Evidence map›Paper›PMID 32824616›Full record

ArticleViruses2020

Combinatorial Treatment of Birinapant and Zosuquidar Enhances Effective Control of HBV Replication In Vivo.

Emma Morrish, Liana Mackiewicz, Natasha Silke, Marc Pellegrini, John Silke, Gabriela Brumatti, Gregor Ebert

Open access · goldAbstract read
In one paragraph

Article in Viruses, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.0field-weighted citation impact, top 22% 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

9 citing papers in PubMed, 11 citations in OpenAlex.

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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

7 authors at 2 institutions in 1 country.

Emma MorrishThe Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia.
Liana MackiewiczThe Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia.
Natasha SilkeThe Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia.ORCID 0000-0002-2271-7980
Marc PellegriniThe Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia.
John SilkeThe Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia.ORCID 0000-0002-7611-5774
Gabriela BrumattiThe Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia.
Gregor EbertThe Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia.ORCID 0000-0002-5318-3037
The University of Melbourne · AUWalter and Eliza Hall Institute of Medical Research · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chronic hepatitis B virus (HBV) infection remains a global health threat and affects hundreds of millions worldwide. Small molecule compounds that mimic natural antagonists of inhibitor of apoptosis (IAP) proteins, known as Smac-mimetics (second mitochondria-derived activator of caspases-mimetics), can promote the death of HBV-replicating liver cells and promote clearance of infection in preclinical models of HBV infection. The Smac-mimetic birinapant is a substrate of the multidrug resistance protein 1 (MDR1) efflux pump, and therefore inhibitors of MDR1 increase intracellular concentration of birinapant in MDR1 expressing cells. Liver cells are known to express MDR1 and other drug pump proteins. In this study, we investigated whether combining the clinical drugs, birinapant and the MDR1 inhibitor zosuquidar, increases the efficacy of birinapant in killing HBV expressing liver cells. We showed that this combination treatment is well tolerated and, compared to birinapant single agent, was more efficient at inducing death of HBV-positive liver cells and improving HBV-DNA and HBV surface antigen (HBsAg) control kinetics in an immunocompetent mouse model of HBV infection. Thus, this study identifies a novel and safe combinatorial treatment strategy to potentiate substantial reduction of HBV replication using an IAP antagonist.

Indexed as

AnimalsAntiviral AgentsATP Binding Cassette Transporter, Subfamily B, Member 1DibenzocycloheptenesDipeptidesDisease Models, AnimalDrug Therapy, CombinationHepatitis B, ChronicHepatitis B virusHep G2 CellsHumansIndolesInhibitor of Apoptosis ProteinsLiverMaleMiceAntiviral AgentsATP Binding Cassette Transporter, Subfamily B, Member 1birinapantDibenzocycloheptenesDipeptidesIndolesInhibitor of Apoptosis ProteinsQuinolineszosuquidar trihydrochloridecell deathcombination therapyHBVIAPIAP antagonistinhibitor of apoptosis proteinsMDR1 inhibitorSmac-mimeticsTNF

Identifiers

PMID32824616
PMCPMC7472335
OpenAlexW3049269638

What OpenQuestion holds

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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.