Evidence map›Paper›PMID 39013947›Full record

ArticleScientific reports2024

Analysis of the susceptibility of refractory hepatitis C virus resistant to nonstructural 5A inhibitors.

Ai Toyodome, Seiichi Mawatari, Hiromi Eguchi, Midori Takeda, Kotaro Kumagai, Ohki Taniyama, Sho Ijuin, Haruka Sakae, Kazuaki Tabu, Kohei Oda and 2 more

Abstract read
In one paragraph

Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. 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.

Ai ToyodomeDigestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, 8‑35‑1 Sakuragaoka, Kagoshima, 890‑8544, Japan.
Seiichi MawatariDigestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, 8‑35‑1 Sakuragaoka, Kagoshima, 890‑8544, Japan. mawatari@m2.kufm.kagoshima-u.ac.jp.
Hiromi EguchiDigestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, 8‑35‑1 Sakuragaoka, Kagoshima, 890‑8544, Japan.
Midori TakedaDivision of Biological Information Technology, Joint Research Center for Human Retrovirus Infection, Kagoshima University, 8‑35‑1 Sakuragaoka, Kagoshima, 890‑8544, Japan.
Kotaro KumagaiDigestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, 8‑35‑1 Sakuragaoka, Kagoshima, 890‑8544, Japan.
Ohki TaniyamaDigestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, 8‑35‑1 Sakuragaoka, Kagoshima, 890‑8544, Japan.
Sho IjuinDigestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, 8‑35‑1 Sakuragaoka, Kagoshima, 890‑8544, Japan.
Haruka SakaeDigestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, 8‑35‑1 Sakuragaoka, Kagoshima, 890‑8544, Japan.
Kazuaki TabuDigestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, 8‑35‑1 Sakuragaoka, Kagoshima, 890‑8544, Japan.
Kohei OdaDigestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, 8‑35‑1 Sakuragaoka, Kagoshima, 890‑8544, Japan.
Masanori IkedaDivision of Biological Information Technology, Joint Research Center for Human Retrovirus Infection, Kagoshima University, 8‑35‑1 Sakuragaoka, Kagoshima, 890‑8544, Japan.
Akio IdoDigestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, 8‑35‑1 Sakuragaoka, Kagoshima, 890‑8544, Japan.

Funding

Grant-in-Aid for Research on Hepatitis from the Ministry of Health Labor and Welfare of Japan JP20fk0210058
6 · The paper itself

Abstract

Resistance-associated substitutions (RASs) of hepatitis C virus (HCV) affect the efficacy of direct-acting antivirals (DAAs). In this study, we aimed to clarify the susceptibility of the coexistence of nonstructural (NS) 5A Q24K/L28M/R30Q (or R30E)/A92K RASs, which were observed in patients with DAAs re-treatment failure and to consider new therapeutic agents. We used a subgenomic replicon system in which HCV genotype 1B strain 1B-4 was electroporated into OR6c cells derived from HuH-7 cells (Wild-type [WT]). We converted WT genes to NS5A Q24K/L28M/R30Q/A92K or Q24/L28K/R30E/A92K. Compared with the WT, the Q24K/L28M/R30Q/A92K RASs was 36,000-fold resistant to daclatasvir, 440,000-fold resistant to ledipasvir, 6300-fold resistant to velpatasvir, 3100-fold resistant to elbasvir, and 1.8-fold resistant to pibrentasvir. Compared with the WT, the Q24K/L28M/R30E/A92K RASs was 640,000-fold resistant to daclatasvir and ledipasvir, 150,000-fold resistant to velpatasvir, 44,000-fold resistant to elbasvir, and 1500-fold resistant to pibrentasvir. The Q24K/L28M/R30E/A92K RASs was 816.3 times more resistant to pibrentasvir than the Q24K/L28M/R30Q/A92K RASs. Furthermore, a combination of pibrentasvir and sofosbuvir showed therapeutic efficacy against these RASs. Combination regimens may eradicate HCV with NS5A Q24K/L28M/R30E/A92K RASs.

Indexed as

Antiviral AgentsBenzimidazolesDrug Resistance, ViralHepacivirusImidazolesViral Nonstructural ProteinsBenzofuransBenzopyransCarbamatesFluorenesGenotypeHeterocyclic Compounds, 4 or More RingsHumansPyrazinesPyrrolidinesRepliconAntiviral AgentsBenzimidazolesBenzofuransBenzopyransCarbamatesdaclatasvirelbasvirFluorenesHeterocyclic Compounds, 4 or More RingsImidazolesledipasvirNS-5 protein, hepatitis C viruspibrentasvirPyrazinesPyrrolidinesRNA-Dependent RNA PolymeraseSofosbuvirSulfonamidesValinevelpatasvirViral Nonstructural Proteins

Identifiers

PMID39013947
PMCPMC11252252

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.