Analgesics
Antiandrogens
Antihistamines
Azvudine
Bromhexine
Budesonide
Colchicine
Conv. Plasma
Curcumin
Famotidine
Favipiravir
Fluvoxamine
Hydroxychlor..
Ivermectin
Lifestyle
Melatonin
Metformin
Minerals
Molnupiravir
Monoclonals
Naso/orophar..
Nigella Sativa
Nitazoxanide
Paxlovid
Quercetin
Remdesivir
Thermotherapy
Vitamins
More

Other
Feedback
Home
Top
Abstract
All ivermectin studies
Meta analysis
 
Feedback
Home
next
study
previous
study
c19ivm.org COVID-19 treatment researchIvermectinIvermectin (more..)
Melatonin Meta
Metformin Meta
Antihistamines Meta
Azvudine Meta Molnupiravir Meta
Bromhexine Meta
Budesonide Meta
Colchicine Meta Nigella Sativa Meta
Conv. Plasma Meta Nitazoxanide Meta
Curcumin Meta Paxlovid Meta
Famotidine Meta Quercetin Meta
Favipiravir Meta Remdesivir Meta
Fluvoxamine Meta Thermotherapy Meta
Hydroxychlor.. Meta
Ivermectin Meta

All Studies   Meta Analysis    Recent:   

Genome-wide analyses reveal the detrimental impacts of SARS-CoV-2 viral gene Orf9c on human pluripotent stem cell-derived cardiomyocytes

Liu et al., Stem Cell Reports, doi:10.1016/j.stemcr.2022.01.014 (date from preprint)
Jan 2022  
  Post
  Facebook
Share
  Source   PDF   All Studies   Meta AnalysisMeta
Ivermectin for COVID-19
4th treatment shown to reduce risk in August 2020
 
*, now with p < 0.00000000001 from 104 studies, recognized in 23 countries.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,400+ studies for 79 treatments. c19ivm.org
In Vitro study showing that ivermectin and meclizine treatment may minimize SARS-CoV-2-induced cardiac damage by reducing Orf9c-induced apoptosis and dysfunction. Using human pluripotent stem cell-derived cardiomyocytes, authors show that the SARS-CoV-2 gene Orf9c may play a key role in the detrimental effects of the virus on cardiomyocytes by reducing ATP levels.
68 preclinical studies support the efficacy of ivermectin for COVID-19:
Ivermectin, better known for antiparasitic activity, is a broad spectrum antiviral with activity against many viruses including H7N766, Dengue32,67,68, HIV-168, Simian virus 4069, Zika32,70,71, West Nile71, Yellow Fever72,73, Japanese encephalitis72, Chikungunya73, Semliki Forest virus73, Human papillomavirus52, Epstein-Barr52, BK Polyomavirus74, and Sindbis virus73.
Ivermectin inhibits importin-α/β-dependent nuclear import of viral proteins66,68,69,75, shows spike-ACE2 disruption at 1nM with microfluidic diffusional sizing33, binds to glycan sites on the SARS-CoV-2 spike protein preventing interaction with blood and epithelial cells and inhibiting hemagglutination36,76, shows dose-dependent inhibition of wildtype and omicron variants31, exhibits dose-dependent inhibition of lung injury56,61, may inhibit SARS-CoV-2 via IMPase inhibition32, may inhibit SARS-CoV-2 induced formation of fibrin clots resistant to degradation5, inhibits SARS-CoV-2 3CLpro49, may inhibit SARS-CoV-2 RdRp activity24, may minimize viral myocarditis by inhibiting NF-κB/p65-mediated inflammation in macrophages55, may be beneficial for COVID-19 ARDS by blocking GSDMD and NET formation77, may inhibit SARS-CoV-2 by disrupting CD147 interaction78-81, shows protection against inflammation, cytokine storm, and mortality in an LPS mouse model sharing key pathological features of severe COVID-1954,82, may be beneficial in severe COVID-19 by binding IGF1 to inhibit the promotion of inflammation, fibrosis, and cell proliferation that leads to lung damage4, may minimize SARS-CoV-2 induced cardiac damage35,43, increases Bifidobacteria which play a key role in the immune system83, has immunomodulatory46 and anti-inflammatory65,84 properties, and has an extensive and very positive safety profile85.
Liu et al., 23 Jan 2022, peer-reviewed, 11 authors. Contact: lyang7@iu.edu (corresponding author).
