{"doi":"10.1016/j.stemcr.2022.01.014","title":"Genome-wide analyses reveal the detrimental impacts of SARS-CoV-2 viral gene Orf9c on human pluripotent stem cell-derived cardiomyocytes","abstract":"Patients with coronavirus disease 2019 (COVID-19) commonly have manifestations of heart disease. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome encodes 27 proteins. Currently, SARS-CoV-2 gene-induced abnormalities of human heart muscle cells remain elusive. Here, we comprehensively characterized the detrimental effects of a SARS-CoV-2 gene, Orf9c, on human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) by preforming multi-omic analyses. Transcriptomic analyses of hPSC-CMs infected by SARS-CoV-2 with Orf9c overexpression (Orf9c OE ) identified concordantly up-regulated genes enriched into stress-related apoptosis and inflammation signaling pathways, and down-regulated CM functional genes. Proteomic analysis revealed enhanced expressions of apoptotic factors, whereas reduced protein factors for ATP synthesis by Orf9c OE . Orf9c OE significantly reduced cellular ATP level, induced apoptosis, and caused electrical dysfunctions of hPSC-CMs. Finally, drugs approved by the U.S. Food and Drug Administration, namely, ivermectin and meclizine, restored ATP levels and ameliorated CM death and functional abnormalities of Orf9c OE hPSC-CMs. Overall, we defined the molecular mechanisms underlying the detrimental impacts of Orf9c on hPSC-CMs and explored potentially therapeutic approaches to ameliorate Orf9c-induced cardiac injury and abnormalities.","journal":"Stem Cell Reports","year":2022,"id":274990,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.943,"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":944047,"name":"Yucheng Zhang","orcid":"0009-0003-0766-7115","position":1,"is_corresponding":false},{"id":458334,"name":"Lei Han","orcid":"0000-0002-7535-7915","position":2,"is_corresponding":false},{"id":399222,"name":"Shuai Guo","orcid":"0000-0002-9368-0548","position":3,"is_corresponding":false},{"id":737598,"name":"Shiyong Wu","orcid":"0000-0002-4104-4160","position":4,"is_corresponding":false},{"id":437389,"name":"Emma H. Doud","orcid":"0000-0003-0049-0073","position":5,"is_corresponding":false},{"id":274824,"name":"Cheng Wang","orcid":"0000-0002-7822-259X","position":6,"is_corresponding":false},{"id":944048,"name":"Hanying Chen","orcid":"0000-0002-7435-1423","position":7,"is_corresponding":false},{"id":448584,"name":"Michael Rubart‐von der Lohe","orcid":null,"position":8,"is_corresponding":false},{"id":300846,"name":"Jun Wan","orcid":"0000-0001-9286-6562","position":9,"is_corresponding":false},{"id":300845,"name":"Lei Yang","orcid":"0000-0002-1479-2374","position":10,"is_corresponding":false},{"id":303050,"name":"Juli Liu","orcid":null,"position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-19T00:28:16.928746Z","pmid":"35180394","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":[]}