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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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Autores principales: Nicholson, Martin W., Huang, Ching-Ying, Wang, Jyun-Yuan, Ting, Chien-Yu, Cheng, Yu-Che, Chan, Darien Z. H., Lee, Yi-Chan, Hsu, Ching-Chuan, Hsu, Yu-Hung, Chang, Cindy M. C., Hsieh, Marvin L., Cheng, Yuan-Yuan, Lin, Yi-Ling, Chen, Chien-Hsiun, Wu, Ying-Ta, Hacker, Timothy A., Wu, Joseph C., Kamp, Timothy J., Hsieh, Patrick C. H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9231250/
https://www.ncbi.nlm.nih.gov/pubmed/35745684
http://dx.doi.org/10.3390/ph15060765
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author Nicholson, Martin W.
Huang, Ching-Ying
Wang, Jyun-Yuan
Ting, Chien-Yu
Cheng, Yu-Che
Chan, Darien Z. H.
Lee, Yi-Chan
Hsu, Ching-Chuan
Hsu, Yu-Hung
Chang, Cindy M. C.
Hsieh, Marvin L.
Cheng, Yuan-Yuan
Lin, Yi-Ling
Chen, Chien-Hsiun
Wu, Ying-Ta
Hacker, Timothy A.
Wu, Joseph C.
Kamp, Timothy J.
Hsieh, Patrick C. H.
author_facet Nicholson, Martin W.
Huang, Ching-Ying
Wang, Jyun-Yuan
Ting, Chien-Yu
Cheng, Yu-Che
Chan, Darien Z. H.
Lee, Yi-Chan
Hsu, Ching-Chuan
Hsu, Yu-Hung
Chang, Cindy M. C.
Hsieh, Marvin L.
Cheng, Yuan-Yuan
Lin, Yi-Ling
Chen, Chien-Hsiun
Wu, Ying-Ta
Hacker, Timothy A.
Wu, Joseph C.
Kamp, Timothy J.
Hsieh, Patrick C. H.
author_sort Nicholson, Martin W.
collection PubMed
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.
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spelling pubmed-92312502022-06-25 Cardio- and Neurotoxicity of Selected Anti-COVID-19 Drugs Nicholson, Martin W. Huang, Ching-Ying Wang, Jyun-Yuan Ting, Chien-Yu Cheng, Yu-Che Chan, Darien Z. H. Lee, Yi-Chan Hsu, Ching-Chuan Hsu, Yu-Hung Chang, Cindy M. C. Hsieh, Marvin L. Cheng, Yuan-Yuan Lin, Yi-Ling Chen, Chien-Hsiun Wu, Ying-Ta Hacker, Timothy A. Wu, Joseph C. Kamp, Timothy J. Hsieh, Patrick C. H. Pharmaceuticals (Basel) Brief Report 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. MDPI 2022-06-20 /pmc/articles/PMC9231250/ /pubmed/35745684 http://dx.doi.org/10.3390/ph15060765 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Brief Report
Nicholson, Martin W.
Huang, Ching-Ying
Wang, Jyun-Yuan
Ting, Chien-Yu
Cheng, Yu-Che
Chan, Darien Z. H.
Lee, Yi-Chan
Hsu, Ching-Chuan
Hsu, Yu-Hung
Chang, Cindy M. C.
Hsieh, Marvin L.
Cheng, Yuan-Yuan
Lin, Yi-Ling
Chen, Chien-Hsiun
Wu, Ying-Ta
Hacker, Timothy A.
Wu, Joseph C.
Kamp, Timothy J.
Hsieh, Patrick C. H.
Cardio- and Neurotoxicity of Selected Anti-COVID-19 Drugs
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 Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9231250/
https://www.ncbi.nlm.nih.gov/pubmed/35745684
http://dx.doi.org/10.3390/ph15060765
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