Evidence map›Paper›PMID 37315523›Full record

ArticleStem cell reports2023

Parallel use of human stem cell lung and heart models provide insights for SARS-CoV-2 treatment.

Rajeev Rudraraju, Matthew J Gartner, Jessica A Neil, Elizabeth S Stout, Joseph Chen, Elise J Needham, Michael See, Charley Mackenzie-Kludas, Leo Yi Yang Lee, Mingyang Wang and 18 more

Open access · goldAbstract read
In one paragraph

Article in Stem cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
2.3field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 12 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

28 authors at 6 institutions in 1 country.

Rajeev RudrarajuThe Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia.
Matthew J GartnerThe Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia.
Jessica A NeilThe Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia.
Elizabeth S StoutThe Novo Nordisk Foundation Centre for Stem Cell Medicine (reNEW), Murdoch Children's Research Institute, Melbourne, VIC, Australia.
Joseph ChenDepartment of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia; Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Clayton, VIC, Australia; Australian Regenerative Medicine Institute, Monash University, Clayton, VIC, Australia.
Elise J NeedhamCharles Perkins Centre and School of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Camperdown, NSW, Australia.
Michael SeeThe Novo Nordisk Foundation Centre for Stem Cell Medicine (reNEW), Murdoch Children's Research Institute, Melbourne, VIC, Australia; Monash Bioinformatics Platform, Monash University, Clayton, VIC, Australia.
Charley Mackenzie-KludasThe Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia.
Leo Yi Yang LeeThe Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia.
Mingyang WangThe Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia.
Hayley PointerThe Novo Nordisk Foundation Centre for Stem Cell Medicine (reNEW), Murdoch Children's Research Institute, Melbourne, VIC, Australia.
Kathy KaravendzasThe Novo Nordisk Foundation Centre for Stem Cell Medicine (reNEW), Murdoch Children's Research Institute, Melbourne, VIC, Australia.
Dad Abu-BonsrahThe Novo Nordisk Foundation Centre for Stem Cell Medicine (reNEW), Murdoch Children's Research Institute, Melbourne, VIC, Australia.
Damien DrewInfection and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
Yu Bo Yang SunDepartment of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia; Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Clayton, VIC, Australia; Australian Regenerative Medicine Institute, Monash University, Clayton, VIC, Australia.
Jia Ping TanDepartment of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia; Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Clayton, VIC, Australia; Australian Regenerative Medicine Institute, Monash University, Clayton, VIC, Australia.
Guizhi SunDepartment of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia; Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Clayton, VIC, Australia; Australian Regenerative Medicine Institute, Monash University, Clayton, VIC, Australia.
Adrian SalavatyAustralian Regenerative Medicine Institute, Monash University, Clayton, VIC, Australia; EMBL Australia, Monash University, Clayton, VIC, Australia.
Natalie CharitakisThe Novo Nordisk Foundation Centre for Stem Cell Medicine (reNEW), Murdoch Children's Research Institute, Melbourne, VIC, Australia; Department of Pediatrics, The Royal Children's Hospital, University of Melbourne Parkville, VIC, Australia.
Hieu T NimThe Novo Nordisk Foundation Centre for Stem Cell Medicine (reNEW), Murdoch Children's Research Institute, Melbourne, VIC, Australia; Australian Regenerative Medicine Institute, Monash University, Clayton, VIC, Australia; Department of Pediatrics, The Royal Children's Hospital, University of Melbourne Parkville, VIC, Australia.
Peter D CurrieAustralian Regenerative Medicine Institute, Monash University, Clayton, VIC, Australia; EMBL Australia, Monash University, Clayton, VIC, Australia.
Wai-Hong ThamInfection and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, VIC, Australia.
Enzo PorrelloThe Novo Nordisk Foundation Centre for Stem Cell Medicine (reNEW), Murdoch Children's Research Institute, Melbourne, VIC, Australia; Melbourne Centre for Cardiovascular Genomics and Regenerative Medicine, The Royal Children's Hospital, Melbourne, VIC, Australia; Department of Anatomy and Physiology, School of Biomedical Sciences, The University of Melbourne, Parkville, VIC, Australia. Electronic address: enzo.porrello@mcri.edu.au.
Jose M PoloDepartment of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia; Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Clayton, VIC, Australia; Australian Regenerative Medicine Institute, Monash University, Clayton, VIC, Australia. Electronic address: jose.polo@monash.edu.
Sean J HumphreyCharles Perkins Centre and School of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Camperdown, NSW, Australia. Electronic address: sean.humphrey@mcri.edu.au.
Mirana RamialisonThe Novo Nordisk Foundation Centre for Stem Cell Medicine (reNEW), Murdoch Children's Research Institute, Melbourne, VIC, Australia; Australian Regenerative Medicine Institute, Monash University, Clayton, VIC, Australia; Department of Pediatrics, The Royal Children's Hospital, University of Melbourne Parkville, VIC, Australia. Electronic address: mirana.ramialison@mcri.edu.au.
David A ElliottThe Novo Nordisk Foundation Centre for Stem Cell Medicine (reNEW), Murdoch Children's Research Institute, Melbourne, VIC, Australia; Australian Regenerative Medicine Institute, Monash University, Clayton, VIC, Australia; Department of Pediatrics, The Royal Children's Hospital, University of Melbourne Parkville, VIC, Australia. Electronic address: david.elliott@mcri.edu.au.
Kanta SubbaraoThe Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia; The WHO Collaborating Centre for Reference and Research on Influenza, The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia. Electronic address: kanta.subbarao@influenzacentre.org.
The University of Melbourne · AUAustralian Regenerative Medicine Institute · AUMurdoch Children's Research Institute · AURoyal Children's Hospital · AUThe University of Sydney · AUWalter and Eliza Hall Institute of Medical Research · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily infects the respiratory tract, but pulmonary and cardiac complications occur in severe coronavirus disease 2019 (COVID-19). To elucidate molecular mechanisms in the lung and heart, we conducted paired experiments in human stem cell-derived lung alveolar type II (AT2) epithelial cell and cardiac cultures infected with SARS-CoV-2. With CRISPR-Cas9-mediated knockout of ACE2, we demonstrated that angiotensin-converting enzyme 2 (ACE2) was essential for SARS-CoV-2 infection of both cell types but that further processing in lung cells required TMPRSS2, while cardiac cells required the endosomal pathway. Host responses were significantly different; transcriptome profiling and phosphoproteomics responses depended strongly on the cell type. We identified several antiviral compounds with distinct antiviral and toxicity profiles in lung AT2 and cardiac cells, highlighting the importance of using several relevant cell types for evaluation of antiviral drugs. Our data provide new insights into rational drug combinations for effective treatment of a virus that affects multiple organ systems.

Indexed as

COVID-19SARS-CoV-2Angiotensin-Converting Enzyme 2Antiviral AgentsHumansLungStem CellsAngiotensin-Converting Enzyme 2Antiviral Agentsantiviral drugsCOVID-19human stem cell-derived lung and heart modelsSARS-CoV-2

Identifiers

PMID37315523
PMCPMC10262339
OpenAlexW4380633032

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.