PeerJ · 2021
Inhibition of SARS-CoV-2 infection in human iPSC-derived cardiomyocytes by targeting the Sigma-1 receptor disrupts cytoarchitecture and beating.
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Salerno José Alexandre, Torquato Thayana, Temerozo Jairo R, Goto-Silva Livia, Karmirian Karina, Mendes Mayara A, Sacramento Carolina Q, Fintelman-Rodrigues Natalia, Souza Letícia R Q, Ornelas Isis M, Veríssimo Carla P, Aragão Luiz Guilherme H S, Vitória Gabriela, Pedrosa Carolina S G, da Silva Gomes Dias Suelen, Cardoso Soares Vinicius, Puig-Pijuan Teresa, Salazar Vinícius, Dariolli Rafael, Biagi Diogo, Furtado Daniel R, Barreto Chiarini Luciana, Borges Helena L, Bozza Patrícia T, Zaluar P Guimarães Marilia, Souza Thiago M L, Rehen Stevens K
Аннотация
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' integrity may abrogate its therapeutic potential against COVID and should be carefully considered.