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperIvermectinAll
SARS-CoV-2 Viral Genes Compromise Survival and Functions of Human Pluripotent Stem Cell-derived Cardiomyocytes via Reducing Cellular ATP Level
Juli Liu, Yucheng Zhang, Shiyong Wu, Lei Han, Cheng Wang, Sheng Liu, Ed Simpson, Ying Liu, Yue Wang, Weinian Shou, Yunlong Liu, Michael Rubart-Von Der Lohe, Jun Wan, Lei Yang
doi:10.1101/2022.01.20.477147
Cardiac manifestations are commonly observed in COVID-19 patients and prominently contributed to overall mortality. Human myocardium could be infected by SARS-CoV-2, and human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) are susceptible to SARS-CoV-2 infection. However, molecular mechanisms of SARS-CoV-2 gene-induced injury and dysfunction of human CMs remain elusive. Here, we find overexpression of three SARS-CoV-2 coding genes, Nsp6, Nsp8 and M, could globally compromise transcriptome of hPSC-CMs. Integrated transcriptomic analyses of hPSC-CMs infected by SARS-CoV-2 with hPSC-CMs of Nsp6, Nsp8 or M overexpression identified concordantly activated genes enriched into apoptosis and immune/inflammation responses, whereas reduced genes related to heart contraction and functions. Further, Nsp6, Nsp8 or M overexpression induce prominent apoptosis and electrical dysfunctions of hPSC-CMs. Global interactome analysis find Nsp6, Nsp8 and M all interact with ATPase subunits, leading to significantly reduced cellular ATP level of hPSC-CMs. Finally, we find two FDA-approved drugs, ivermectin and meclizine, could enhance the ATP level, and ameliorate cell death and dysfunctions of hPSC-CMs overexpressing Nsp6, Nsp8 or M. Overall, we uncover the global detrimental impacts of SARS-CoV-2 genes Nsp6, Nsp8 and M on the whole transcriptome and interactome of hPSC-CMs, define the crucial role of ATP level reduced by SARS-CoV-2 genes in CM death and functional abnormalities, and explore the potentially pharmaceutical approaches to ameliorate SARS-CoV-2 genes-induced CM injury and abnormalities.
Author contributions JL and LY initiated and designed studies. JL performed all experiments and data analyses. SW, LH, CW, ES, YW and YLL assisted in whole RNA-seq. YZ and JW assisted in bioinformatics. YL, WS and ML supported calcium handling and MEA experiments and data analyses. JL, JW, ML and LY wrote the manuscript. Declaration of interest The authors declare no competing interests. Supplementary Figure 1 Supplemental Information acquisition a minimum AGC of 2e3 and charge exclusion of 1, and ≥7 were used.
References
Bailey, Dmytrenko, Greenberg, SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 Myocarditis, J Am Coll Cardiol Basic Trans Science
Bailey, Dmytrenko, Greenberg, SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 Myocarditis, J Am Coll Cardiol Basic Transl Science
Banerjee, Blanco, Bruce, SARS-CoV-2 Disrupts Splicing, Translation, and Protein Trafficking to Suppress Host Defenses, Cell
Bers, Calcium cycling and signaling in cardiac myocytes, Annu Rev Physiol
Bers, Guo, Calcium signaling in cardiac ventricular myocytes, Ann N Y Acad Sci
Bojkova, Wagner, Shumliakivska, SARS-CoV-2 infects and induces cytotoxic effects in human cardiomyocytes, Cardiovasc Res
Brinton, Replication cycle and molecular biology of the West Nile virus, Viruses
Caly, Druce, Catton, Jans, Wagstaff, The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro, Antiviral Res
Clerkin, Fried, Raikhelkar, COVID-19 and Cardiovascular Disease, Circulation
Dhakal, Sweitzer, Indik, Acharya, William, SARS-CoV-2 Infection and Cardiovascular Disease: COVID-19 Heart, Heart Lung Circ
Dobin, STAR: ultrafast universal RNA-seq aligner, Bioinformatics, doi:10.1093/bioinformatics/bts635
Eguchi, Shimizu, Tsujimoto, Intracellular ATP levels determine cell death fate by apoptosis or necrosis, Cancer Res
Fearnley, Roderick, Bootman, Calcium signaling in cardiac myocytes, Cold Spring Harb Perspect Biol
Gohil, Sheth, Nilsson, Nutrient-sensitized screening for drugs that shift energy metabolism from mitochondrial respiration to glycolysis, Nat Biotechnol
