Activation of the urotensin-II receptor by remdesivir induces cardiomyocyte dysfunction.

ABSTRACT: Remdesivir is an antiviral drug used for COVID-19 treatment worldwide. Cardiovascular side effects have been associated with remdesivir; however, the underlying molecular mechanism remains unknown. Here, we performed a large-scale G-protein-coupled receptor screening in combination with structural modeling and found that remdesivir is a selective, partial agonist for urotensin-II receptor (UTS2R) through the Gα_i/o-dependent AKT/ERK axis. Functionally, remdesivir treatment induced prolonged field potential and APD₉₀ in human induced pluripotent stem cell (iPS)-derived cardiomyocytes and impaired contractility in both neonatal and adult cardiomyocytes, all of which mirror the clinical pathology. Importantly, remdesivir-mediated cardiac malfunctions were effectively atte

SUBMITTER: Ogawa A 

PROVIDER: S-EPMC10175918 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature