Cardio- and Neurotoxicity of Selected Anti-COVID-19 Drugs
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-appro...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-06-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/15/6/765 |
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| author | Martin W. Nicholson Ching-Ying Huang Jyun-Yuan Wang Chien-Yu Ting Yu-Che Cheng Darien Z. H. Chan Yi-Chan Lee Ching-Chuan Hsu Yu-Hung Hsu Cindy M. C. Chang Marvin L. Hsieh Yuan-Yuan Cheng Yi-Ling Lin Chien-Hsiun Chen Ying-Ta Wu Timothy A. Hacker Joseph C. Wu Timothy J. Kamp Patrick C. H. Hsieh |
| author_facet | Martin W. Nicholson Ching-Ying Huang Jyun-Yuan Wang Chien-Yu Ting Yu-Che Cheng Darien Z. H. Chan Yi-Chan Lee Ching-Chuan Hsu Yu-Hung Hsu Cindy M. C. Chang Marvin L. Hsieh Yuan-Yuan Cheng Yi-Ling Lin Chien-Hsiun Chen Ying-Ta Wu Timothy A. Hacker Joseph C. Wu Timothy J. Kamp Patrick C. H. Hsieh |
| author_sort | Martin W. Nicholson |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T22:46:11Z |
| format | Article |
| id | doaj.art-281becb748f34355a75c8da991a28a2e |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T22:46:11Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-281becb748f34355a75c8da991a28a2e2023-11-23T18:28:20ZengMDPI AGPharmaceuticals1424-82472022-06-0115676510.3390/ph15060765Cardio- and Neurotoxicity of Selected Anti-COVID-19 DrugsMartin W. Nicholson0Ching-Ying Huang1Jyun-Yuan Wang2Chien-Yu Ting3Yu-Che Cheng4Darien Z. H. Chan5Yi-Chan Lee6Ching-Chuan Hsu7Yu-Hung Hsu8Cindy M. C. Chang9Marvin L. Hsieh10Yuan-Yuan Cheng11Yi-Ling Lin12Chien-Hsiun Chen13Ying-Ta Wu14Timothy A. Hacker15Joseph C. Wu16Timothy J. Kamp17Patrick C. H. Hsieh18Institute of Biomedical Sciences, Academia Sinica, Taipei 115, TaiwanInstitute of Biomedical Sciences, Academia Sinica, Taipei 115, TaiwanGenomics Research Center, Academia Sinica, Taipei 115, TaiwanInstitute of Biomedical Sciences, Academia Sinica, Taipei 115, TaiwanInstitute of Biomedical Sciences, Academia Sinica, Taipei 115, TaiwanInstitute of Biomedical Sciences, Academia Sinica, Taipei 115, TaiwanInstitute of Biomedical Sciences, Academia Sinica, Taipei 115, TaiwanInstitute of Biomedical Sciences, Academia Sinica, Taipei 115, TaiwanInstitute of Biomedical Sciences, Academia Sinica, Taipei 115, TaiwanCardiovascular Physiology Core Facility, Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USAInstitute of Biomedical Sciences, Academia Sinica, Taipei 115, TaiwanInstitute of Biomedical Sciences, Academia Sinica, Taipei 115, TaiwanInstitute of Biomedical Sciences, Academia Sinica, Taipei 115, TaiwanInstitute of Biomedical Sciences, Academia Sinica, Taipei 115, TaiwanGenomics Research Center, Academia Sinica, Taipei 115, TaiwanCardiovascular Physiology Core Facility, Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USAStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USADepartment of Medicine and Stem Cell and Regenerative Medicine Center, University of Wisconsin-Madison, Madison, WI 53705, USAInstitute of Biomedical Sciences, Academia Sinica, Taipei 115, TaiwanSince 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.https://www.mdpi.com/1424-8247/15/6/765stem cell researchcardiomyocyteneurondrug screeninghuman leukocyte antigenhuman-induced pluripotent stem cell |
| spellingShingle | Martin W. Nicholson Ching-Ying Huang Jyun-Yuan Wang Chien-Yu Ting Yu-Che Cheng Darien Z. H. Chan Yi-Chan Lee Ching-Chuan Hsu Yu-Hung Hsu Cindy M. C. Chang Marvin L. Hsieh Yuan-Yuan Cheng Yi-Ling Lin Chien-Hsiun Chen Ying-Ta Wu Timothy A. Hacker Joseph C. Wu Timothy J. Kamp Patrick C. H. Hsieh Cardio- and Neurotoxicity of Selected Anti-COVID-19 Drugs Pharmaceuticals stem cell research cardiomyocyte neuron drug screening human leukocyte antigen human-induced pluripotent stem cell |
| title | Cardio- and Neurotoxicity of Selected Anti-COVID-19 Drugs |
| title_full | Cardio- and Neurotoxicity of Selected Anti-COVID-19 Drugs |
| title_fullStr | Cardio- and Neurotoxicity of Selected Anti-COVID-19 Drugs |
| title_full_unstemmed | Cardio- and Neurotoxicity of Selected Anti-COVID-19 Drugs |
| title_short | Cardio- and Neurotoxicity of Selected Anti-COVID-19 Drugs |
| title_sort | cardio and neurotoxicity of selected anti covid 19 drugs |
| topic | stem cell research cardiomyocyte neuron drug screening human leukocyte antigen human-induced pluripotent stem cell |
| url | https://www.mdpi.com/1424-8247/15/6/765 |
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