Gordon, Jang, Bouhaddou, A SARS-CoV-2 protein interaction map reveals targets for drug repurposing, Nature
Guo, Fan, Chen, Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19), JAMA Cardiol
Hikmet, Mear, Edvinsson, Micke, Uhlen et al., The protein expression profile of ACE2 in human tissues, Mol Syst Biol
Hoffmann, Kleine-Weber, Schroeder, SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor, Cell
Huang, Wang, Li, Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China, Lancet
Knight, Kotecha, Razvi, COVID-19: Myocardial Injury in Survivors, Circulation
Lian, Directed cardiomyocyte differentiation from human pluripotent stem cells by modulating Wnt/beta-catenin signaling under fully defined conditions, Nat Protoc, doi:10.1038/nprot.2012.150
Lian, Zhang, Azarin, Directed cardiomyocyte differentiation from human pluripotent stem cells by modulating Wnt/beta-catenin signaling under fully defined conditions, Nat Protoc
Liao, Smyth, Shi, The R package Rsubread is easier, faster, cheaper and better for alignment and quantification of RNA sequencing reads, Nucleic Acids Res, doi:10.1093/nar/gkz114
Lin, High-purity enrichment of functional cardiovascular cells from human iPS cells, Cardiovasc Res, doi:10.1093/cvr/cvs185
Liu, Li, Lin, Sheng, Yang, HBL1 Is a Human Long Noncoding RNA that Modulates Cardiomyocyte Development from Pluripotent Stem Cells by Counteracting MIR1, Dev Cell
Liu, Liu, Gao, Genome-wide studies reveal the essential and opposite roles of ARID1A in controlling human cardiogenesis and neurogenesis from pluripotent stem cells, Genome Biol
Lu, Overexpression of microRNA-1 promotes cardiomyocyte commitment from human cardiovascular progenitors via suppressing WNT and FGF signaling pathways, J Mol Cell Cardiol, doi:10.1016/j.yjmcc.2013.07.019
Ludwig, Bergendahl, Levenstein, Yu, Probasco et al., Feeder-independent culture of human embryonic stem cells, Nat Methods
Ludwig, Derivation of human embryonic stem cells in defined conditions, Nat Biotechnol, doi:10.1038/nbt1177
Ludwig, Feeder-independent culture of human embryonic stem cells, Nat Methods, doi:10.1038/nmeth902
Ludwig, Levenstein, Jones, Derivation of human embryonic stem cells in defined conditions, Nat Biotechnol
Marchiano, Hsiang, Khanna, SARS-CoV-2 Infects Human Pluripotent Stem Cell-Derived Cardiomyocytes, Impairing Electrical and Mechanical Function, Stem Cell Reports
Medigeshi, Hirsch, Streblow, Nikolich-Zugich, Nelson, West Nile virus entry requires cholesterol-rich membrane microdomains and is independent of alphavbeta3 integrin, J Virol
Miyoshi, Oubrahim, Chock, Stadtman, Age-dependent cell death and the role of ATP in hydrogen peroxide-induced apoptosis and necrosis, Proc Natl Acad Sci U S A
Nagai, Satomi, Abiru, Antihypertrophic Effects of Small Molecules that Maintain Mitochondrial ATP Levels Under Hypoxia, EBioMedicine
Nishiga, Wang, Han, Lewis, Wu, COVID-19 and cardiovascular disease: from basic mechanisms to clinical perspectives, Nat Rev Cardiol
Peltier, Latham, Normalization of microRNA expression levels in quantitative RT-PCR assays: identification of suitable reference RNA targets in normal and cancerous human solid tissues, RNA, doi:10.1261/rna.939908
Perez-Bermejo, Kang, Rockwood, SARS-CoV-2 infection of human iPSC-derived cardiac cells predicts novel cytopathic features in hearts of COVID-19 patients, bioRxiv
Rajter, Sherman, Fatteh, Vogel, Sacks et al., Use of Ivermectin Is Associated With Lower Mortality in Hospitalized Patients With Coronavirus Disease, Chest
Robinson, Mccarthy, Smyth, edgeR: a Bioconductor package for differential expression analysis of digital gene expression data, Bioinformatics, doi:10.1093/bioinformatics/btp616
Shang, Wan, Luo, Cell entry mechanisms of SARS-CoV-2, Proc Natl Acad Sci U S A
Sharma, Garcia, Wang, Human iPSC-Derived Cardiomyocytes Are Susceptible to SARS-CoV-2 Infection, Cell Rep Med
Shi, Qin, Shen, Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China, JAMA Cardiol
Shi, Qin, Yang, Coronavirus Disease 2019 (COVID-19) and Cardiac Injury-Reply, JAMA Cardiol
