Evidence map›Paper›PMID 39819574›Full record

ArticleRespiratory research2025

Optimization of a micro-scale air-liquid-interface model of human proximal airway epithelium for moderate throughput drug screening for SARS-CoV-2.

Chandani Sen, Tammy M Rickabaugh, Arjit Vijey Jeyachandran, Constance Yuen, Maisam Ghannam, Abdo Durra, Adam Aziz, Kristen Castillo, Gustavo Garcia, Arunima Purkayastha and 13 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Respiratory research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
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

23 authors.

Chandani SenDepartment of Pediatrics, David Geffen School of Medicine, UCLA Children's Discovery and Innovation Institute, Mattel Children's Hospital UCLA, UCLA, Los Angeles, CA, 90095, USA.
Tammy M RickabaughDepartment of Pediatrics, David Geffen School of Medicine, UCLA Children's Discovery and Innovation Institute, Mattel Children's Hospital UCLA, UCLA, Los Angeles, CA, 90095, USA.
Arjit Vijey JeyachandranDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA.
Constance YuenDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA.
Maisam GhannamDepartment of Pediatrics, David Geffen School of Medicine, UCLA Children's Discovery and Innovation Institute, Mattel Children's Hospital UCLA, UCLA, Los Angeles, CA, 90095, USA.
Abdo DurraDepartment of Pediatrics, David Geffen School of Medicine, UCLA Children's Discovery and Innovation Institute, Mattel Children's Hospital UCLA, UCLA, Los Angeles, CA, 90095, USA.
Adam AzizDepartment of Pediatrics, David Geffen School of Medicine, UCLA Children's Discovery and Innovation Institute, Mattel Children's Hospital UCLA, UCLA, Los Angeles, CA, 90095, USA.
Kristen CastilloDepartment of Pediatrics, David Geffen School of Medicine, UCLA Children's Discovery and Innovation Institute, Mattel Children's Hospital UCLA, UCLA, Los Angeles, CA, 90095, USA.
Gustavo GarciaDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA.
Arunima PurkayasthaDepartment of Pediatrics, David Geffen School of Medicine, UCLA Children's Discovery and Innovation Institute, Mattel Children's Hospital UCLA, UCLA, Los Angeles, CA, 90095, USA.
Brandon HanDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA.
Felix W BoultonDepartment of Pediatrics, David Geffen School of Medicine, UCLA Children's Discovery and Innovation Institute, Mattel Children's Hospital UCLA, UCLA, Los Angeles, CA, 90095, USA.
Eugene CheklerEMD Serono, Billerica, MA, 01821, USA.
Robert GarcesEMD Serono, Billerica, MA, 01821, USA.
Karen C WolffCalibr-Skaggs Institute for Innovative Medicines, 11119 North Torrey Pines Road, La Jolla, CA, 92037, USA.
Laura RivaCalibr-Skaggs Institute for Innovative Medicines, 11119 North Torrey Pines Road, La Jolla, CA, 92037, USA.
Melanie G KirkpatrickCalibr-Skaggs Institute for Innovative Medicines, 11119 North Torrey Pines Road, La Jolla, CA, 92037, USA.
Amal Gebara-LambCalibr-Skaggs Institute for Innovative Medicines, 11119 North Torrey Pines Road, La Jolla, CA, 92037, USA.
Case W McNamaraCalibr-Skaggs Institute for Innovative Medicines, 11119 North Torrey Pines Road, La Jolla, CA, 92037, USA.
Ulrich A K Betz *Merck KGaA, Darmstadt, Germany. ulrich.betz@merckgroup.com.
Vaithilingaraja Arumugaswami *Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA. varumugaswami@mednet.ucla.edu.
Robert Damoiseaux *Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA. rdamoiseaux@mednet.ucla.edu.
Brigitte N Gomperts *Department of Pediatrics, David Geffen School of Medicine, UCLA Children's Discovery and Innovation Institute, Mattel Children's Hospital UCLA, UCLA, Los Angeles, CA, 90095, USA. bgomperts@mednet.ucla.edu.ORCID http://orcid.org/0000-0002-1809-723X

Funding

UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1M
Developing a targeted chemoprevention strategy for Non-Small Cell Lung CancerR01CA208303 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GOMPERTS, BRIGITTE N · 2016 to 2020
$1.9M
Impact of Seasonal Variation in Hematocrit, NOx & ET-1 on Vascular ReactivityR21NR010361 · NINR · UNIVERSITY OF MISSOURI-COLUMBIA · PI WIPKE-TEVIS, DEIDRE D · 2008 to 2009
$401k
California Institute of Regenerative Medicine DISC2 19-11764NCATS NIH HHS UL1 TR001881NCI NIH HHS R01 CA208303NIH/NCI R01CA208303NINR NIH HHS R21 NR010361The Department of Defense PR202868UCOP Emergency Funding COVID19 TRDRP Seed grant R00RG2383
6 · The paper itself

Abstract

backgroundMany respiratory viruses attack the airway epithelium and cause a wide spectrum of diseases for which we have limited therapies. To date, a few primary human stem cell-based models of the proximal airway have been reported for drug discovery but scaling them up to a higher throughput platform remains a significant challenge. As a result, most of the drug screening assays for respiratory viruses are performed on commercial cell line-based 2D cultures that provide limited translational ability.

methodsWe optimized a primary human stem cell-based mucociliary airway epithelium model of SARS-CoV-2 infection, in 96-well air-liquid-interface (ALI) format, which is amenable to moderate throughput drug screening. We tested the model against SARS-CoV-2 parental strain (Wuhan) and variants Beta, Delta, and Omicron. We applied this model to screen 2100 compounds from targeted drug libraries using a high throughput-high content image-based quantification method.

resultsThe model recapitulated the heterogeneity of infection among patients with SARS-CoV-2 parental strain and variants. While there were heterogeneous responses across variants for host factor targeting compounds, the two direct-acting antivirals we tested, Remdesivir and Paxlovid, showed consistent efficacy in reducing infection across all variants and donors. Using the model, we characterized a new antiviral drug effective against both the parental strain and the Omicron variant.

conclusionThis study demonstrates that the 96-well ALI model of primary human mucociliary epithelium can recapitulate the heterogeneity of infection among different donors and SARS-CoV-2 variants and can be used for moderate throughput screening. Compounds that target host factors showed variability among patients in response to SARS-CoV-2, while direct-acting antivirals were effective against SARS-CoV-2 despite the heterogeneity of patients tested.

Indexed as

Antiviral AgentsCOVID-19COVID-19 Drug TreatmentHigh-Throughput Screening AssaysRespiratory MucosaSARS-CoV-2Cells, CulturedDrug Evaluation, PreclinicalHumansAntiviral AgentsAir–liquid-interfaceAnti-viral screeningHeterogeneityHigh throughput drug screeningHuman mucociliary epitheliumImage quantificationRespiratory viral infectionsRNA sequencingSARS-CoV-2Small-molecules

Identifiers

PMID39819574
PMCPMC11740480

What OpenQuestion holds

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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.