Evidence map›Paper›PMID 34731648›Full record

ArticleCell reports2021

An airway organoid-based screen identifies a role for the HIF1α-glycolysis axis in SARS-CoV-2 infection.

Xiaohua Duan, Xuming Tang, Manoj S Nair, Tuo Zhang, Yunping Qiu, Wei Zhang, Pengfei Wang, Yaoxing Huang, Jenny Xiang, Hui Wang and 4 more

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
3.7field-weighted citation impact, top 5% 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

48 citing papers in PubMed, 64 citations in OpenAlex.

  1. Review
  2. Host metabolic responses to SARS-CoV-2 and influenza viruses: parallels and contrasts.Metabolomics : Official journal of the Metabolomic Society · 2026
    Review
  3. Microbial production of xanthohumol driven by synthetic biology approaches.World journal of microbiology & biotechnology · 2026
    Review
  4. Review
  5. Article
  6. Review
  7. Review
  8. Article
  9. Emerging microbes & infections · 2025
    Article
  10. Review
  11. Article
  12. Review
  13. Review
  14. Organoids: physiologically relevantJournal of virology · 2025
    Review
  15. Review
  16. Article
  17. Perturbation ofJournal of virology · 2025
    Article
  18. Review
  19. Article
  20. Mitochondrial antioxidants abate SARS-COV-2 pathology in mice.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 4 institutions in 2 countries.

Xiaohua DuanDepartment of Surgery, Weill Cornell Medicine, 1300 York Ave., New York, NY 10065, USA; State Key Laboratory of Oncogenes and Related Genes, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Xuming TangDepartment of Surgery, Weill Cornell Medicine, 1300 York Ave., New York, NY 10065, USA.
Manoj S NairAaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.
Tuo ZhangGenomics Resources Core Facility, Weill Cornell Medicine, New York, NY 10065, USA.
Yunping QiuDepartment of Medicine, Fleischer Institute for Diabetes and Metabolism, Albert Einstein College of Medicine, Bronx, NY, USA.
Wei ZhangGenomics Resources Core Facility, Weill Cornell Medicine, New York, NY 10065, USA.
Pengfei WangAaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.
Yaoxing HuangAaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.
Jenny XiangGenomics Resources Core Facility, Weill Cornell Medicine, New York, NY 10065, USA.
Hui WangState Key Laboratory of Oncogenes and Related Genes, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: huiwang@shsmu.edu.cn.
Robert E SchwartzDivision of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, 1300 York Ave., New York, NY 10065, USA; Department of Physiology, Biophysics and Systems Biology, Weill Cornell Medicine, 1300 York Ave., New York, NY 10065, USA. Electronic address: res2025@med.cornell.edu.
David D HoAaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA. Electronic address: dh2994@cumc.columbia.edu.
Todd EvansDepartment of Surgery, Weill Cornell Medicine, 1300 York Ave., New York, NY 10065, USA. Electronic address: tre2003@med.cornell.edu.
Shuibing ChenDepartment of Surgery, Weill Cornell Medicine, 1300 York Ave., New York, NY 10065, USA. Electronic address: shc2034@med.cornell.edu.
Cornell University · USAaron Diamond AIDS Research Center · USShanghai Jiao Tong University · CNAlbert Einstein College of Medicine · US