Tatsumi, Shiraishi, Intracellular ATP is required for mitochondrial apoptotic pathways in isolated hypoxic rat cardiac myocytes, Cardiovasc Res
Tohyama, Hattori, Sano, Distinct metabolic flow enables large-scale purification of mouse and human pluripotent stem cell-derived cardiomyocytes, Cell Stem Cell
Tsujimoto, Apoptosis and necrosis: intracellular ATP level as a determinant for cell death modes, Cell Death Differ
Yang, Han, Nilsson-Payant, A Human Pluripotent Stem Cell-based Platform to Study SARS-CoV-2 Tropism and Model Virus Infection in Human Cells and Organoids, Cell Stem Cell
Yang, Human cardiovascular progenitor cells develop from a KDR+ embryonic-stem-cell-derived population, Nature, doi:10.1038/nature06894
Yang, Soonpaa, Adler, Human cardiovascular progenitor cells develop from a KDR+ embryonic-stem-cell-derived population, Nature
Zang, Castro, Mccune, TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes, Sci Immunol
Zhou, Yang, Wang, A pneumonia outbreak associated with a new coronavirus of probable bat origin, Nature
Zhu, Zhang, A Novel Coronavirus from Patients with Pneumonia in China, 2019, N Engl J Med
Zhuo, Gorgun, Englander, Augmentation of glycolytic metabolism by meclizine is indispensable for protection of dorsal root ganglion neurons from hypoxia-induced mitochondrial compromise, Free Radic Biol Med
{ 'indexed': {'date-parts': [[2023, 7, 6]], 'date-time': '2023-07-06T05:30:47Z', 'timestamp': 1688621447937}, 'reference-count': 45, 'publisher': 'Elsevier BV', 'issue': '3', 'license': [ { 'start': { 'date-parts': [[2022, 3, 1]], 'date-time': '2022-03-01T00:00:00Z', 'timestamp': 1646092800000}, 'content-version': 'tdm', 'delay-in-days': 0, 'URL': 'https://www.elsevier.com/tdm/userlicense/1.0/'}, { 'start': { 'date-parts': [[2022, 1, 18]], 'date-time': '2022-01-18T00:00:00Z', 'timestamp': 1642464000000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'http://creativecommons.org/licenses/by/4.0/'}], 'content-domain': { 'domain': ['cell.com', 'elsevier.com', 'sciencedirect.com'], 'crossmark-restriction': True}, 'published-print': {'date-parts': [[2022, 3]]}, 'DOI': '10.1016/j.stemcr.2022.01.014', 'type': 'journal-article', 'created': {'date-parts': [[2022, 2, 17]], 'date-time': '2022-02-17T15:33:09Z', 'timestamp': 1645111989000}, 'page': '522-537', 'update-policy': 'http://dx.doi.org/10.1016/elsevier_cm_policy', 'source': 'Crossref', 'is-referenced-by-count': 1, 'title': 'Genome-wide analyses reveal the detrimental impacts of SARS-CoV-2 viral gene Orf9c on human ' 'pluripotent stem cell-derived cardiomyocytes', 'prefix': '10.1016', 'volume': '17', 'author': [ {'given': 'Juli', 'family': 'Liu', 'sequence': 'first', 'affiliation': []}, {'given': 'Yucheng', 'family': 'Zhang', 'sequence': 'additional', 'affiliation': []}, {'given': 'Lei', 'family': 'Han', 'sequence': 'additional', 'affiliation': []}, {'given': 'Shuai', 'family': 'Guo', 'sequence': 'additional', 'affiliation': []}, {'given': 'Shiyong', 'family': 'Wu', 'sequence': 'additional', 'affiliation': []}, {'given': 'Emma Helen', 'family': 'Doud', 'sequence': 'additional', 'affiliation': []}, {'given': 'Cheng', 'family': 'Wang', 'sequence': 'additional', 'affiliation': []}, {'given': 'Hanying', 'family': 'Chen', 'sequence': 'additional', 'affiliation': []}, { 'given': 'Michael', 'family': 'Rubart-von der Lohe', 'sequence': 'additional', 'affiliation': []}, {'given': 'Jun', 'family': 'Wan', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-1479-2374', 'authenticated-orcid': False, 'given': 'Lei', 'family': 'Yang', 'sequence': 'additional', 'affiliation': []}], 'member': '78', 'reference': [ { 'key': '10.1016/j.stemcr.2022.01.014_bib1', 'doi-asserted-by': 'crossref', 'first-page': 'C57', 'DOI': '10.1152/ajpcell.00426.2020', 'article-title': 'Mitochondrial metabolic manipulation by SARS-CoV-2 in peripheral blood ' 'mononuclear cells of patients with COVID-19', 'volume': '320', 'author': 'Ajaz', 'year': '2021', 'journal-title': 'Am. J. Physiol. Cell Physiol.'