Designing a Network Proximity-Based Drug Repurposing Strategy for COVID-19

The ongoing COVID-19 pandemic still requires fast and effective efforts from all fronts, including epidemiology, clinical practice, molecular medicine, and pharmacology. A comprehensive molecular framework of the disease is needed to better understand its pathological mechanisms, and to design succe...

Full description

Bibliographic Details
Main Authors: Paola Stolfi, Luigi Manni, Marzia Soligo, Davide Vergni, Paolo Tieri
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-10-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fcell.2020.545089/full
id doaj-79b6e58150b84750a491e3c40b083cca
record_format Article
spelling doaj-79b6e58150b84750a491e3c40b083cca2020-11-25T02:46:39ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2020-10-01810.3389/fcell.2020.545089545089Designing a Network Proximity-Based Drug Repurposing Strategy for COVID-19Paola Stolfi0Luigi Manni1Marzia Soligo2Davide Vergni3Paolo Tieri4National Research Council (CNR), Institute for Applied Computing (IAC), Rome, ItalyNational Research Council (CNR), Institute of Translational Pharmacology (IFT), Rome, ItalyNational Research Council (CNR), Institute of Translational Pharmacology (IFT), Rome, ItalyNational Research Council (CNR), Institute for Applied Computing (IAC), Rome, ItalyNational Research Council (CNR), Institute for Applied Computing (IAC), Rome, ItalyThe ongoing COVID-19 pandemic still requires fast and effective efforts from all fronts, including epidemiology, clinical practice, molecular medicine, and pharmacology. A comprehensive molecular framework of the disease is needed to better understand its pathological mechanisms, and to design successful treatments able to slow down and stop the impressive pace of the outbreak and harsh clinical symptomatology, possibly via the use of readily available, off-the-shelf drugs. This work engages in providing a wider picture of the human molecular landscape of the SARS-CoV-2 infection via a network medicine approach as the ground for a drug repurposing strategy. Grounding on prior knowledge such as experimentally validated host proteins known to be viral interactors, tissue-specific gene expression data, and using network analysis techniques such as network propagation and connectivity significance, the host molecular reaction network to the viral invasion is explored and exploited to infer and prioritize candidate target genes, and finally to propose drugs to be repurposed for the treatment of COVID-19. Ranks of potential target genes have been obtained for coherent groups of tissues/organs, potential and distinct sites of interaction between the virus and the organism. The normalization and the aggregation of the different scores allowed to define a preliminary, restricted list of genes candidates as pharmacological targets for drug repurposing, with the aim of contrasting different phases of the virus infection and viral replication cycle.https://www.frontiersin.org/article/10.3389/fcell.2020.545089/fullCOVID-19network medicinedrug repurposingnetwork-basedpharmacologic (drug) therapy
collection DOAJ
language English
format Article
sources DOAJ
author Paola Stolfi
Luigi Manni
Marzia Soligo
Davide Vergni
Paolo Tieri
spellingShingle Paola Stolfi
Luigi Manni
Marzia Soligo
Davide Vergni
Paolo Tieri
Designing a Network Proximity-Based Drug Repurposing Strategy for COVID-19
Frontiers in Cell and Developmental Biology
COVID-19
network medicine
drug repurposing
network-based
pharmacologic (drug) therapy
author_facet Paola Stolfi
Luigi Manni
Marzia Soligo
Davide Vergni
Paolo Tieri
author_sort Paola Stolfi
title Designing a Network Proximity-Based Drug Repurposing Strategy for COVID-19
title_short Designing a Network Proximity-Based Drug Repurposing Strategy for COVID-19
title_full Designing a Network Proximity-Based Drug Repurposing Strategy for COVID-19
title_fullStr Designing a Network Proximity-Based Drug Repurposing Strategy for COVID-19
title_full_unstemmed Designing a Network Proximity-Based Drug Repurposing Strategy for COVID-19
title_sort designing a network proximity-based drug repurposing strategy for covid-19
publisher Frontiers Media S.A.
series Frontiers in Cell and Developmental Biology
issn 2296-634X
publishDate 2020-10-01
description The ongoing COVID-19 pandemic still requires fast and effective efforts from all fronts, including epidemiology, clinical practice, molecular medicine, and pharmacology. A comprehensive molecular framework of the disease is needed to better understand its pathological mechanisms, and to design successful treatments able to slow down and stop the impressive pace of the outbreak and harsh clinical symptomatology, possibly via the use of readily available, off-the-shelf drugs. This work engages in providing a wider picture of the human molecular landscape of the SARS-CoV-2 infection via a network medicine approach as the ground for a drug repurposing strategy. Grounding on prior knowledge such as experimentally validated host proteins known to be viral interactors, tissue-specific gene expression data, and using network analysis techniques such as network propagation and connectivity significance, the host molecular reaction network to the viral invasion is explored and exploited to infer and prioritize candidate target genes, and finally to propose drugs to be repurposed for the treatment of COVID-19. Ranks of potential target genes have been obtained for coherent groups of tissues/organs, potential and distinct sites of interaction between the virus and the organism. The normalization and the aggregation of the different scores allowed to define a preliminary, restricted list of genes candidates as pharmacological targets for drug repurposing, with the aim of contrasting different phases of the virus infection and viral replication cycle.
topic COVID-19
network medicine
drug repurposing
network-based
pharmacologic (drug) therapy
url https://www.frontiersin.org/article/10.3389/fcell.2020.545089/full
work_keys_str_mv AT paolastolfi designinganetworkproximitybaseddrugrepurposingstrategyforcovid19
AT luigimanni designinganetworkproximitybaseddrugrepurposingstrategyforcovid19
AT marziasoligo designinganetworkproximitybaseddrugrepurposingstrategyforcovid19
AT davidevergni designinganetworkproximitybaseddrugrepurposingstrategyforcovid19
AT paolotieri designinganetworkproximitybaseddrugrepurposingstrategyforcovid19
_version_ 1724756838084247552