{"doi":"10.1371/journal.pbio.3001851","title":"Hippo signaling pathway activation during SARS-CoV-2 infection contributes to host antiviral response","abstract":"Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), responsible for the Coronavirus Disease 2019 (COVID-19) pandemic, causes respiratory failure and damage to multiple organ systems. The emergence of viral variants poses a risk of vaccine failures and prolongation of the pandemic. However, our understanding of the molecular basis of SARS-CoV-2 infection and subsequent COVID-19 pathophysiology is limited. In this study, we have uncovered a critical role for the evolutionarily conserved Hippo signaling pathway in COVID-19 pathogenesis. Given the complexity of COVID-19-associated cell injury and immunopathogenesis processes, we investigated Hippo pathway dynamics in SARS-CoV-2 infection by utilizing COVID-19 lung samples and human cell models based on pluripotent stem cell-derived cardiomyocytes (PSC-CMs) and human primary lung air-liquid interface (ALI) cultures. SARS-CoV-2 infection caused activation of the Hippo signaling pathway in COVID-19 lung and in vitro cultures. Both parental and Delta variant of concern (VOC) strains induced Hippo pathway. The chemical inhibition and gene knockdown of upstream kinases MST1/2 and LATS1 resulted in significantly enhanced SARS-CoV-2 replication, indicating antiviral roles. Verteporfin, a pharmacological inhibitor of the Hippo pathway downstream transactivator, YAP, significantly reduced virus replication. These results delineate a direct antiviral role for Hippo signaling in SARS-CoV-2 infection and the potential for this pathway to be pharmacologically targeted to treat COVID-19.","journal":"PLoS Biology","year":2022,"id":240575,"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":45,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9514,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":869247,"name":"Arjit Vijey Jeyachandran","orcid":null,"position":1,"is_corresponding":false},{"id":291456,"name":"Yijie Wang","orcid":"0000-0002-2681-0138","position":2,"is_corresponding":false},{"id":869248,"name":"Joseph Ignatius Irudayam","orcid":null,"position":3,"is_corresponding":false},{"id":869249,"name":"Sebastian Castillo Cario","orcid":null,"position":4,"is_corresponding":false},{"id":284473,"name":"Chandani Sen","orcid":"0000-0003-4112-7473","position":5,"is_corresponding":false},{"id":653311,"name":"Li Shen","orcid":"0000-0002-5696-2191","position":6,"is_corresponding":false},{"id":868593,"name":"Yunfeng Li","orcid":"0000-0002-6520-8561","position":7,"is_corresponding":false},{"id":273583,"name":"Ashok Kumar","orcid":"0000-0001-6332-6591","position":8,"is_corresponding":false},{"id":305511,"name":"Karin Nielsen‐Saines","orcid":"0000-0002-1742-5211","position":9,"is_corresponding":false},{"id":319807,"name":"Samuel W. French","orcid":"0000-0002-7611-881X","position":10,"is_corresponding":false},{"id":568702,"name":"Priya S. Shah","orcid":"0000-0001-7518-2839","position":11,"is_corresponding":false},{"id":232371,"name":"Kouki Morizono","orcid":"0000-0001-5601-3992","position":12,"is_corresponding":false},{"id":284480,"name":"Brigitte N. Gomperts","orcid":"0000-0002-1809-723X","position":13,"is_corresponding":false},{"id":244631,"name":"Arjun Deb","orcid":"0000-0003-0978-2611","position":14,"is_corresponding":false},{"id":245847,"name":"Arunachalam Ramaiah","orcid":"0000-0003-3573-6141","position":15,"is_corresponding":false},{"id":232372,"name":"Vaithilingaraja Arumugaswami","orcid":"0000-0002-6872-5118","position":16,"is_corresponding":false},{"id":232368,"name":"Gustavo Garcia","orcid":"0000-0002-1649-9251","position":0,"is_corresponding":true}],"reference_count":64,"raw_metadata":null,"created_at":"2026-07-19T00:22:51.435773Z","pmid":"36346780","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":[]}