}, { 'key': '10.1016/j.stemcr.2022.01.014_bib2', 'article-title': 'SARS-CoV-2 ORF9c is a membrane-associated protein that suppresses ' 'antiviral responses in cells', 'author': 'Andres', 'year': '2020', 'journal-title': 'bioRxiv'}, { 'key': '10.1016/j.stemcr.2022.01.014_bib3', 'doi-asserted-by': 'crossref', 'first-page': '331', 'DOI': '10.1016/j.jacbts.2021.01.002', 'article-title': 'SARS-CoV-2 infects human engineered heart tissues and models COVID-19 ' 'myocarditis', 'volume': '6', 'author': 'Bailey', 'year': '2021', 'journal-title': 'JACC Basic Transl. Sci.'}, { 'key': '10.1016/j.stemcr.2022.01.014_bib4', 'doi-asserted-by': 'crossref', 'first-page': '23', 'DOI': '10.1146/annurev.physiol.70.113006.100455', 'article-title': 'Calcium cycling and signaling in cardiac myocytes', 'volume': '70', 'author': 'Bers', 'year': '2008', 'journal-title': 'Annu. Rev. Physiol.'}, { 'key': '10.1016/j.stemcr.2022.01.014_bib5', 'doi-asserted-by': 'crossref', 'first-page': '86', 'DOI': '10.1196/annals.1341.008', 'article-title': 'Calcium signaling in cardiac ventricular myocytes', 'volume': '1047', 'author': 'Bers', 'year': '2005', 'journal-title': 'Ann. N. Y. Acad. Sci.'}, { 'key': '10.1016/j.stemcr.2022.01.014_bib6', 'doi-asserted-by': 'crossref', 'first-page': '2207', 'DOI': '10.1093/cvr/cvaa267', 'article-title': 'SARS-CoV-2 infects and induces cytotoxic effects in human ' 'cardiomyocytes', 'volume': '116', 'author': 'Bojkova', 'year': '2020', 'journal-title': 'Cardiovasc. Res.'}, { 'key': '10.1016/j.stemcr.2022.01.014_bib7', 'doi-asserted-by': 'crossref', 'first-page': '104787', 'DOI': '10.1016/j.antiviral.2020.104787', 'article-title': 'The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 ' 'in\xa0vitro', 'volume': '178', 'author': 'Caly', 'year': '2020', 'journal-title': 'Antivir. Res.'}, { 'key': '10.1016/j.stemcr.2022.01.014_bib8', 'doi-asserted-by': 'crossref', 'first-page': '808', 'DOI': '10.1038/nature09005', 'article-title': 'Patient-specific induced pluripotent stem-cell-derived models of ' 'LEOPARD syndrome', 'volume': '465', 'author': 'Carvajal-Vergara', 'year': '2010', 'journal-title': 'Nature'}, { 'key': '10.1016/j.stemcr.2022.01.014_bib9', 'doi-asserted-by': 'crossref', 'first-page': '829', 'DOI': '10.1016/j.kint.2020.03.005', 'article-title': 'Kidney disease is associated with in-hospital death of patients with ' 'COVID-19', 'volume': '97', 'author': 'Cheng', 'year': '2020', 'journal-title': 'Kidney Int.'}, { 'key': '10.1016/j.stemcr.2022.01.014_bib10', 'doi-asserted-by': 'crossref', 'first-page': '973', 'DOI': '10.1016/j.hlc.2020.05.101', 'article-title': 'SARS-CoV-2 infection and cardiovascular disease: COVID-19 heart', 'volume': '29', 'author': 'Dhakal', 'year': '2020', 'journal-title': 'Heart Lung Circ.'}, { 'key': '10.1016/j.stemcr.2022.01.014_bib11', 'first-page': '1835', 'article-title': 'Intracellular ATP levels determine cell death fate by apoptosis or ' 'necrosis', 'volume': '57', 'author': 'Eguchi', 'year': '1997', 'journal-title': 'Cancer Res.'}, { 'key': '10.1016/j.stemcr.2022.01.014_bib12', 'doi-asserted-by': 'crossref', 'first-page': 'a004242', 'DOI': '10.1101/cshperspect.a004242', 'article-title': 'Calcium signaling in cardiac myocytes', 'volume': '3', 'author': 'Fearnley', 'year': '2011', 'journal-title': 'Cold Spring Harb. Perspect. Biol.'}, { 'key': '10.1016/j.stemcr.2022.01.014_bib13', 'doi-asserted-by': 'crossref', 'first-page': '431', 'DOI': '10.1038/s41576-018-0008-z', 'article-title': 'Heterogeneity and specialized functions of translation machinery: from ' 'genes to organisms', 'volume': '19', 'author': 'Genuth', 'year': '2018', 'journal-title': 'Nat. Rev. Genet.'}, { 'key': '10.1016/j.stemcr.2022.01.014_bib14', 'doi-asserted-by': 'crossref', 'first-page': '249', 'DOI': '10.1038/nbt.1606', 'article-title': 'Nutrient-sensitized screening for drugs that shift energy metabolism ' 'from mitochondrial respiration to glycolysis', 'volume': '28', 'author': 'Gohil', 'year': '2010', 'journal-title': 'Nat. Biotechnol.'