Abstract

The COVID-19 disease led to an unprecedented health emergency, still ongoing worldwide. Given the lack of a vaccine or a clear therapeutic strategy to counteract the infection as well as its secondary effects, there is currently a pressing need to generate new insights into the SARS-CoV-2 induced host response. Biomedical data can help to investigate new aspects of the COVID-19 pathogenesis, but source heterogeneity represents a major drawback and limitation. In this work, we applied data integration methods to develop a Unified Knowledge Space (UKS) and used it to identify a new set of genes associated with SARS-CoV-2 host response, both in vitro and in vivo. Functional analysis of these genes reveals possible long-term systemic effects of the infection, such as vascular remodelling and fibrosis. Finally, we identified a set of potentially relevant drugs targeting proteins involved in multiple steps of the host response to the virus.

Highlights

  • The newly identified coronavirus SARS-CoV-2 is responsible for a pandemic form of respiratory tract infection currently ongoing worldwide

  • By querying the Unified Knowledge Space (UKS), we derived a network of 20 793 human protein coding genes, represented as nodes, and 132 244 edges, representing the physical interaction relationships existing between the proteins encoded by the UKS gene nodes

  • Characterizing the cascade of events taking place at multiple levels in response to SARS-CoV-2 infection is urgently needed as the COVID-19 pandemic keeps rampaging worldwide

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Summary

Introduction

The newly identified coronavirus SARS-CoV-2 is responsible for a pandemic form of respiratory tract infection currently ongoing worldwide. Even if most patients remain asymptomatic or show mild symptoms, some develop complications, such as severe pneumonia and acute respiratory distress syndrome (ARDS) [1, 2]. Systemic complications, such as cardiovascular disorders, persistent lung injuries and possibly fibrosis are rapidly emerging as key threats in addition to the respiratory syndrome. A great effort is being made by the scientific community in order to develop new therapeutic approaches as well as to understand the molecular events characterizing the host response to SARS-CoV-2 infection. ACE2 is expressed in several organs and cell types, such as lung, heart, kidney, intestine and endothelial cells, which further raises concerns about possible ectopic effects of the infection [7]

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