Cardio- and Neurotoxicity of Selected Anti-COVID-19 Drugs.

Autor: Nicholson MW; Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan., Huang CY; Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan., Wang JY; Genomics Research Center, Academia Sinica, Taipei 115, Taiwan., Ting CY; Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan., Cheng YC; Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan., Chan DZH; Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan., Lee YC; Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan., Hsu CC; Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan., Hsu YH; Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan., Chang CMC; Cardiovascular Physiology Core Facility, Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA., Hsieh ML; Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.; Cardiovascular Physiology Core Facility, Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA., Cheng YY; Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan., Lin YL; Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan., Chen CH; Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan., Wu YT; Genomics Research Center, Academia Sinica, Taipei 115, Taiwan., Hacker TA; Cardiovascular Physiology Core Facility, Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA., Wu JC; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA., Kamp TJ; Department of Medicine and Stem Cell and Regenerative Medicine Center, University of Wisconsin-Madison, Madison, WI 53705, USA., Hsieh PCH; Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.; Department of Medicine and Stem Cell and Regenerative Medicine Center, University of Wisconsin-Madison, Madison, WI 53705, USA.; Institute of Clinical Medicine, National Taiwan University, Taipei 106, Taiwan.
Jazyk: angličtina
Zdroj: Pharmaceuticals (Basel, Switzerland) [Pharmaceuticals (Basel)] 2022 Jun 20; Vol. 15 (6). Date of Electronic Publication: 2022 Jun 20.
DOI: 10.3390/ph15060765
Abstrakt: Since December 2019, the novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected ~435 million people and caused ~6 million related deaths as of March 2022. To combat COVID-19, there have been many attempts to repurpose FDA-approved drugs or revive old drugs. However, many of the current treatment options have been known to cause adverse drug reactions. We employed a population-based drug screening platform using 13 human leukocyte antigen (HLA) homozygous human induced pluripotent cell (iPSC) lines to assess the cardiotoxicity and neurotoxicity of the first line of anti-COVID-19 drugs. We also infected iPSC-derived cells to understand the viral infection of cardiomyocytes and neurons. We found that iPSC-derived cardiomyocytes express the ACE2 receptor which correlated with a higher infection of the SARS-CoV-2 virus (r = 0.86). However, we were unable to detect ACE2 expression in neurons which correlated with a low infection rate. We then assessed the toxicity of anti-COVID-19 drugs and identified two cardiotoxic compounds (remdesivir and arbidol) and four neurotoxic compounds (arbidol, remdesivir, hydroxychloroquine, and chloroquine). These data show that this platform can quickly and easily be employed to further our understanding of cell-specific infection and identify drug toxicity of potential treatment options helping clinicians better decide on treatment options.
Databáze: MEDLINE
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