SARS-CoV-2 meta-interactome suggests disease-specific, autoimmune pathophysiologies and therapeutic targets [version 1; peer review: 1 approved, 2 approved with reservations]
Background: Severe coronavirus disease 2019 (COVID-19) is associated with multiple comorbidities and is characterized by an auto-aggressive inflammatory state leading to massive collateral damage. To identify preventive and therapeutic strategies against severe acute respiratory syndrome coronavirus...
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doaj-2f1c5e6d666b4cdaab16cb5ae2b48fdf2021-01-12T18:06:33ZengF1000 Research LtdF1000Research2046-14022020-08-01910.12688/f1000research.25593.128245SARS-CoV-2 meta-interactome suggests disease-specific, autoimmune pathophysiologies and therapeutic targets [version 1; peer review: 1 approved, 2 approved with reservations]Gianmarco Bellucci0Chiara Ballerini1Rosella Mechelli2Rachele Bigi3Virginia Rinaldi4Roberta Reniè5Maria Chiara Buscarinu6Sergio E. Baranzini7Lohith Madireddy8Giuseppe Matarese9Marco Salvetti10Giovanni Ristori11Department of Neurosciences, Mental Health and Sensory Organs, Sapienza University of Rome, Rome, 00189, ItalyDepartment of Neurosciences, Mental Health and Sensory Organs, Sapienza University of Rome, Rome, 00189, ItalySan Raffaele Roma Open University; IRCCS San Raffaele Pisana, Rome, 00166, ItalyDepartment of Neurosciences, Mental Health and Sensory Organs, Sapienza University of Rome, Rome, 00189, ItalyDepartment of Neurosciences, Mental Health and Sensory Organs, Sapienza University of Rome, Rome, 00189, ItalyDepartment of Neurosciences, Mental Health and Sensory Organs, Sapienza University of Rome, Rome, 00189, ItalyDepartment of Neurosciences, Mental Health and Sensory Organs, Sapienza University of Rome, Rome, 00189, ItalyDepartment of Neurology, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, California, 94158, USADepartment of Neurology, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, California, 94158, USADipartimento di Medicina Molecolare e Biotecnologie Mediche, University of Naples Federico II, Naples, 80131, ItalyDepartment of Neurosciences, Mental Health and Sensory Organs, Sapienza University of Rome, Rome, 00189, ItalyDepartment of Neurosciences, Mental Health and Sensory Organs, Sapienza University of Rome, Rome, 00189, ItalyBackground: Severe coronavirus disease 2019 (COVID-19) is associated with multiple comorbidities and is characterized by an auto-aggressive inflammatory state leading to massive collateral damage. To identify preventive and therapeutic strategies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is important to ascertain the molecular interactions between virus and host, and how they translate into disease pathophysiology. Methods: We matched virus-human protein interactions of human coronaviruses and other respiratory viruses with lists of genes associated with autoimmune diseases and comorbidities associated to worse COVID-19 course. We then selected the genes included in the statistically significant intersection between SARS-CoV-2 network and disease associated gene sets, identifying a meta-interactome. We analyzed the meta-interactome genes expression in samples derived from lungs of infected humans, and their regulation by IFN-β. Finally, we performed a drug repurposing screening to target the network’s most critical nodes. Results: We found a significant enrichment of SARS-CoV-2 interactors in immunological pathways and a strong association with autoimmunity and three prognostically relevant conditions (type 2 diabetes, coronary artery diseases, asthma), that present more independent physiopathological subnetworks. We observed a reduced expression of meta-interactome genes in human lungs after SARS-CoV-2 infection, and a regulatory potential of type I interferons. We also underscored multiple repurposable drugs to tailor the therapeutic strategies. Conclusions: Our data underscored a plausible genetic background that may contribute to the distinct observed pathophysiologies of severe COVID-19. Also, these results may help identify the most promising therapeutic targets and treatments for this condition.https://f1000research.com/articles/9-992/v1 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Gianmarco Bellucci Chiara Ballerini Rosella Mechelli Rachele Bigi Virginia Rinaldi Roberta Reniè Maria Chiara Buscarinu Sergio E. Baranzini Lohith Madireddy Giuseppe Matarese Marco Salvetti Giovanni Ristori |