}, { 'key': '10.1016/j.stemcr.2022.01.014_bib15', 'doi-asserted-by': 'crossref', 'first-page': '459', 'DOI': '10.1038/s41586-020-2286-9', 'article-title': 'A SARS-CoV-2 protein interaction map reveals targets for drug ' 'repurposing', 'volume': '583', 'author': 'Gordon', 'year': '2020', 'journal-title': 'Nature'}, { 'key': '10.1016/j.stemcr.2022.01.014_bib16', 'doi-asserted-by': 'crossref', 'first-page': '811', 'DOI': '10.1001/jamacardio.2020.1017', 'article-title': 'Cardiovascular implications of fatal outcomes of patients with ' 'coronavirus disease 2019 (COVID-19)', 'volume': '5', 'author': 'Guo', 'year': '2020', 'journal-title': 'JAMA Cardiol.'}, { 'key': '10.1016/j.stemcr.2022.01.014_bib17', 'doi-asserted-by': 'crossref', 'first-page': 'e9610', 'DOI': '10.15252/msb.20209610', 'article-title': 'The protein expression profile of ACE2 in human tissues', 'volume': '16', 'author': 'Hikmet', 'year': '2020', 'journal-title': 'Mol. Syst. Biol.'}, { 'key': '10.1016/j.stemcr.2022.01.014_bib18', 'doi-asserted-by': 'crossref', 'first-page': '271', 'DOI': '10.1016/j.cell.2020.02.052', 'article-title': 'SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a ' 'clinically proven protease inhibitor', 'volume': '181', 'author': 'Hoffmann', 'year': '2020', 'journal-title': 'Cell'}, { 'key': '10.1016/j.stemcr.2022.01.014_bib19', 'doi-asserted-by': 'crossref', 'first-page': '497', 'DOI': '10.1016/S0140-6736(20)30183-5', 'article-title': 'Clinical features of patients infected with 2019 novel coronavirus in ' 'Wuhan, China', 'volume': '395', 'author': 'Huang', 'year': '2020', 'journal-title': 'Lancet'}, { 'key': '10.1016/j.stemcr.2022.01.014_bib20', 'doi-asserted-by': 'crossref', 'first-page': '141', 'DOI': '10.1016/j.bbabio.2004.05.007', 'article-title': '"Wages of fear": transient threefold decrease in intracellular ATP ' 'level imposes apoptosis', 'volume': '1658', 'author': 'Izyumov', 'year': '2004', 'journal-title': 'Biochim. Biophys. Acta'}, { 'key': '10.1016/j.stemcr.2022.01.014_bib21', 'doi-asserted-by': 'crossref', 'first-page': '1887', 'DOI': '10.1161/CIRCULATIONAHA.120.047969', 'article-title': 'The COVID-19 pandemic A massive threat for those living with ' 'cardiovascular disease among the poorest billion', 'volume': '142', 'author': 'Klassen', 'year': '2020', 'journal-title': 'Circulation'}, { 'key': '10.1016/j.stemcr.2022.01.014_bib22', 'doi-asserted-by': 'crossref', 'first-page': '508', 'DOI': '10.3390/cells8050508', 'article-title': 'Regulation of ribosomal proteins on viral infection', 'volume': '8', 'author': 'Li', 'year': '2019', 'journal-title': 'Cells'}, { 'key': '10.1016/j.stemcr.2022.01.014_bib23', 'doi-asserted-by': 'crossref', 'first-page': '162', 'DOI': '10.1038/nprot.2012.150', 'article-title': 'Directed cardiomyocyte differentiation from human pluripotent stem ' 'cells by modulating Wnt/beta-catenin signaling under fully defined ' 'conditions', 'volume': '8', 'author': 'Lian', 'year': '2013', 'journal-title': 'Nat. Protoc.'}, { 'key': '10.1016/j.stemcr.2022.01.014_bib24', 'doi-asserted-by': 'crossref', 'first-page': '327', 'DOI': '10.1093/cvr/cvs185', 'article-title': 'High-purity enrichment of functional cardiovascular cells from human ' 'iPS cells', 'volume': '95', 'author': 'Lin', 'year': '2012', 'journal-title': 'Cardiovasc. Res.'}, { 'key': '10.1016/j.stemcr.2022.01.014_bib25', 'doi-asserted-by': 'crossref', 'first-page': '1426', 'DOI': '10.1001/jama.2021.3071', 'article-title': 'Effect of ivermectin on time to resolution of symptoms among adults ' 'with mild COVID-19 A randomized clinical trial', 'volume': '325', 'author': 'Lopez-Medina', 'year': '2021', 'journal-title': 'JAMA'}, { 'key': '10.1016/j.stemcr.2022.01.014_bib26', 'doi-asserted-by': 'crossref', 'first-page': '637', 'DOI': '10.1038/nmeth902', 'article-title': 'Feeder-independent culture of human embryonic stem cells', 'volume': '3', 'author': 'Ludwig', 'year': '2006', 'journal-title': 'Nat. Methods'}, { 'key': '10.1016/j.stemcr.2022.01.014_bib27', 'doi-asserted-by': 'crossref', 'first-page': '185', 'DOI': '10.1038/nbt1177', 'article-title': 'Derivation of human embryonic stem cells in defined conditions', 'volume': '24', 'author': 'Ludwig', 'year': '2006', 'journal-title': 'Nat. Biotechnol.'