tetano
Editor, Senior Moderator
F1000Res
. 2020 Aug 17;9:992.
doi: 10.12688/f1000research.25593.1. eCollection 2020.
SARS-CoV-2 meta-interactome suggests disease-specific, autoimmune pathophysiologies and therapeutic targets
Gianmarco Bellucci[SUP] 1 [/SUP], Chiara Ballerini[SUP] 1 [/SUP], Rosella Mechelli[SUP] 2 [/SUP], Rachele Bigi[SUP] 1 [/SUP], Virginia Rinaldi[SUP] 1 [/SUP], Roberta Reni?[SUP] 1 [/SUP], Maria Chiara Buscarinu[SUP] 1 [/SUP], Sergio E Baranzini[SUP] 3 [/SUP], Lohith Madireddy[SUP] 3 [/SUP], Giuseppe Matarese[SUP] 4 5 [/SUP], Marco Salvetti[SUP] 1 6 [/SUP], Giovanni Ristori[SUP] 1 [/SUP]
Affiliations
Abstract
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.
Keywords: COVID-19; SARS-CoV-2; autoimmune disease; interferon; protein-protein interaction; repurposing; virus.
. 2020 Aug 17;9:992.
doi: 10.12688/f1000research.25593.1. eCollection 2020.
SARS-CoV-2 meta-interactome suggests disease-specific, autoimmune pathophysiologies and therapeutic targets
Gianmarco Bellucci[SUP] 1 [/SUP], Chiara Ballerini[SUP] 1 [/SUP], Rosella Mechelli[SUP] 2 [/SUP], Rachele Bigi[SUP] 1 [/SUP], Virginia Rinaldi[SUP] 1 [/SUP], Roberta Reni?[SUP] 1 [/SUP], Maria Chiara Buscarinu[SUP] 1 [/SUP], Sergio E Baranzini[SUP] 3 [/SUP], Lohith Madireddy[SUP] 3 [/SUP], Giuseppe Matarese[SUP] 4 5 [/SUP], Marco Salvetti[SUP] 1 6 [/SUP], Giovanni Ristori[SUP] 1 [/SUP]
Affiliations
- PMID: 33456761
- PMCID: PMC7791351
- DOI: 10.12688/f1000research.25593.1
Abstract
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.
Keywords: COVID-19; SARS-CoV-2; autoimmune disease; interferon; protein-protein interaction; repurposing; virus.