Evidence map›Paper›PMID 39762652›Full record

ArticleMolecular systems biology2025

A multiplex method for rapidly identifying viral protease inhibitors.

Seo Jung Hong, Samuel J Resnick, Sho Iketani, Ji Won Cha, Benjamin Alexander Albert, Christopher T Fazekas, Ching-Wen Chang, Hengrui Liu, Shlomi Dagan, Michael R Abagyan and 14 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular systems biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

24 authors.

Seo Jung Hong *Department of Pathology and Cell Biology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA.
Samuel J Resnick *Department of Pathology and Cell Biology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA.ORCID http://orcid.org/0000-0003-1224-2114
Sho Iketani *Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA.ORCID http://orcid.org/0000-0002-3733-9556
Ji Won ChaDepartment of Pediatrics, University of California San Diego, La Jolla, CA, 92123, USA.
Benjamin Alexander AlbertDepartment of Pediatrics, University of California San Diego, La Jolla, CA, 92123, USA.ORCID http://orcid.org/0000-0002-8989-077X
Christopher T FazekasDepartment of Pediatrics, University of California San Diego, La Jolla, CA, 92123, USA.
Ching-Wen ChangDivision of Infectious Diseases, Department of Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA.ORCID http://orcid.org/0009-0006-0892-7419
Hengrui LiuDepartment of Biological Sciences, Department of Chemistry, and Department of Pathology and Cell Biology, Columbia University, New York, NY, 10032, USA.
Shlomi DaganFisher Drug Discovery Resource Center, The Rockefeller University, New York, NY, 10065, USA.
Michael R AbagyanSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, 92093, USA.
Pavla FajtováSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, 92093, USA.
Bruce CulbertsonMedical Scientist Training Program, Columbia University Irving Medical Center, New York, NY, 10032, USA.
Brooklyn BraceDepartment of Pathology and Cell Biology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA.ORCID http://orcid.org/0000-0001-5009-6125
Eswar R ReddemDepartment of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, 10032, USA.
Farhad ForouharDepartment of Pathology and Cell Biology and Columbia University Digestive and Liver Disease Research Center, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, 10032, USA.ORCID http://orcid.org/0000-0002-5571-7397
J Fraser GlickmanFisher Drug Discovery Resource Center, The Rockefeller University, New York, NY, 10065, USA.ORCID http://orcid.org/0000-0002-6706-4039
James M BalkovecCenter for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ, 07110, USA.
Brent R StockwellDepartment of Biological Sciences, Department of Chemistry, and Department of Pathology and Cell Biology, Columbia University, New York, NY, 10032, USA.ORCID http://orcid.org/0000-0002-3532-3868
Lawrence ShapiroAaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA.
Anthony J O'DonoghueSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, 92093, USA.
Yosef SaboAaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA.
Joel S FreundlichDepartment of Pharmacology, Physiology, and Neuroscience, Rutgers University - New Jersey Medical School, Newark, NJ, 07103, USA.
David D HoAaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA.
Alejandro ChavezDepartment of Pathology and Cell Biology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA. chavez2@health.ucsd.edu.ORCID http://orcid.org/0000-0001-5626-7140

Funding

Burroughs Wellcome Fund (BWF) 1017195.01HHS | National Institutes of Health (NIH) 1U19AI1711401jack ma foundation N/ANSF | National Science Foundation Graduate Research Fellowship Program (GRFP) DGE-2038238
6 · The paper itself

Abstract

With current treatments addressing only a fraction of pathogens and new viral threats constantly evolving, there is a critical need to expand our existing therapeutic arsenal. To speed the rate of discovery and better prepare against future threats, we establish a high-throughput platform capable of screening compounds against 40 diverse viral proteases simultaneously. This multiplex approach is enabled by using cellular biosensors of viral protease activity combined with DNA-barcoding technology, as well as several design innovations that increase assay sensitivity and correct for plate-to-plate variation. Among >100,000 compound-target interactions explored within our initial screen, a series of broad-acting inhibitors against coronavirus proteases were uncovered and validated through orthogonal assays. A medicinal chemistry campaign was performed to improve one of the inhibitor's potency while maintaining its broad activity. This work highlights the power of multiplex screening to efficiently explore chemical space at a fraction of the time and costs of previous approaches.

Indexed as

Antiviral AgentsHigh-Throughput Screening AssaysViral Protease InhibitorsViral ProteasesBiosensing TechniquesDrug DiscoveryHumansSARS-CoV-2Antiviral AgentsViral Protease InhibitorsViral ProteasesAntiviralBiosensorsDrug ScreeningHigh-ThroughputMultiplex

Identifiers

PMID39762652
PMCPMC11790949

What OpenQuestion holds

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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.