PMID- 35745684
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 1424-8247 (Print)
IS  - 1424-8247 (Electronic)
IS  - 1424-8247 (Linking)
VI  - 15
IP  - 6
DP  - 2022 Jun 20
TI  - Cardio- and Neurotoxicity of Selected Anti-COVID-19 Drugs.
LID - 10.3390/ph15060765 [doi]
LID - 765
AB  - 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.
FAU - Nicholson, Martin W
AU  - Nicholson MW
AD  - Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
FAU - Huang, Ching-Ying
AU  - Huang CY
AD  - Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
FAU - Wang, Jyun-Yuan
AU  - Wang JY
AD  - Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
FAU - Ting, Chien-Yu
AU  - Ting CY
AUID- ORCID: 0000-0002-9168-5820
AD  - Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
FAU - Cheng, Yu-Che
AU  - Cheng YC
AD  - Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
FAU - Chan, Darien Z H
AU  - Chan DZH
AD  - Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
FAU - Lee, Yi-Chan
AU  - Lee YC
AUID- ORCID: 0000-0003-0276-4664
AD  - Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
FAU - Hsu, Ching-Chuan
AU  - Hsu CC
AD  - Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
FAU - Hsu, Yu-Hung
AU  - Hsu YH
AD  - Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
FAU - Chang, Cindy M C
AU  - Chang CMC
AD  - Cardiovascular Physiology Core Facility, Department of Medicine, University of 
      Wisconsin-Madison, Madison, WI 53705, USA.
FAU - Hsieh, Marvin L
AU  - Hsieh ML
AD  - Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
AD  - Cardiovascular Physiology Core Facility, Department of Medicine, University of 
      Wisconsin-Madison, Madison, WI 53705, USA.
FAU - Cheng, Yuan-Yuan
AU  - Cheng YY
AD  - Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
FAU - Lin, Yi-Ling
AU  - Lin YL
AUID- ORCID: 0000-0002-1838-6410
AD  - Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
FAU - Chen, Chien-Hsiun
AU  - Chen CH
AD  - Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
FAU - Wu, Ying-Ta
AU  - Wu YT
AUID- ORCID: 0000-0003-0156-963X
AD  - Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
FAU - Hacker, Timothy A
AU  - Hacker TA
AD  - Cardiovascular Physiology Core Facility, Department of Medicine, University of 
      Wisconsin-Madison, Madison, WI 53705, USA.
FAU - Wu, Joseph C
AU  - Wu JC
AD  - Stanford Cardiovascular Institute, Stanford University School of Medicine, 
      Stanford, CA 94305, USA.
FAU - Kamp, Timothy J
AU  - Kamp TJ
AUID- ORCID: 0000-0003-2103-7876
AD  - Department of Medicine and Stem Cell and Regenerative Medicine Center, University 
      of Wisconsin-Madison, Madison, WI 53705, USA.
FAU - Hsieh, Patrick C H
AU  - Hsieh PCH
AUID- ORCID: 0000-0002-8910-3596
AD  - Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
AD  - Department of Medicine and Stem Cell and Regenerative Medicine Center, University 
      of Wisconsin-Madison, Madison, WI 53705, USA.
AD  - Institute of Clinical Medicine, National Taiwan University, Taipei 106, Taiwan.
LA  - eng
GR  - 109-2321-B-001-012/Ministry of Science and Technology/
PT  - Journal Article
DEP - 20220620
PL  - Switzerland
TA  - Pharmaceuticals (Basel)
JT  - Pharmaceuticals (Basel, Switzerland)
JID - 101238453
PMC - PMC9231250
OTO - NOTNLM
OT  - COVID-19
OT  - cardiomyocyte
OT  - drug screening
OT  - human leukocyte antigen
OT  - human-induced pluripotent stem cell
OT  - neuron
OT  - stem cell research
OT  - toxicity
COIS- The authors declare no conflict of interest.
EDAT- 2022/06/25 06:00
MHDA- 2022/06/25 06:01
PMCR- 2022/06/20
CRDT- 2022/06/24 01:37
PHST- 2022/05/30 00:00 [received]
PHST- 2022/06/15 00:00 [revised]
PHST- 2022/06/16 00:00 [accepted]
PHST- 2022/06/24 01:37 [entrez]
PHST- 2022/06/25 06:00 [pubmed]
PHST- 2022/06/25 06:01 [medline]
PHST- 2022/06/20 00:00 [pmc-release]
AID - ph15060765 [pii]
AID - pharmaceuticals-15-00765 [pii]
AID - 10.3390/ph15060765 [doi]
PST - epublish
SO  - Pharmaceuticals (Basel). 2022 Jun 20;15(6):765. doi: 10.3390/ph15060765.