Evidence map›Paper›PMID 39608645›Full record

ArticleAntiviral research2025

N-arylpyrimidinamine (NAPA) compounds are broadly acting inhibitors of human cytomegalovirus infection and spread.

Kristina E Atanasoff, Sabrina I Ophir, Andrea J Parsons, Jailene Paredes Casado, Nell S Lurain, Terry L Bowlin, Timothy J Opperman, Domenico Tortorella

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Antiviral research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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

8 authors.

Kristina E AtanasoffDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Sabrina I OphirDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Andrea J ParsonsDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Jailene Paredes CasadoDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Nell S LurainDepartment of Immunology-Microbiology, Rush University, Chicago, IL, USA.
Terry L BowlinMicrobiotix, Inc., Worcester, MA, 01605, USA.
Timothy J OppermanMicrobiotix, Inc., Worcester, MA, 01605, USA.
Domenico TortorellaDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. Electronic address: domenico.tortorella@mssm.edu.

Funding

TRAINING PROGRAM: MECHANISMS OF VIRUS-HOST INTERACTIONST32AI007647 · NIAID · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI Domenico Tortorella · 2000 to 2026
$11.5M
SYSTEMATIC DRUG REPURPOSING TARGETING IMMUNE ACTIVATION NETWORKS IN ALZHEIMER'S DISEASE (AD)RF1AG059319 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI EHRLICH, MICHELLE E, GANDY, SAMUEL E. · 2018 to 2018
$4.2M
Identification of human cytomegalovirus life cycle stage-specific therapeuticsR01AI139258 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI TORTORELLA, DOMENICO · 2019 to 2022
$1.6M
Optimization of novel inhibitors of human cytomegalovirusR56AI175974 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI TORTORELLA, DOMENICO · 2024 to 2024
$684k
Delineating the mechanism and inhibitory capacity of CMV neutralizing antibodiesR21AI147632 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI TORTORELLA, DOMENICO · 2020 to 2021
$465k
NIAID NIH HHS R01 AI139258NIAID NIH HHS R21 AI147632NIAID NIH HHS R56 AI175974NIAID NIH HHS T32 AI007647NIA NIH HHS RF1 AG059319
6 · The paper itself

Abstract

Human cytomegalovirus (HCMV) is a β-herpesvirus that contributes to the disease burden of immunocompromised and immunomodulated individuals, including transplant recipients and newborns. The FDA-approved HCMV drugs can exhibit drug resistance and severe side effects including bone marrow toxicity, gastrointestinal disruption, and nephrotoxicity. In a previous study, we identified the N-arylpyrimidinamine (NAPA) compound series as a new class of HCMV inhibitors that target early stages of infection. Here we describe the inhibitory activity of two potent NAPA analogs, MBXC-4336 and MBX-4992, that broadly block infection and spread. MBXC-4336 and MBX-4992 effectively inhibited infection by diverse HCMV strains and significantly prevented virus spread in fibroblast and epithelial cells as evaluated by quantifying infected cells and viral genome levels. Further, the NAPA compounds limited replication of clinical HCMV isolates, including a ganciclovir-resistant strain. Importantly, combination studies of NAPA compounds with ganciclovir demonstrated additive or synergistic inhibition of HCMV spread. Collectively, NAPA compounds have therapeutic potential for development as a novel class of anti-HCMV drugs.

Indexed as

Antiviral AgentsCytomegalovirusCytomegalovirus InfectionsVirus ReplicationCell LineDrug Resistance, ViralEpithelial CellsFibroblastsGanciclovirHumansAntiviral AgentsGanciclovirBroad spectrum antiviralsCombination therapyHuman cytomegalovirusNAPA compoundsSynergy

Identifiers

PMID39608645
PMCPMC12709849

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.