{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T08:43:39Z","timestamp":1772268219172,"version":"3.50.1"},"reference-count":94,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T00:00:00Z","timestamp":1639958400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"D\u2019Or Institute for Research and Education"},{"name":"The Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES) or Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>SARS-CoV-2 infects cardiac cells and causes heart dysfunction. Conditions such as myocarditis and arrhythmia have been reported in COVID-19 patients. The Sigma-1 receptor (S1R) is a ubiquitously expressed chaperone that plays a central role in cardiomyocyte function. S1R has been proposed as a therapeutic target because it may affect SARS-CoV-2 replication; however, the impact of the inhibition of S1R in human cardiomyocytes remains to be described. In this study, we investigated the consequences of S1R inhibition in iPSC-derived human cardiomyocytes (hiPSC-CM). SARS-CoV-2 infection in hiPSC-CM was productive and reduced cell survival. S1R inhibition decreased both the number of infected cells and viral particles after 48 hours. S1R inhibition also prevented the release of pro-inflammatory cytokines and cell death. Although the S1R antagonist NE-100 triggered those protective effects, it compromised cytoskeleton integrity by downregulating the expression of structural-related genes and reducing beating frequency. Our findings suggest that the detrimental effects of S1R inhibition in human cardiomyocytes\u2019 integrity may abrogate its therapeutic potential against COVID and should be carefully considered.<\/jats:p>","DOI":"10.7717\/peerj.12595","type":"journal-article","created":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T05:02:21Z","timestamp":1639976541000},"page":"e12595","source":"Crossref","is-referenced-by-count":5,"title":["Inhibition of SARS-CoV-2 infection in human iPSC-derived cardiomyocytes by targeting the Sigma-1 receptor disrupts cytoarchitecture and beating"],"prefix":"10.7717","volume":"9","author":[{"given":"Jos\u00e9 Alexandre","family":"Salerno","sequence":"first","affiliation":[{"name":"Institute of Biomedical Sciences, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil"},{"name":"D\u2019Or Institute for Research and Education (IDOR), Rio de Janeiro, 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