spellingShingle |
Gianmarco Bellucci Chiara Ballerini Rosella Mechelli Rachele Bigi Virginia Rinaldi Roberta Reniè Maria Chiara Buscarinu Sergio E. Baranzini Lohith Madireddy Giuseppe Matarese Marco Salvetti Giovanni Ristori SARS-CoV-2 meta-interactome suggests disease-specific, autoimmune pathophysiologies and therapeutic targets [version 1; peer review: 1 approved, 2 approved with reservations] F1000Research |
author_facet |
Gianmarco Bellucci Chiara Ballerini Rosella Mechelli Rachele Bigi Virginia Rinaldi Roberta Reniè Maria Chiara Buscarinu Sergio E. Baranzini Lohith Madireddy Giuseppe Matarese Marco Salvetti Giovanni Ristori |
author_sort |
Gianmarco Bellucci |
title |
SARS-CoV-2 meta-interactome suggests disease-specific, autoimmune pathophysiologies and therapeutic targets [version 1; peer review: 1 approved, 2 approved with reservations] |
title_short |
SARS-CoV-2 meta-interactome suggests disease-specific, autoimmune pathophysiologies and therapeutic targets [version 1; peer review: 1 approved, 2 approved with reservations] |
title_full |
SARS-CoV-2 meta-interactome suggests disease-specific, autoimmune pathophysiologies and therapeutic targets [version 1; peer review: 1 approved, 2 approved with reservations] |
title_fullStr |
SARS-CoV-2 meta-interactome suggests disease-specific, autoimmune pathophysiologies and therapeutic targets [version 1; peer review: 1 approved, 2 approved with reservations] |
title_full_unstemmed |
SARS-CoV-2 meta-interactome suggests disease-specific, autoimmune pathophysiologies and therapeutic targets [version 1; peer review: 1 approved, 2 approved with reservations] |
title_sort |
sars-cov-2 meta-interactome suggests disease-specific, autoimmune pathophysiologies and therapeutic targets [version 1; peer review: 1 approved, 2 approved with reservations] |
publisher |
F1000 Research Ltd |
series |
F1000Research |
issn |
2046-1402 |
publishDate |
2020-08-01 |
description |
Background: Severe coronavirus disease 2019 (COVID-19) is associated with multiple comorbidities and is characterized by an auto-aggressive inflammatory state leading to massive collateral damage. To identify preventive and therapeutic strategies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is important to ascertain the molecular interactions between virus and host, and how they translate into disease pathophysiology. Methods: We matched virus-human protein interactions of human coronaviruses and other respiratory viruses with lists of genes associated with autoimmune diseases and comorbidities associated to worse COVID-19 course. We then selected the genes included in the statistically significant intersection between SARS-CoV-2 network and disease associated gene sets, identifying a meta-interactome. We analyzed the meta-interactome genes expression in samples derived from lungs of infected humans, and their regulation by IFN-β. Finally, we performed a drug repurposing screening to target the network’s most critical nodes. Results: We found a significant enrichment of SARS-CoV-2 interactors in immunological pathways and a strong association with autoimmunity and three prognostically relevant conditions (type 2 diabetes, coronary artery diseases, asthma), that present more independent physiopathological subnetworks. We observed a reduced expression of meta-interactome genes in human lungs after SARS-CoV-2 infection, and a regulatory potential of type I interferons. We also underscored multiple repurposable drugs to tailor the therapeutic strategies. Conclusions: Our data underscored a plausible genetic background that may contribute to the distinct observed pathophysiologies of severe COVID-19. Also, these results may help identify the most promising therapeutic targets and treatments for this condition. |
url |
https://f1000research.com/articles/9-992/v1 |
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