Funding

Stable Isotope and Metabolomics CoreP60DK020541 · NIDDK · YESHIVA UNIVERSITY · PI PESSIN, JEFFREY E. · 1986 to 2014
$29.8M
Genetic Viral and Host Adaptations to Breach Species Barriers of HCVR01AI107301 · NIAID · PRINCETON UNIVERSITY · PI Thomas Pietschmann, Alexander Ploss · 2013 to 2026
$6.0M
Optimization of the engineered 3D hepatic microenvironment enhances pluripotent stem cell derived hepatocyteR01DK121072 · NIDDK · WEILL MEDICAL COLL OF CORNELL UNIV · PI SCHWARTZ, ROBERT E · 2020 to 2024
$2.6M
Metallothionein 1E as a Central Regulator of Human Pancreatic Beta Cell Function and SurvivalR01DK119667 · NIDDK · WEILL MEDICAL COLL OF CORNELL UNIV · PI CHEN, SHUIBING · 2019 to 2022
$2.5M
Discovery of T1DM Associated Functional Variants in Human Pancreatic Beta Cell Development and SurvivalDP3DK111907 · NIDDK · WEILL MEDICAL COLL OF CORNELL UNIV · PI CHEN, SHUIBING · 2016 to 2016
$2.0M
Modeling Hepatoblastoma using pluripotent stem cell derived hepatocyte-like cellsR01CA234614 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI SCHWARTZ, ROBERT E · 2019 to 2023
$1.9M
A High Content Chemical Screen to Identify the Drug Candidates Promoting Human Beta Cell ProliferationR01DK124463 · NIDDK · WEILL MEDICAL COLL OF CORNELL UNIV · PI CHEN, SHUIBING · 2020 to 2023
$1.7M
A High Throughput Screening to Identify Compounds Rescuing Human Pancreatic Beta Cell Function in Diabetic ConditionsR01DK116075 · NIDDK · WEILL MEDICAL COLL OF CORNELL UNIV · PI CHEN, SHUIBING · 2018 to 2020
$1.3M
Identification of Hepatitis B Virus permissiveness factorsR03DK117252 · NIDDK · WEILL MEDICAL COLL OF CORNELL UNIV · PI SCHWARTZ, ROBERT E · 2018 to 2019
$254k
NCI NIH HHS R01 CA234614NIAID NIH HHS R01 AI107301NIDDK NIH HHS DP3 DK111907NIDDK NIH HHS P60 DK020541NIDDK NIH HHS R01 DK116075NIDDK NIH HHS R01 DK119667NIDDK NIH HHS R01 DK121072NIDDK NIH HHS R01 DK124463NIDDK NIH HHS R03 DK117252
6 · The paper itself

Abstract

It is urgent to develop disease models to dissect mechanisms regulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we derive airway organoids from human pluripotent stem cells (hPSC-AOs). The hPSC-AOs, particularly ciliated-like cells, are permissive to SARS-CoV-2 infection. Using this platform, we perform a high content screen and identify GW6471, which blocks SARS-CoV-2 infection. GW6471 can also block infection of the B.1.351 SARS-CoV-2 variant. RNA sequencing (RNA-seq) analysis suggests that GW6471 blocks SARS-CoV-2 infection at least in part by inhibiting hypoxia inducible factor 1 subunit alpha (HIF1α), which is further validated by chemical inhibitor and genetic perturbation targeting HIF1α. Metabolic profiling identifies decreased rates of glycolysis upon GW6471 treatment, consistent with transcriptome profiling. Finally, xanthohumol, 5-(tetradecyloxy)-2-furoic acid, and ND-646, three compounds that suppress fatty acid biosynthesis, also block SARS-CoV-2 infection. Together, a high content screen coupled with transcriptome and metabolic profiling reveals a key role of the HIF1α-glycolysis axis in mediating SARS-CoV-2 infection of human airway epithelium.

Indexed as

AnimalsCell LineChlorocebus aethiopsCOVID-19Epithelial CellsGlycolysisHEK293 CellsHumansHypoxia-Inducible Factor 1, alpha SubunitLungOrganoidsPluripotent Stem CellsSARS-CoV-2TranscriptomeVero CellsHIF1A protein, humanHypoxia-Inducible Factor 1, alpha Subunitairway organoidfatty acid synthesisGW4671high content drug screenhypoxia-inducible factor 1-alphaSARS-CoV-2

Identifiers

PMID34731648
PMCPMC8516798
OpenAlexW3201950936

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.