{"doi":"10.1101/2020.11.03.366666","title":"Looking for pathways related to COVID-19 phenotypes: Confirmation of pathogenic mechanisms by SARS-CoV-2 - Host interactome","abstract":"Abstract In the last months, many studies have clearly described several mechanisms of SARS-CoV-2 infection at cell and tissue level. Host conditions and comorbidities were identified as risk factors for severe and fatal disease courses, but the mechanisms of interaction between host and SARS-CoV-2 determining the grade of COVID- 19 severity, are still unknown. We provide a network analysis on protein–protein interactions (PPI) between viral and host proteins to better identify host biological responses, induced by both whole proteome of SARS-CoV-2 and specific viral proteins. A host-virus interactome was inferred on published PPI, using an explorative algorithm (Random Walk with Restart) triggered by all the 28 proteins of SARS-CoV-2, or each single viral protein one-by-one. The functional analysis for all proteins, linked to many aspects of COVID-19 pathogenesis, allows to identify the subcellular districts, where SARS-CoV-2 proteins seem to be distributed, while in each interactome built around one single viral protein, a different response was described, underlining as ORF8 and ORF3a modulated cardiovascular diseases and pro-inflammatory pathways, respectively. Finally, an explorative network-based approach was applied to Bradykinin Storm, highlighting a possible direct action of ORF3a and NS7b to enhancing this condition. This network-based model for SARS-CoV-2 infection could be a framework for pathogenic evaluation of specific clinical outcomes. We identified possible host responses induced by specific proteins of SARS-CoV-2, underlining the important role of specific viral accessory proteins in pathogenic phenotypes of severe COVID-19 patients.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":122357,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8818,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":247270,"name":"Emanuela Giombini","orcid":"0000-0003-2237-9755","position":1,"is_corresponding":false},{"id":314578,"name":"Chiara Montaldo","orcid":"0000-0001-7346-7507","position":2,"is_corresponding":false},{"id":245500,"name":"Ashish Sharma","orcid":"0000-0002-1011-6504","position":3,"is_corresponding":false},{"id":240148,"name":"Mauro Piacentini","orcid":"0000-0003-2919-1296","position":4,"is_corresponding":false},{"id":10807,"name":"A. Zoccoli","orcid":"0000-0002-0993-6185","position":5,"is_corresponding":false},{"id":244983,"name":"Rafick‐Pierre Sékaly","orcid":"0000-0002-7816-4828","position":6,"is_corresponding":false},{"id":228967,"name":"Franco Locatelli","orcid":"0000-0002-7976-3654","position":7,"is_corresponding":false},{"id":85550,"name":"Alimuddin Zumla","orcid":"0000-0002-5111-5735","position":8,"is_corresponding":false},{"id":228081,"name":"Markus Maeurer","orcid":"0000-0002-8436-8077","position":9,"is_corresponding":false},{"id":85541,"name":"Maria Rosaria Capobianchi","orcid":"0000-0003-3465-0071","position":10,"is_corresponding":false},{"id":449033,"name":"F. Lauria","orcid":"0000-0001-8621-8841","position":11,"is_corresponding":false},{"id":85534,"name":"Giuseppe Ippolito","orcid":"0000-0002-1076-2979","position":12,"is_corresponding":false},{"id":564069,"name":"COVID 19 INMI Network Medicine for IDs Study Group.","orcid":null,"position":13,"is_corresponding":false},{"id":492165,"name":"Francesco Messina","orcid":"0000-0001-8076-7217","position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":null,"created_at":"2026-07-18T23:14:51.076430Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}