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Canna~Fangled Abstracts

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

By October 9, 2021October 30th, 2021No Comments

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 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.

 

Keywords: COVID-19, Cannabinoids, Human iPSC-derived cardiomyocytes, SARS-Cov-2, WIN 55,212-2

Conflict of interest statement

Diogo Biagi, Estela M. Cruvinel and Rafael Dariolli are employed by Pluricell Biotech.

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Grant support

This work was supported by the National Council of Scientific and Technological Development (CNPq) (Grant Number: 313688/2020-6) and scholarship grants from Coordination for the Improvement of Higher Education Personnel (CAPES) and CNPq. Intramural grants were provided from the D’Or Institute for Research and Education (IDOR). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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