Evidence map›Paper›PMID 33941899›Full record

ArticleNature biomedical engineering2021

A human-airway-on-a-chip for the rapid identification of candidate antiviral therapeutics and prophylactics.

Longlong Si, Haiqing Bai, Melissa Rodas, Wuji Cao, Crystal Yuri Oh, Amanda Jiang, Rasmus Moller, Daisy Hoagland, Kohei Oishi, Shu Horiuchi and 28 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature biomedical engineering, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 234 papers.

0numbers the graph read from it
0cells of the map it votes in
234citing papers in PubMed
27.2field-weighted citation impact, top 1% 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

234 citing papers in PubMed, 419 citations in OpenAlex.

  1. Review
  2. Review
  3. Leveraging Microphysiological Systems to Facilitate Neutrophil-Based Cancer Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  4. Review
  5. Angiogenesis in Lung Regeneration and Aging.Arteriosclerosis, thrombosis, and vascular biology · 2026
    Review
  6. Article
  7. Review
  8. Review
  9. Review
  10. Review
  11. Article
  12. Review
  13. Review
  14. Review
  15. Review
  16. A human airway-on-a-chip microphysiological system for modeling chlorine gas toxicity.Toxicological sciences : an official journal of the Society of Toxicology · 2026
    Article
  17. Review
  18. Review
  19. Article
  20. Article

174 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

38 authors at 6 institutions in 2 countries.

Longlong Si *Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.ORCID http://orcid.org/0000-0002-0504-1659
Haiqing Bai *Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
Melissa RodasWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
Wuji CaoWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
Crystal Yuri OhWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
Amanda JiangWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
Rasmus MollerDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0002-8452-0761
Daisy HoaglandDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Kohei OishiDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Shu HoriuchiDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Skyler UhlDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Daniel Blanco-MeloDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Randy A AlbrechtDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0003-4008-503X
Wen-Chun LiuDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Tristan JordanDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Benjamin E Nilsson-PayantDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0003-2661-7837
Ilona GolynkerDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Justin FrereDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0002-7514-8873
James LogueDepartment of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-7410-9741
Robert HauptDepartment of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.
Marisa McGrathDepartment of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-7451-4958
Stuart WestonDepartment of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.
Tian ZhangDepartment of Cell Biology, Harvard Medical School, Boston, MA, USA.
Roberto PlebaniWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
Mercy SoongWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
Atiq NuraniWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
Seong Min KimWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
Danni Y ZhuWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
Kambez H BenamWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
Girija GoyalWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
Sarah E GilpinWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
Rachelle Prantil-BaunWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
Steven P GygiDepartment of Cell Biology, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-7626-0034
Rani K PowersWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
Kenneth E CarlsonWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
Matthew FriemanDepartment of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0003-0107-0775
Benjamin R tenOeverDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0003-0324-3078
Donald E IngberWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA. don.ingber@wyss.harvard.edu.ORCID http://orcid.org/0000-0002-4319-6520
Icahn School of Medicine at Mount Sinai · USUniversity of Maryland, Baltimore · USBoston Children's Hospital · USHarvard University · USUniversity of Chieti-Pescara · ITUniversity of Pittsburgh · US

Funding

Lung-on-a-Chip Disease Models for Efficacy Testing (COVID-19 Competitive Revision)UH3HL141797 · NHLBI · HARVARD UNIVERSITY · PI INGBER, DONALD E · 2019 to 2021
$5.2M
Lung-on-a-Chip Disease Models for Efficacy TestingUG3HL141797 · NHLBI · HARVARD UNIVERSITY · PI INGBER, DONALD E · 2017 to 2018
$2.8M
NHLBI NIH HHS UG3 HL141797NHLBI NIH HHS UH3 HL141797
6 · The paper itself

Abstract

The rapid repurposing of antivirals is particularly pressing during pandemics. However, rapid assays for assessing candidate drugs typically involve in vitro screens and cell lines that do not recapitulate human physiology at the tissue and organ levels. Here we show that a microfluidic bronchial-airway-on-a-chip lined by highly differentiated human bronchial-airway epithelium and pulmonary endothelium can model viral infection, strain-dependent virulence, cytokine production and the recruitment of circulating immune cells. In airway chips infected with influenza A, the co-administration of nafamostat with oseltamivir doubled the treatment-time window for oseltamivir. In chips infected with pseudotyped severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), clinically relevant doses of the antimalarial drug amodiaquine inhibited infection but clinical doses of hydroxychloroquine and other antiviral drugs that inhibit the entry of pseudotyped SARS-CoV-2 in cell lines under static conditions did not. We also show that amodiaquine showed substantial prophylactic and therapeutic activities in hamsters challenged with native SARS-CoV-2. The human airway-on-a-chip may accelerate the identification of therapeutics and prophylactics with repurposing potential.

Indexed as

COVID-19 Drug TreatmentLab-On-A-Chip DevicesAnimalsAntiviral AgentsCell LineCOVID-19COVID-19 TestingCricetinaeFemaleGreen Fluorescent ProteinsHumansMaleSARS-CoV-2Virus InternalizationAntiviral AgentsGreen Fluorescent Proteins

Identifiers

PMID33941899
PMCPMC8387338
OpenAlexW3157288445

What OpenQuestion holds

Textmetadata
LicenceTDM
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.