Host centric drug repurposing for viral diseases

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.