A cannabinoid receptor agonist shows anti-inflammatory and survival properties in human SARS-CoV-2-infected iPSC-derived cardiomyocytes

Aragao, L. G. H. S.; Oliveira, J. T.; Temerozo, J. R.; Mendes, M. A.; Salerno, J. A.; Pedrosa, C. d. S. G.; Puig-Pijuan, T.; Verissimo, C.; Ornelas, I. M.; Torquato, T.; Vitoria, G.; Sacramento, C. Q.; Fintelman-Rodrigues, N.; Dias, S. d. S. G.; Cardoso Soares, V.; Souza, L. R. Q.; Karmirian, K.; Goto-Silva, L.; Biagi, D.; Cruvinel, E. M.; Dariolli, R.; Furtado, D. R.; Bozza, P. T.; Borges, H. L.; Souza, T. M. L.; Guimaraes, M. Z. P.; Rehen, S.

doi:10.1101/2021.02.20.431855

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bioRxiv · 10.1101/2021.02.20.431855

A cannabinoid receptor agonist shows anti-inflammatory and survival properties in human SARS-CoV-2-infected iPSC-derived cardiomyocytes

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Abstract

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-) 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.

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Aragao, L. G. H. S., Oliveira, J. T., Temerozo, J. R., Mendes, M. A., Salerno, J. A., Pedrosa, C. d. S. G., Puig-Pijuan, T., Verissimo, C., Ornelas, I. M., Torquato, T., Vitoria, G., Sacramento, C. Q., Fintelman-Rodrigues, N., Dias, S. d. S. G., Cardoso Soares, V., Souza, L. R. Q., Karmirian, K., Goto-Silva, L., Biagi, D., Cruvinel, E. M., Dariolli, R., Furtado, D. R., Bozza, P. T., Borges, H. L., Souza, T. M. L., Guimaraes, M. Z. P., Rehen, S.. 2021-02-21. A cannabinoid receptor agonist shows anti-inflammatory and survival properties in human SARS-CoV-2-infected iPSC-derived cardiomyocytes. https://doi.org/10.1101/2021.02.20.431855

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