Evidence map›Paper›PMID 30413769›Full record

ArticleScientific reports2018

R430: A potent inhibitor of DNA and RNA viruses.

Leonardo D'Aiuto, James McNulty, Caroll Hartline, Matthew Demers, Raj Kalkeri, Joel Wood, Lora McClain, Ansuman Chattopadhyay, Yun Zhi, Jennifer Naciri and 12 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.7field-weighted citation impact, top 34% 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

6 citing papers in PubMed, 12 citations in OpenAlex.

  1. Review
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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

22 authors at 8 institutions in 3 countries.

Leonardo D'AiutoDepartment of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, 3811 O'Hara Street, Pittsburgh, PA, 15213, USA.
James McNultyDepartment of Chemistry and Chemical-Biology, McMaster University, 1280 Main Street West, Hamilton, Ontario, L8S 4M1, Canada.ORCID http://orcid.org/0000-0002-7123-7588
Caroll HartlineUniversity of Alabama at Birmingham, UAB School of Medicine, 1720 2nd Ave. S., Birmingham, AL, 35294-3412, USA.
Matthew DemersDepartment of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, 3811 O'Hara Street, Pittsburgh, PA, 15213, USA.
Raj KalkeriDepartment of Infectious Disease Research, Drug Development, Southern Research Institute, 431 Aviation Way, Frederick, Maryland, 21701, USA.
Joel WoodDepartment of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, 3811 O'Hara Street, Pittsburgh, PA, 15213, USA.
Lora McClainMagee-Women's Research Institute, 204 Craft Ave, Pittsburgh, PA, 15213, USA.
Ansuman ChattopadhyayMolecular Biology Information Service, Health Sciences Library System, 3550 Terrace Street, Pittsburgh, PA, 15261, USA.
Yun ZhiDepartment of Pharmacology and Pharmaceutical Sciences, School of Medicine, Tsinghua University, Beijing, China.
Jennifer NaciriDepartment of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, 3811 O'Hara Street, Pittsburgh, PA, 15213, USA.
Adam SmithDepartment of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, 3811 O'Hara Street, Pittsburgh, PA, 15213, USA.
Robert YolkenDivision of Neurovirology, Department of Pediatrics, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Blalock 1105, Baltimore, MD, 21287, USA.
Kodavali ChowdariDepartment of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, 3811 O'Hara Street, Pittsburgh, PA, 15213, USA.
Carlos Zepeda-VelazquezDepartment of Chemistry and Chemical-Biology, McMaster University, 1280 Main Street West, Hamilton, Ontario, L8S 4M1, Canada.
Chanti Babu DokuburraDepartment of Chemistry and Chemical-Biology, McMaster University, 1280 Main Street West, Hamilton, Ontario, L8S 4M1, Canada.
Ernesto MarquesUniversity of Pittsburgh, Department of Infectious Diseases and Microbiology, 9022 BST3, 3501 Fifth Avenue, Pittsburgh, PA, 15260, USA.
Roger PtakDepartment of Infectious Disease Research, Drug Development, Southern Research Institute, 431 Aviation Way, Frederick, Maryland, 21701, USA.
Paul KinchingtonDepartment of Ophthalmology, University of Pittsburgh School of Medicine, 1016 Eye and Ear Institute, Pittsburgh, PA, 15213, USA.
Simon WatkinsDepartment of Cell Biology, University of Pittsburgh, 3500 Terrace Street, S362 Biomedical Science Tower (South), Pittsburgh, PA, 15261, USA.
Mark PrichardUniversity of Alabama at Birmingham, UAB School of Medicine, 1720 2nd Ave. S., Birmingham, AL, 35294-3412, USA.
David BloomDepartment of Molecular Genetics & Microbiology, University of Florida College of Medicine, Box 100266 JHMHC, Gainesville, FL, 32610-0266, USA.ORCID http://orcid.org/0000-0001-5935-8494
Vishwajit NimgaonkarDepartment of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, 3811 O'Hara Street, Pittsburgh, PA, 15213, USA. vishwajitNL@upmc.edu.ORCID http://orcid.org/0000-0001-8485-5927
University of Pittsburgh · USMcMaster University · CASouthern Research Institute · USUniversity of Alabama at Birmingham · USJohns Hopkins University · USMagee-Womens Research Institute · USTsinghua University · CNUniversity of Florida · US

Funding

XRAY CRYSTALLOGRAPHYP30CA013148 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Robert S Welner · 1985 to 2026
$165.9M
Virus Production and Manipulation of Protein/Gene Expression ModuleP30EY008098 · NEI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Ethan A Rossi · 1989 to 2026
$17.8M
A Neurobehavioral Family Study of SchizophreniaR01MH063480 · NIMH · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI NIMGAONKAR, VISHWAJIT LAXMIKANT · 2001 to 2018
$6.1M
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
NCI NIH HHS P30 CA013148NEI NIH HHS P30 EY008098NIAID NIH HHS HHSN272201100016CNIMH NIH HHS R01 MH063480NINDS NIH HHS R21 NS096405Stanley Medical Research Institute (SMRI) 07R-1712
6 · The paper itself

Abstract

Acyclovir (ACV) is an effective antiviral agent for treating lytic Herpes Simplex virus, type 1 (HSV-1) infections, and it has dramatically reduced the mortality rate of herpes simplex encephalitis. However, HSV-1 resistance to ACV and its derivatives is being increasingly documented, particularly among immunocompromised individuals. The burgeoning drug resistance compels the search for a new generation of more efficacious anti-herpetic drugs. We have previously shown that trans-dihydrolycoricidine (R430), a lycorane-type alkaloid derivative, effectively inhibits HSV-1 infections in cultured cells. We now report that R430 also inhibits ACV-resistant HSV-1 strains, accompanied by global inhibition of viral gene transcription and enrichment of H3K27me3 methylation on viral gene promoters. Furthermore, we demonstrate that R430 prevents HSV-1 reactivation from latency in an ex vivo rodent model. Finally, among a panel of DNA viruses and RNA viruses, R430 inhibited Zika virus with high therapeutic index. Its therapeutic index is comparable to standard antiviral drugs, though it has greater toxicity in non-neuronal cells than in neuronal cells. Synthesis of additional derivatives could enable more efficacious antivirals and the identification of active pharmacophores.

Indexed as

Amaryllidaceae AlkaloidsAnimalsAntiviral AgentsCells, CulturedChlorocebus aethiopsDNA VirusesDNA Virus InfectionsHumansMiceRNA VirusesRNA Virus InfectionsVero CellsVirus ReplicationAmaryllidaceae AlkaloidsAntiviral Agentstrans-dihydrolycoricidine

Identifiers

PMID30413769
PMCPMC6226428
OpenAlexW2900064643

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.