Evidence map›Paper›PMID 41102222›Full record

ArticleNature communications2025

Limitations of acyclovir and identification of potent HSV antivirals using 3D bioprinted human skin equivalents.

S Tori Ellison, Ian Hayman, Kristy Derr, Paige Derr, Shayne Frebert, Zina Itkin, Min Shen, Anthony Jones, Wendy Olson, Lawrence Corey and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

S Tori Ellison *Department of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA.
Ian Hayman *Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, USA.
Kristy DerrDepartment of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA.
Paige DerrDepartment of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA.
Shayne FrebertDepartment of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA.
Zina ItkinDepartment of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA.
Min ShenDepartment of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA.
Anthony JonesDepartment of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, USA.
Wendy OlsonDepartment of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, USA.
Lawrence CoreyDepartment of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-2179-2436
Anna WaldDepartment of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, USA.ORCID http://orcid.org/0000-0003-3486-6438
Christine JohnstonDepartment of Medicine, University of Washington School of Medicine, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-3073-0843
Youyi FongVaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-4230-6863
Marc FerrerDepartment of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA. marc.ferrer@nih.gov.ORCID http://orcid.org/0000-0003-4569-9137
Jia ZhuDepartment of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, USA. jiazhu@uw.edu.ORCID http://orcid.org/0000-0002-8676-5105

Funding

VENEREAL DISEASET32AI007140 · NIAID · UNIVERSITY OF WASHINGTON · PI Julia Cook Dombrowski · 1985 to 2026
$19.4M
Modeling of human HSV infection: development of immune-competent 3D skin-on-chip with vascular perfusionR01AI143773 · NIAID · UNIVERSITY OF WASHINGTON · PI ZHU, JIA · 2020 to 2024
$2.7M
Cross talk between keratinocytes and skin-resident T-cells influences HSV recurrenceR01AI184778 · NIAID · FRED HUTCHINSON CANCER CENTER · PI Jia Zhu · 2024 to 2026
$2.6M
Biofabricated 3-D skin model for antiviral drug discovery against human HSV infectionU18TR003208 · NCATS · UNIVERSITY OF WASHINGTON · PI ZHU, JIA · 2020 to 2021
$1.0M
NCATS NIH HHS U18 TR003208NIAID NIH HHS R01 AI143773NIAID NIH HHS R01 AI184778NIAID NIH HHS T32 AI007140U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences (NCATS) U18 TR0033208U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) T32 AI07140
6 · The paper itself

Abstract

Herpes simplex virus (HSV) infection poses global public health concerns with lifelong impacts. Acyclovir, the standard therapy, has limited efficacy in preventing subclinical shedding, and drug resistance occurs in immunocompromised patients, highlighting the need for novel therapeutics. Here we show that acyclovir is significantly less effective in skin-derived keratinocytes than donor-matched fibroblasts. Using 3D bioprinted human skin equivalents (HSEs) in a 96-well plate format, we have screened 738 compounds with broad targets and mechanisms of action, identifying potent antivirals, including 23 known or experimental HSV treatments. Unlike acyclovir, antivirals against HSV helicase/primase or host replication pathways display similar potency across cell types and donor sources in both 2D and 3D models. The reduced potency in keratinocytes may explain acyclovir's limited clinical efficacy. Our 3D bioprinted HSE assay platform enables the integration of patient-derived cells early in drug development and offers a physiologically relevant approach for HSV drug discovery.

Indexed as

AcyclovirAntiviral AgentsHerpes SimplexSimplexvirusSkinBioprintingFibroblastsHumansKeratinocytesPrinting, Three-DimensionalVirus ReplicationAcyclovirAntiviral Agents

Identifiers

PMID41102222
PMCPMC12533247

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.