}, { 'key': '10.1016/j.stemcr.2022.01.014_bib28', 'doi-asserted-by': 'crossref', 'first-page': '478', 'DOI': '10.1016/j.stemcr.2021.02.008', 'article-title': 'SARS-CoV-2 infects human pluripotent stem cell-derived cardiomyocytes, ' 'impairing electrical and mechanical function', 'volume': '16', 'author': 'Marchiano', 'year': '2021', 'journal-title': 'Stem Cell Rep.'}, { 'key': '10.1016/j.stemcr.2022.01.014_bib29', 'doi-asserted-by': 'crossref', 'first-page': '1727', 'DOI': '10.1073/pnas.0510346103', 'article-title': 'Age-dependent cell death and the role of ATP in hydrogen ' 'peroxide-induced apoptosis and necrosis', 'volume': '103', 'author': 'Miyoshi', 'year': '2006', 'journal-title': 'Proc. Natl. Acad. Sci. U S A'}, { 'key': '10.1016/j.stemcr.2022.01.014_bib30', 'doi-asserted-by': 'crossref', 'first-page': '147', 'DOI': '10.1016/j.ebiom.2017.09.022', 'article-title': 'Antihypertrophic effects of small molecules that maintain mitochondrial ' 'ATP levels under hypoxia', 'volume': '24', 'author': 'Nagai', 'year': '2017', 'journal-title': 'Ebiomedicine'}, { 'key': '10.1016/j.stemcr.2022.01.014_bib31', 'doi-asserted-by': 'crossref', 'first-page': '543', 'DOI': '10.1038/s41569-020-0413-9', 'article-title': 'COVID-19 and cardiovascular disease: from basic mechanisms to clinical ' 'perspectives', 'volume': '17', 'author': 'Nishiga', 'year': '2020', 'journal-title': 'Nat. Rev. Cardiol.'}, { 'key': '10.1016/j.stemcr.2022.01.014_bib32', 'first-page': 'eabf7872', 'article-title': 'SARS-CoV-2 infection of human iPSC-derived cardiac cells predicts novel ' 'cytopathic features in hearts of COVID-19 patients', 'volume': '590', 'author': 'Perez-Bermejo', 'year': '2020', 'journal-title': 'Sci. Transl. Med.'}, { 'key': '10.1016/j.stemcr.2022.01.014_bib33', 'doi-asserted-by': 'crossref', 'first-page': '100052', 'DOI': '10.1016/j.xcrm.2020.100052', 'article-title': 'Human iPSC-derived cardiomyocytes are susceptible to SARS-CoV-2 ' 'infection', 'volume': '1', 'author': 'Sharma', 'year': '2020', 'journal-title': 'Cell Rep. Med.'}, { 'key': '10.1016/j.stemcr.2022.01.014_bib34', 'doi-asserted-by': 'crossref', 'first-page': '802', 'DOI': '10.1001/jamacardio.2020.0950', 'article-title': 'Association of cardiac injury with mortality in hospitalized patients ' 'with COVID-19 in Wuhan, China', 'volume': '5', 'author': 'Shi', 'year': '2020', 'journal-title': 'JAMA Cardiol.'}, { 'key': '10.1016/j.stemcr.2022.01.014_bib35', 'doi-asserted-by': 'crossref', 'first-page': '802', 'DOI': '10.1001/jamacardio.2020.0950', 'article-title': 'Coronavirus disease 2019 (COVID-19) and cardiac injury-reply', 'volume': '7', 'author': 'Shi', 'year': '2020', 'journal-title': 'JAMA Cardiol.'}, { 'key': '10.1016/j.stemcr.2022.01.014_bib36', 'doi-asserted-by': 'crossref', 'first-page': 'H1637', 'DOI': '10.1152/ajpheart.2001.281.4.H1637', 'article-title': 'Important role of energy-dependent mitochondrial pathways in cultured ' 'rat cardiac myocyte apoptosis', 'volume': '281', 'author': 'Shiraishi', 'year': '2001', 'journal-title': 'Am. J. Physiol. Heart Circ. Physiol.'}, { 'key': '10.1016/j.stemcr.2022.01.014_bib37', 'doi-asserted-by': 'crossref', 'first-page': '473', 'DOI': '10.1007/s10495-006-5881-9', 'article-title': 'Bioenergetic aspects of apoptosis, necrosis and mitoptosis', 'volume': '11', 'author': 'Skulachev', 'year': '2006', 'journal-title': 'Apoptosis'}, { 'key': '10.1016/j.stemcr.2022.01.014_bib38', 'doi-asserted-by': 'crossref', 'first-page': '428', 'DOI': '10.1016/S0008-6363(03)00391-2', 'article-title': 'Intracellular ATP is required for mitochondrial apoptotic pathways in ' 'isolated hypoxic rat cardiac myocytes', 'volume': '59', 'author': 'Tatsumi', 'year': '2003', 'journal-title': 'Cardiovasc. Res.'