Evidence map›Paper›PMID 36717567›Full record

ArticleScientific reports2023

Truncated ring-A amaryllidaceae alkaloid modulates the host cell integrated stress response, exhibiting antiviral activity to HSV-1 and SARSCoV-2.

James McNulty, Chanti Babu-Dokuburra, Jon Scattolon, Carlos Zepeda-Velazquez, Maribeth A Wesesky, Jill K Caldwell, Wenxiao Zheng, Jadranka Milosevic, Paul R Kinchington, David C Bloom and 2 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2023. 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
1.2field-weighted citation impact, top 25% of its field
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, 8 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. 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

12 authors at 5 institutions in 3 countries.

James McNultyDepartment of Chemistry & Chemical Biology, McMaster University, Hamilton, ON, L8S 4M1, Canada. jmcnult@mcmaster.ca.
Chanti Babu-DokuburraDepartment of Chemistry & Chemical Biology, McMaster University, Hamilton, ON, L8S 4M1, Canada.
Jon ScattolonDepartment of Chemistry & Chemical Biology, McMaster University, Hamilton, ON, L8S 4M1, Canada.
Carlos Zepeda-VelazquezDepartment of Chemistry & Chemical Biology, McMaster University, Hamilton, ON, L8S 4M1, Canada.
Maribeth A WeseskyDepartment of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA.
Jill K CaldwellDepartment of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA.
Wenxiao ZhengDepartment of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA.
Jadranka MilosevicDepartment of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA, USA.
Paul R KinchingtonDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
David C BloomDepartment of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL, 32610, USA.
Vishwajit L NimgaonkarDepartment of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA.
Leonardo D'AiutoDepartment of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA. daiutol@upmc.edu.
University of Pittsburgh · USMcMaster University · CACarnegie Mellon University · USUniversity of Florida · USVA Pittsburgh Healthcare System · US

Funding

Virus Production and Manipulation of Protein/Gene Expression ModuleP30EY008098 · NEI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Yuanyuan Chen · 1989 to 2026
$17.8M
Effects of HSV-1 reactivation from latency on aspects of neural precursor cells neurogenesis and accumulation of Alzheimer's molecular hallmarksR01NS115082 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BLOOM, DAVID C., D'AIUTO, LEONARDO · 2020 to 2024
$2.3M
Analysis of human-specific aspects of HSV-1 latency in human iPSC-derived neuronsR21NS096405 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI D'AIUTO, LEONARDO · 2016 to 2017
$428k
NEI NIH HHS P30 EY008098NINDS NIH HHS R01 NS115082NINDS NIH HHS R21 NS096405
6 · The paper itself

Abstract

The total synthesis of four novel mono-methoxy and hydroxyl substituted ring-A dihydronarciclasine derivatives enabled identification of the 7-hydroxyl derivative as a potent and selective antiviral agent targeting SARSCoV-2 and HSV-1. The concentration of this small molecule that inhibited HSV-1 infection by 50% (IC50), determined by using induced pluripotent stem cells (iPCS)-derived brain organ organoids generated from two iPCS lines, was estimated to be 0.504 µM and 0.209 µM. No significant reduction in organoid viability was observed at concentrations up to 50 mM. Genomic expression analyses revealed a significant effect on host-cell innate immunity, revealing activation of the integrated stress response via PERK kinase upregulation, phosphorylation of eukaryotic initiation factor 2α (eIF2α) and type I IFN, as factors potentiating multiple host-defense mechanisms against viral infection. Following infection of mouse eyes with HSV-1, treatment with the compound dramatically reduced HSV-1 shedding in vivo.

Indexed as

Amaryllidaceae AlkaloidsAntineoplastic AgentsHerpesvirus 1, HumanInterferon Type IAnimalsAntiviral AgentsMicePhosphorylationAmaryllidaceae AlkaloidsAntineoplastic AgentsAntiviral AgentsInterferon Type I

Identifiers

PMID36717567
PMCPMC9885069
OpenAlexW4318478378

What OpenQuestion holds

Textmetadata
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.