Network Medicine Framework for Identifying Drug Repurposing Opportunities for COVID-19

@article{Gysi2020NetworkMF,
  title={Network Medicine Framework for Identifying Drug Repurposing Opportunities for COVID-19},
  author={Deisy Morselli Gysi and {\`I}talo Faria do Valle and Marinka Zitnik and Asher Ameli and Xiao Gan and Onur Varol and Helia Sanchez and Rebecca Marlene Baron and Dina Ghiassian and Joseph Loscalzo and A L Barabasi},
  journal={ArXiv},
  year={2020}
}
The COVID-19 pandemic demands the rapid identification of drug-repurpusing candidates. In the past decade, network medicine had developed a framework consisting of a series of quantitative approaches and predictive tools to study host-pathogen interactions, unveil the molecular mechanisms of the infection, identify comorbidities as well as rapidly detect drug repurpusing candidates. Here, we adapt the network-based toolset to COVID-19, recovering the primary pulmonary manifestations of the… 

Figures and Tables from this paper

In silico drug repurposing in COVID-19: A network-based analysis
Heterogeneous network-based drug repurposing for COVID-19
TLDR
This paper presents a probabilistic analysis of the response of the immune system to data mining techniques and shows clear patterns in response to treatment-side effects of data mining.
Network-based repurposing identifies anti-alarmins as drug candidates to control severe lung inflammation in COVID-19
TLDR
A computational repurposing approach to identify candidate therapeutic drugs to control progression towards severe airways inflammation during COVID-19 confirmed the interest of dexamethasone, JAK2 inhibitors, estrogens and further identified various drugs either available or in development interacting with the aforementioned targets.
Dr-COVID: Graph Neural Networks for SARS-CoV-2 Drug Repurposing
TLDR
This work designs an encoder based on the scalable inceptive graph neural network (SIGN) to generate embeddings for all the nodes in the four-layered graph and proposes a quadratic norm scorer as a decoder to predict treatment for a disease.
Network analytics for drug repurposing in COVID-19
TLDR
This work constructed comprehensive directed protein–protein interaction (PPI) networks integrating the top-ranked host factors, the drug target proteins and directed PPI data to identify drug targets and combinations thereof that offer efficient control over the host factors.
COVID-19 Drug Repurposing: A Network-Based Framework for Exploring Biomedical Literature and Clinical Trials for Possible Treatments
TLDR
This paper investigates the hypothesis that a combination of FDA-approved drugs may be considered as a candidate for COVID-19 treatment if (1) there exists an evidence in the CO VID-19 biomedical literature that suggests such a combination, and (2) there is match in the clinical trials space that validates this drug combination.
A Network Medicine Approach to Investigation and Population-based Validation of Disease Manifestations and Drug Repurposing for COVID-19
TLDR
A network-based prediction and propensity score (PS) matching observational study of 18,118 patients from a COVID-19 registry identified that melatonin was associated with 64% reduced likelihood of a positive laboratory test result for SARS-CoV-2 and network proximity measure revealed underlying pathogenesis for broad CO VID-19-associated manifestations.
SAveRUNNER: A network-based algorithm for drug repurposing and its application to COVID-19
TLDR
A new network-based algorithm for drug repositioning, called SAveRUNNER (Searching off-lAbel dRUg aNd NEtwoRk), which predicts drug–disease associations by quantifying the interplay between the drug targets and the disease-specific proteins in the human interactome via a novel network- based similarity measure that prioritizes associations between drugs and diseases locating in the same network neighborhoods.
A Single-Cell Network-Based Drug Repositioning Strategy for Post-COVID-19 Pulmonary Fibrosis
TLDR
This work investigated COVID-19 patients’ transcriptome at single-cell resolution and combined biological network analyses to repurpose the drugs treating PCPF and revealed a novel gene signature of PCPF that is functionally associated with the viral infection and lung fibrosis.
...
...

References

SHOWING 1-10 OF 131 REFERENCES
Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2
TLDR
This study presents an integrative, antiviral drug repurposing methodology implementing a systems pharmacology-based network medicine platform, quantifying the interplay between the HCoV–host interactome and drug targets in the human protein–protein interaction network.
Exploring the SARS-CoV-2 virus-host-drug interactome for drug repurposing
TLDR
CoVex renders COVID-19 drug research systems-medicine-ready by giving the scientific community direct access to network medicine algorithms and investigates recent hypotheses on a systems biology level to explore mechanistic virus life cycle drivers, and to extract drug repurposing candidates.
Network-based approach to prediction and population-based validation of in silico drug repurposing
TLDR
It is demonstrated that a unique integration of protein-protein interaction network proximity and large-scale patient-level longitudinal data complemented by mechanistic in vitro studies can facilitate drug repurposing.
Network-based in silico drug efficacy screening
TLDR
This work introduces a drug-disease proximity measure that quantifies the interplay between drugs targets and diseases, and indicates that the therapeutic effect of drugs is localized in a small network neighborhood of the disease genes.
The Drug Repurposing Hub: a next-generation drug library and information resource
TLDR
This work hand-curated a collection of 4,707 compounds, experimentally confirmed their identities, and annotated them with literature-reported targets, to assemble a comprehensive library of drugs that have reached the clinic and established a blueprint for others to easily assemble such a repurposing library.
A genome-wide positioning systems network algorithm for in silico drug repurposing
TLDR
A network-based methodology to identify individualized disease modules by mapping patients’ DNA and RNA sequencing profiles to the interactome, enabling prediction of cancer type-specific drug responses and prediction of drug responses is introduced.
A SARS-CoV-2 Protein Interaction Map Reveals Targets for Drug-Repurposing
TLDR
A human–SARS-CoV-2 protein interaction map highlights cellular processes that are hijacked by the virus and that can be targeted by existing drugs, including inhibitors of mRNA translation and predicted regulators of the sigma receptors.
A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing
TLDR
The identification of host dependency factors mediating virus infection may provide key insights into effective molecular targets for developing broadly acting antiviral therapeutics against SARS-CoV-2 and other deadly coronavirus strains.
Network-based prediction of drug combinations
TLDR
A network-based methodology to identify efficacious drug combinations for specific diseases is proposed, and it is found that successful combinations tend to target separate neighbourhoods of the disease module in the human interactome.
Multidose evaluation of 6,710 drug repurposing library identifies potent SARS-CoV-2 infection inhibitors In Vitro and In Vivo.
TLDR
This work provides an important, publicly accessible, foundation for development of novel treatments for COVID-19, establishes human primary cell-based pharmacological models for evaluation of therapeutics and identifies new insights into SARS-CoV-2 infection mechanisms.
...
...