}, { 'key': '10.1016/j.stemcr.2022.01.014_bib39', 'doi-asserted-by': 'crossref', 'first-page': '127', 'DOI': '10.1016/j.stem.2012.09.013', 'article-title': 'Distinct metabolic flow enables large-scale purification of mouse and ' 'human pluripotent stem cell-derived cardiomyocytes', 'volume': '12', 'author': 'Tohyama', 'year': '2013', 'journal-title': 'Cell Stem Cell'}, { 'key': '10.1016/j.stemcr.2022.01.014_bib40', 'doi-asserted-by': 'crossref', 'first-page': '429', 'DOI': '10.1038/sj.cdd.4400262', 'article-title': 'Apoptosis and necrosis: intracellular ATP level as a determinant for ' 'cell death modes', 'volume': '4', 'author': 'Tsujimoto', 'year': '1997', 'journal-title': 'Cell Death Differ.'}, { 'key': '10.1016/j.stemcr.2022.01.014_bib41', 'doi-asserted-by': 'crossref', 'first-page': '125', 'DOI': '10.1016/j.stem.2020.06.015', 'article-title': 'A human pluripotent stem cell-based platform to study SARS-CoV-2 ' 'tropism and model virus infection in human cells and organoids', 'volume': '27', 'author': 'Yang', 'year': '2020', 'journal-title': 'Cell Stem Cell'}, { 'key': '10.1016/j.stemcr.2022.01.014_bib42', 'doi-asserted-by': 'crossref', 'first-page': '524', 'DOI': '10.1038/nature06894', 'article-title': 'Human cardiovascular progenitor cells develop from a KDR+ ' 'embryonic-stem-cell-derived population', 'volume': '453', 'author': 'Yang', 'year': '2008', 'journal-title': 'Nature'}, { 'key': '10.1016/j.stemcr.2022.01.014_bib43', 'doi-asserted-by': 'crossref', 'first-page': 'eabc3582', 'DOI': '10.1126/sciimmunol.abc3582', 'article-title': 'TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small ' 'intestinal enterocytes', 'volume': '47', 'author': 'Zang', 'year': '2020', 'journal-title': 'Sci. Immunol.'}, { 'key': '10.1016/j.stemcr.2022.01.014_bib44', 'doi-asserted-by': 'crossref', 'first-page': '727', 'DOI': '10.1056/NEJMoa2001017', 'article-title': 'A novel coronavirus from patients with pneumonia in China, 2019', 'volume': '382', 'author': 'Zhu', 'year': '2020', 'journal-title': 'N.\xa0Engl. J. Med.'}, { 'key': '10.1016/j.stemcr.2022.01.014_bib45', 'doi-asserted-by': 'crossref', 'first-page': '20', 'DOI': '10.1016/j.freeradbiomed.2016.07.022', 'article-title': 'Augmentation of glycolytic metabolism by meclizine is indispensable for ' 'protection of dorsal root ganglion neurons from hypoxia-induced ' 'mitochondrial compromise', 'volume': '99', 'author': 'Zhuo', 'year': '2016', 'journal-title': 'Free Radic. Biol. Med.'}], 'container-title': 'Stem Cell Reports', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://api.elsevier.com/content/article/PII:S2213671122000583?httpAccept=text/xml', 'content-type': 'text/xml', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://api.elsevier.com/content/article/PII:S2213671122000583?httpAccept=text/plain', 'content-type': 'text/plain', 'content-version': 'vor', 'intended-application': 'text-mining'}], 'deposited': { 'date-parts': [[2022, 5, 30]], 'date-time': '2022-05-30T18:24:34Z', 'timestamp': 1653935074000}, 'score': 1, 'resource': {'primary': {'URL': 'https://linkinghub.elsevier.com/retrieve/pii/S2213671122000583'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2022, 3]]}, 'references-count': 45, 'journal-issue': {'issue': '3', 'published-print': {'date-parts': [[2022, 3]]}}, 'alternative-id': ['S2213671122000583'], 'URL': 'http://dx.doi.org/10.1016/j.stemcr.2022.01.014', 'relation': {}, 'ISSN': ['2213-6711'], 'subject': ['Cell Biology', 'Developmental Biology', 'Genetics', 'Biochemistry'], 'container-title-short': 'Stem Cell Reports', 'published': {'date-parts': [[2022, 3]]}, 'assertion': [ {'value': 'Elsevier', 'name': 'publisher', 'label': 'This article is maintained by'}, { 'value': 'Genome-wide analyses reveal the detrimental impacts of SARS-CoV-2 viral gene ' 'Orf9c on human pluripotent stem cell-derived cardiomyocytes', 'name': 'articletitle', 'label': 'Article Title'}, {'value': 'Stem Cell Reports', 'name': 'journaltitle', 'label': 'Journal Title'}, { 'value': 'https://doi.org/10.1016/j.stemcr.2022.01.014', 'name': 'articlelink', 'label': 'CrossRef DOI link to publisher maintained version'}, {'value': 'article', 'name': 'content_type', 'label': 'Content Type'}, {'value': '© 2022 The Author(s).', 'name': 'copyright', 'label': 'Copyright'}]}
Loading..
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
  or use drag and drop   
Submit