Evidence map›Paper›PMID 42282544›Full record

ArticlebioRxiv : the preprint server for biology2026

Viral Nuclease Inhibitors: Small molecule disruptors of the UL12 alkaline nuclease display broad anti-herpes virus activity.

Nidhi Sharma, Xiaoyun Xie, Renata Szczepaniak, Chitra Rani, Sheida Khojasteh Khosro, Jolanta Krucinska, Xiaoling Chen, Dung Do, Lee Wright, Dennis Wright and 1 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Nidhi SharmaDepartment of Molecular Biology and Biophysics, University of Connecticut School of Medicine, Farmington, Connecticut, USA.
Xiaoyun XieDepartment of Pharmaceutical Sciences, University of Connecticut School of Pharmacy, Storrs, Connecticut, USA.
Renata SzczepaniakDepartment of Molecular Biology and Biophysics, University of Connecticut School of Medicine, Farmington, Connecticut, USA.
Chitra RaniDepartment of Molecular Biology and Biophysics, University of Connecticut School of Medicine, Farmington, Connecticut, USA.
Sheida Khojasteh KhosroDepartment of Chemistry, University of Connecticut School of Pharmacy, Storrs, Connecticut, USA.
Jolanta KrucinskaDepartment of Pharmaceutical Sciences, University of Connecticut School of Pharmacy, Storrs, Connecticut, USA.
Xiaoling ChenDepartment of Pharmaceutical Sciences, University of Connecticut School of Pharmacy, Storrs, Connecticut, USA.
Dung DoDepartment of Pharmaceutical Sciences, University of Connecticut School of Pharmacy, Storrs, Connecticut, USA.
Lee WrightDepartment of Pharmaceutical Sciences, University of Connecticut School of Pharmacy, Storrs, Connecticut, USA.
Dennis WrightDepartment of Pharmaceutical Sciences, University of Connecticut School of Pharmacy, Storrs, Connecticut, USA.
Sandra WellerDepartment of Molecular Biology and Biophysics, University of Connecticut School of Medicine, Farmington, Connecticut, USA.

Funding

Exploring herpesvirus exonucleases as potential antiviral targetsR56AI173955 · NIAID · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI WELLER, SANDRA K, WRIGHT, DENNIS L. · 2023 to 2023
$605k
Microscale Thermophoresis Instrument System for UCONN Biophysics Core FacilityS10OD028574 · OD · UNIVERSITY OF CONNECTICUT STORRS · PI ERLANDSEN, HEIDI · 2021 to 2021
$191k
NIAID NIH HHS R56 AI173955NIH HHS S10 OD028574
6 · The paper itself

Abstract

Herpes simplex virus-1 (HSV-1) UL12 gene encodes a well-conserved 5' → 3' alkaline exonuclease. UL12 collaborates with the HSV single-strand DNA binding protein ICP8 to mediate recombination-dependent replication of viral DNA and is essential for the production of DNA that can be packaged into infectious virus. The UL12 gene has orthologs in the eight other human herpesviruses, including UL98 in HCMV and SOX in KSHV, which are also essential for virus production. We have developed viral nuclease inhibitors (VNIs) of HSV-1 UL12 that potently block its nuclease activity and display strong antiviral effects in cell culture. These inhibitors are also effective against alkaline nucleases from the β-HHV HCMV (UL98) and the γ-HHV KSHV (SOX), and we have demonstrated antiviral activity against HSV-1 and HCMV in cell culture. In this work, we describe the first crystal structure of an alphaherpesvirus alkaline nuclease (UL12.5), which was used to elucidate structure activity relationships and improve the selectivity of our inhibitors. These VNIs exhibit EC

Indexed as

alkaline nucleaseantiviral therapyBiochemistryenzyme inhibitorsEnzymologyHerpes simplex virusMedicinal Chemistrytwo-metal ion-dependent enzymesVirology

Identifiers

PMID42282544
PMCPMC13252101

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.