery Methods
Type
article
Field-Weighted Citation Impact
0.00

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article

Host centric drug repurposing for viral diseases

Suzana de Siqueira Santos, Alberto Paccanaro, Haixuan Yang, Aldo Galeano
PLoS Computational Biology
Computational Drug Discovery Methods
article

Host centric drug repurposing for viral diseases

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

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.

PLoS Computational BiologyVol. 21(4)
Royal Holloway University of London (GB), Ollscoil na Gaillimhe – University of Galway (IE), Fundação Getulio Vargas (BR)
National Science Foundation, Fundação Getulio Vargas, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro, Consejo Nacional de Ciencia y Tecnología, Paraguay, Medical Research Council, Biotechnology and Biological Sciences Research Council
Openalex Percentile: Top 93%
Computational Drug Discovery Methods
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