Evidence map›Paper›PMID 41468884›Full record

ArticleCell2026

Mechanisms of HSV-1 helicase-primase inhibition and replication fork complex assembly.

Zishuo Yu, Pradeep Sathyanarayana, Cong Liu, Joel M J Tan, Pan Yang, Biswajit Das, Side Hu, Xiaoyi Fan, Chenggong Ji, Sandra K Weller and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2026. 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. Article
  3. Article
  4. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Zishuo YuDepartment of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Pradeep SathyanarayanaDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Cong LiuCenter for the Development of Therapeutics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Joel M J TanDepartment of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.
Pan YangDepartment of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Biswajit DasDepartment of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Side HuDepartment of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Xiaoyi FanDepartment of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Chenggong JiDepartment of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Sandra K WellerDepartment of Molecular Biology and Biophysics, University of Connecticut School of Medicine, Farmington, CT, USA.
Mrinal ShekharCenter for the Development of Therapeutics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Donald M CoenDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Philip J KranzuschDepartment of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.
Joseph J LoparoDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA. Electronic address: joseph_loparo@hms.harvard.edu.
Jonathan AbrahamDepartment of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA; Department of Medicine, Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, USA; Center for Integrated Solutions for Infectious Diseases, Broad Institute of Harvard and MIT, Cambridge, MA, USA; Howard Hughes Medical Institute, Boston, MA, USA. Electronic address: jonathan_abraham@hms.harvard.edu.

Funding

GENETICS OF HSV DNA REPLICATIONR01AI021747 · NIAID · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI WELLER, SANDRA K, WRIGHT, DENNIS L. · 1985 to 2024
$9.9M
MOLECULAR GENETICS OF HSV DNA POLYMERASE GENER01AI019838 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI COEN, DONALD M, HOGLE, JAMES M · 1985 to 2015
$5.9M
Molecular mechanisms of pathway choice in DNA double strand break repairR01CA272436 · NCI · HARVARD MEDICAL SCHOOL · PI Joseph J. Loparo · 2022 to 2026
$1.9M
Structural studies of herpesvirus DNA polymerasesR21AI141940 · NIAID · HARVARD MEDICAL SCHOOL · PI ABRAHAM, JONATHAN, COEN, DONALD M · 2019 to 2020
$466k
NCI NIH HHS R01 CA272436NIAID NIH HHS R01 AI019838NIAID NIH HHS R01 AI021747NIAID NIH HHS R21 AI141940
6 · The paper itself

Abstract

Herpesviruses are widespread double-stranded DNA viruses that establish lifelong latency and cause various diseases. Although DNA-polymerase-targeting antivirals are effective, increasing drug resistance underscores the need for alternatives. Helicase-primase inhibitors (HPIs) are promising antivirals, but their mechanisms of action are poorly defined. Furthermore, how the helicase-primase (H/P) complex and DNA polymerase coordinate genome replication is not well understood for herpesviruses. Here, we report cryo-electron microscopy (cryo-EM) structures of the herpes simplex virus 1 H/P complex bound to HPIs, showing that these lock the H/P complex in an inactive state. Single-molecule assays reveal that HPIs cause H/P complexes to pause in unwinding activity on DNA. The structure of an HPI-bound replication fork complex, comprising the H/P complex (UL5, UL52, and UL8) and the polymerase holoenzyme (UL30 and UL42), reveals a previously uncharacterized interface bridging these complexes. These findings provide a structural framework for understanding herpesvirus replisome assembly and advancing inhibitor development.

Indexed as

DNA HelicasesDNA PrimaseDNA ReplicationHerpesvirus 1, HumanViral ProteinsAntiviral AgentsCryoelectron MicroscopyDNA-Directed DNA PolymeraseDNA, ViralEnzyme InhibitorsHumansModels, MolecularVirus ReplicationAntiviral AgentsDNA-Directed DNA PolymeraseDNA HelicasesDNA PrimaseDNA, ViralEnzyme Inhibitorshelicase-primase, Human herpesvirus 1Viral ProteinsantiviralDNA replicationhelicaseherpesviruspolymeraseprimase

Identifiers

PMID41468884
PMCPMC13082216

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.