WIN 55,212-2 shows anti-inflammatory and survival properties in human iPSC-derived cardiomyocytes infected with SARS-CoV-2

Aragão, Luiz Guilherme H. S.; Oliveira, Júlia T.; Temerozo, Jairo R.; Mendes, Mayara A.; Salerno, José Alexandre; Pedrosa, Carolina da S. G.; Puig-Pijuan, Teresa; Veríssimo, Carla P.; Ornelas, Isis M.; Torquato, Thayana; Vitória, Gabriela; Sacramento, Carolina Q.; Fintelman-Rodrigues, Natalia; Dias, Suelen da Silva Gomes; Soares, Vinicius Cardoso; Souza, Leticia R. Q.; Karmirian, Karina; Goto-Silva, Livia; Biagi, Diogo; Cruvinel, Estela M.; Dariolli, Rafael; Furtado, Daniel R.; Bozza, Patrícia T.; Borges, Helena L.; Souza, Thiago Moreno L.; Guimarães, Marília Zaluar P.; Rehen, Stevens

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can infect several organs, especially impacting respiratory capacity. Among the extrapulmonary manifestations of COVID-19 is myocardial injury, which is associated with a high risk of mortality. Myocardial injury, caused directly or indirectly by SARS-CoV-2 infection, can be triggered by inflammatory processes that cause damage to the heart tissue. Since one of the hallmarks of severe COVID-19 is the “cytokine storm”, strategies to control inflammation caused by SARS-CoV-2 infection have been considered. Cannabinoids are known to have anti-inflammatory properties by negatively modulating the release of pro-inflammatory cytokines. Herein, we investigated the effects of the cannabinoid agonist WIN 55,212-2 (WIN) in human iPSC-derived cardiomyocytes (hiPSC-CMs) infected with SARS-CoV-2. WIN did not modify angiotensin-converting enzyme II protein levels, nor reduced viral infection and replication in hiPSC-CMs. On the other hand, WIN reduced the levels of interleukins 6, 8, 18 and tumor necrosis factor-alpha (TNF-α) released by infected cells, and attenuated cytotoxic damage measured by the release of lactate dehydrogenase (LDH). Our findings suggest that cannabinoids should be further explored as a complementary therapeutic tool for reducing inflammation in COVID-19 patients.