Evidence map›Paper›PMID 29113740›Full record

ArticleAntiviral research2018

Efficacy of pritelivir and acyclovir in the treatment of herpes simplex virus infections in a mouse model of herpes simplex encephalitis.

Debra C Quenelle, Alexander Birkmann, Thomas Goldner, Tamara Pfaff, Holger Zimmermann, Susanne Bonsmann, Deborah J Collins, Terri L Rice, Mark N Prichard

Open access · greenAbstract read
In one paragraph

Article in Antiviral research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.2field-weighted citation impact, top 20% 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

18 citing papers in PubMed, 36 citations in OpenAlex.

  1. Article
  2. Review
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  8. Article
  9. Review
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  11. Article
  12. Article
  13. Article
  14. Herpesvirus-Associated Encephalitis: an Update.Current tropical medicine reports · 2022
    Review
  15. Review
  16. Review
  17. A Preclinical Model for Studying Herpes Simplex Virus Infection.The Journal of investigative dermatology · 2019
    Article
  18. Insights into the pathogenesis of herpes simplex encephalitis from mouse models.Mammalian genome : official journal of the International Mammalian Genome Society · 2018
    Review
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

9 authors at 2 institutions in 2 countries.

Debra C QuenelleThe University of Alabama at Birmingham, School of Medicine, Birmingham, AL, USA.
Alexander BirkmannAiCuris Anti-Infective Cures GmbH, Wuppertal, Germany. Electronic address: alexander.birkmann@aicuris.com.
Thomas GoldnerAiCuris Anti-Infective Cures GmbH, Wuppertal, Germany.
Tamara PfaffAiCuris Anti-Infective Cures GmbH, Wuppertal, Germany.
Holger ZimmermannAiCuris Anti-Infective Cures GmbH, Wuppertal, Germany.
Susanne BonsmannAiCuris Anti-Infective Cures GmbH, Wuppertal, Germany.
Deborah J CollinsThe University of Alabama at Birmingham, School of Medicine, Birmingham, AL, USA.
Terri L RiceThe University of Alabama at Birmingham, School of Medicine, Birmingham, AL, USA.
Mark N PrichardThe University of Alabama at Birmingham, School of Medicine, Birmingham, AL, USA.
AiCuris (Germany) · DEUniversity of Alabama at Birmingham · US

Funding

NIAID NIH HHS HHSN272201000027CNIAID NIH HHS N01 AI015439
6 · The paper itself

Abstract

Pritelivir, a helicase-primase inhibitor, has excellent in vitro and in vivo activity against human herpes simplex virus (HSV). Mice lethally infected with HSV type 1 or 2, including acyclovir-resistant strains, were treated 72 h after infection for 7 days with pritelivir or acyclovir. Both drugs were administered orally twice daily either alone or in combination. Dosages of pritelivir from 0.3 to 30 mg/kg reduced mortality (P < 0.001) against HSV-1, E-377. With an acyclovir resistant HSV-1, 11360, pritelivir at 1 and 3 mg/kg increased survival (P < 0.005). With HSV-2, MS infected mice, all dosages higher than the 0.3 mg/kg dose of pritelivir were effective (P < 0.005). For acyclovir resistant HSV-2, strain 12247, pritelivir dosages of 1-3 mg/kg significantly improved survival (P < 0.0001). Combination therapies of pritelivir at 0.1 or 0.3 mg/kg/dose with acyclovir (10 mg/kg/dose) were protective (P < 0.0001) when compared to the vehicle treated group against HSV-2, strain MS (in line with previous data using HSV-1). An increased mean days to death (P < 0.05) was also observed and was indicative of a potential synergy. Pharmacokinetic studies were performed to determine pritelivir concentrations and a dose dependent relationship was found in both plasma and brain samples regardless of infection status or time of initiation of dosing. In summary, pritelivir was shown to be active when treatment was delayed to 72 h post viral inoculation and appeared to synergistically inhibit mortality in this model in combination with acyclovir. We conclude pritelivir has potent and resistance-breaking antiviral efficacy with potential for the treatment of potentially life-threatening HSV type 1 and 2 infections, including herpes simplex encephalitis.

Indexed as

AcyclovirAnimalsAntiviral AgentsDisease Models, AnimalDrug Therapy, CombinationEncephalitis, Herpes SimplexFemaleHumansMicePyridinesSulfonamidesThiazolesTissue DistributionTreatment OutcomeAcyclovirAntiviral AgentspritelivirPyridinesSulfonamidesThiazolesAntiviral therapyCombinationEfficacyHerpes simplex encephalitisMurine model

Identifiers

PMID29113740
PMCPMC5743594
OpenAlexW2766523073

What OpenQuestion holds

Textmetadata
LicenceTDM
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.