Inhibition of SARS-CoV-2 infection in human cardiomyocytes by targeting the Sigma-1 receptor disrupts cytoskeleton architecture and contractility

Salerno, José Alexandre; Torquato, Thayana; Temerozo, Jairo R.; Goto‐Silva, Livia; Mendes, Mayara Abud; Sacramento, Carolina Q.; Fintelman-Rodrigues, Natália; Vitória, Gabriela; Souza, Letícia R. Q.; Ornelas, Isis M.; Veríssimo, Carla Pires; Karmirian, Karina; Pedrosa, Carolina da S. G.; Dias, Suelen da Silva Gomes; Soares, Vinícius Cardoso; Aragão, Luiz Guilherme H.S.; Puig‐Pijuan, Teresa; Salazar, Vinícius; Dariolli, Rafael; Biagi, Diogo; Furtado, Daniel Rodrigues; Borges, Helena L.; Bozza, Patrı́cia T.; Guimarães, Marília Zaluar P.; Souza, Thiago Moreno L.; Rehen, Stevens

doi:10.1101/2021.02.20.432092

Cited by 3 publications

(4 citation statements)

References 99 publications

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“…S4). hiPSC-CMs were handled in four different groups: MOCK and SARS-CoV-2 (SARS-CoV-2 infection without WIN), which were also analyzed as controls in Salerno et al (2021), MOCK WIN (no SARS-CoV-2 infection + WIN), and SARS-CoV-2 WIN (SARS-Cov-2 infection + WIN). All WIN-treated hiPSC-CMs were pretreated for 24 h with one µM WIN.…”

Section: Ips-cardiomyocyte Differentiation and Purificationmentioning

confidence: 99%

“…After confirming that hiPSC-CMs express CB1 and ACE2 (Salerno et al, 2021), we asked whether WIN modulates ACE2 expression and, subsequently, influences SARS-CoV-2 infection within hiPSC-CMs. The cells were pretreated with one µM WIN for 24 h and analyzed for both mRNA and protein levels of ACE2.…”

Section: Human Cardiomyocytes Express Cannabinoid Receptor 1 But Win Does Not Modulate Ace2 Expressionmentioning

confidence: 99%

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

Aragão

Oliveira

Temerozo

et al. 2021

PeerJ

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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 lead to 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 six, eight, 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.

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Section: Ips-cardiomyocyte Differentiation and Purificationmentioning

confidence: 99%

Section: Human Cardiomyocytes Express Cannabinoid Receptor 1 But Win Does Not Modulate Ace2 Expressionmentioning

confidence: 99%

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

Aragão

Oliveira

Temerozo

et al. 2021

PeerJ

Self Cite

View full text Add to dashboard Cite

show abstract

“…After confirming that hiPSC-CMs express CB1 and ACE2 (Salerno et al, 2021), we asked whether WIN modulates ACE2 expression and, subsequently, influences…”

Section: Human Cardiomyocytes Express Cannabinoid Receptor But Win Does Not Modulate Ace2 Expressionmentioning

confidence: 99%

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

Aragão

Oliveira

Temerozo

et al. 2021

Preprint

Self Cite

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Coronavirus disease 2019 (COVID-19) is caused by acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can infect several organs and lead to loss of vital organ function, especially impacting respiratory capacity. Among the extrapulmonary manifestations of COVID-19 is myocardial injury, caused both directly and indirectly by SARS-CoV-2, and which is associated with a high risk of mortality. One of the hallmarks of severe COVID-19 is the cytokine storm, at which point the immune system malfunctions, leading to possible organ failure and death. 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) on SARS-CoV-2-infected human iPSC-derived cardiomyocytes (hiPSC-CMs). Although WIN did not modulate angiotensin-converting enzyme II, nor reduced SARS-CoV-2 infection and replication in hiPSC-CMs at the conditions tested, it had anti-inflammatory and protective effects by reducing the levels of interleukins 6, 8,18 and tumor necrosis factor-alpha (TNF-α) and lactate dehydrogenase (LDH) activity in these cells without causing hypertrophic cardiac damage. These findings suggest that cannabinoids should be further investigated as an alternative therapeutic tool for the treatment of COVID-19.

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“… 3 The argument is supported by the observation that Sig-1R antagonist NE-100 inhibited SARS-CoV-2 infection and replication in human cardiomyocytes, but also disrupted cytoskeletal architecture and contractility. 13 …”

mentioning

confidence: 99%

Anaesthesia drugs, SARS-CoV-2, and the sigma-1 receptor: a complex affair. Comment on Br J Anaesth 2021; 127: e32–4

Jain¹,

Lamperti²,

Doyle

et al. 2021

British Journal of Anaesthesia

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Inhibition of SARS-CoV-2 infection in human cardiomyocytes by targeting the Sigma-1 receptor disrupts cytoskeleton architecture and contractility

Cited by 3 publications

References 99 publications

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

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

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

Anaesthesia drugs, SARS-CoV-2, and the sigma-1 receptor: a complex affair. Comment on Br J Anaesth 2021; 127: e32–4

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