Evidence map›Paper›PMID 41931535›Full record

ArticlePLoS pathogens2026

Discovery of a potent anti-Zika virus benzamide series targeting the viral protein NS4B.

Donghoon Chung, Yuka Otsuka, Eunjung Kim, Sultan Ullah, Nicole M Kennedy, Khac Huy Ngo, Jinjoo Kang, Reece Tomlinson, Brian Alejandro, Koji Barnaby and 10 more

Abstract read
In one paragraph

Article in PLoS pathogens, 2026. 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

5 · Who and what money

Authors and funding

20 authors.

Donghoon ChungCenter for Predictive Medicine, Department of Microbiology Immunology, School of Medicine, University of Louisville, Louisville, Kentucky, United States of America.ORCID https://orcid.org/0000-0003-2626-172X
Yuka OtsukaDepartment of Molecular Medicine, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technology, Jupiter, Florida, United States of America.
Eunjung KimCenter for Predictive Medicine, Department of Microbiology Immunology, School of Medicine, University of Louisville, Louisville, Kentucky, United States of America.
Sultan UllahDepartment of Molecular Medicine, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technology, Jupiter, Florida, United States of America.
Nicole M KennedyDepartment of Molecular Medicine, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technology, Jupiter, Florida, United States of America.
Khac Huy NgoLee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
Jinjoo KangCenter for Predictive Medicine, Department of Microbiology Immunology, School of Medicine, University of Louisville, Louisville, Kentucky, United States of America.
Reece TomlinsonCenter for Predictive Medicine, Department of Microbiology Immunology, School of Medicine, University of Louisville, Louisville, Kentucky, United States of America.
Brian AlejandroCenter for Predictive Medicine, Department of Microbiology Immunology, School of Medicine, University of Louisville, Louisville, Kentucky, United States of America.
Koji BarnabyCenter for Predictive Medicine, Department of Microbiology Immunology, School of Medicine, University of Louisville, Louisville, Kentucky, United States of America.
Jeffrey MillerCenter for Predictive Medicine, Department of Microbiology Immunology, School of Medicine, University of Louisville, Louisville, Kentucky, United States of America.
Justin ShumateDepartment of Molecular Medicine, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technology, Jupiter, Florida, United States of America.
Chwee Fang TeoLee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
Yaw Bia TanLee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
Che Shin ChewLee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
CongBao KangExperimental Drug Development Centre, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
Dahai LuoLee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
Louis ScampaviaDepartment of Molecular Medicine, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technology, Jupiter, Florida, United States of America.
Timothy P SpicerDepartment of Molecular Medicine, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technology, Jupiter, Florida, United States of America.
Thomas D BannisterDepartment of Molecular Medicine, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technology, Jupiter, Florida, United States of America.

Funding

Project 5: Pandemic Virus Helicase InhibitorsU19AI171954 · NIAID · UNIVERSITY OF MINNESOTA · PI Reuben S Harris, Fang Li · 2022 to 2026
$100.9M
NIAID NIH HHS U19 AI171954
6 · The paper itself

Abstract

Zika virus (ZIKV), a member of the Flaviviridae family, causes significant public health concerns through congenital Zika syndrome and Guillain-Barré syndrome, yet no effective anti-ZIKV drugs or vaccines are available. To address this critical need, we conducted phenotypic, cytopathic effect-based high-throughput screening followed by medicinal chemistry optimization and discovered novel benzamide anti-ZIKV leads. Current best compounds demonstrated superior potency (EC50 values 40-400 nM, CC50 > 50 µM) compared to NITD-008, the most potent known anti-ZIKV agent. Time-of-addition assays, resistant virus selection studies, and biophysical binding experiments confirmed that NS4B interference constitutes the primary antiviral mechanism. Notably, resistance mutations mapped to the C-terminus of NS4B, distinct from other flavivirus NS4B inhibitors targeting dengue or yellow fever viruses, revealing novel insights into a critical function of the region. These findings establish NS4B as an Achilles' heel for flaviviruses and support the development of pan-flavivirus therapeutics targeting this essential viral protein.

Indexed as

Antiviral AgentsBenzamidesViral Nonstructural ProteinsZika VirusZika Virus InfectionAnimalsDrug DiscoveryDrug Resistance, ViralHumansVirus ReplicationAntiviral AgentsBenzamidesNS4B protein, flavivirusViral Nonstructural Proteins

Identifiers

PMID41931535
PMCPMC13065080

What OpenQuestion holds

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LicenceCC BY
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.