ArticleAntimicrobial agents and chemotherapy2015
In silico-based high-throughput screen for discovery of novel combinations for tuberculosis treatment.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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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.
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.
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Who cites it
7 citing papers in PubMed, 9 citations in OpenAlex.
- Synergism in drug combination of new tuberculosis antibiotics for drug-resistantMicrobiology spectrum · 2026Article
- Wollamide Cyclic Hexapeptides Synergize with Established and New Tuberculosis Antibiotics in Targeting Mycobacterium tuberculosis.Microbiology spectrum · 2023Article
- Advances in the design of combination therapies for the treatment of tuberculosis.Expert opinion on drug discovery · 2023Review
- Article
- A novel series of enoyl reductase inhibitors targeting the ESKAPE pathogens, Staphylococcus aureus and Acinetobacter baumannii.Bioorganic & medicinal chemistry · 2018Article
- Chemogenomics and orthology-based design of antibiotic combination therapies.Molecular systems biology · 2016Article
- Article
Corrections and comments
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Authors and funding
19 authors at 2 institutions in 1 country.
Funding
Abstract
There are currently 18 drug classes for the treatment of tuberculosis, including those in the development pipeline. An in silico simulation enabled combing the innumerably large search space to derive multidrug combinations. Through the use of ordinary differential equations (ODE), we constructed an in silico kinetic platform in which the major metabolic pathways in Mycobacterium tuberculosis and the mechanisms of the antituberculosis drugs were integrated into a virtual proteome. The optimized model was used to evaluate 816 triplets from the set of 18 drugs. The experimentally derived cumulative fractional inhibitory concentration (∑FIC) value was within twofold of the model prediction. Bacterial enumeration revealed that a significant number of combinations that were synergistic for growth inhibition were also synergistic for bactericidal effect. The in silico-based screen provided new starting points for testing in a mouse model of tuberculosis, in which two novel triplets and five novel quartets were significantly superior to the reference drug triplet of isoniazid, rifampin, and ethambutol (HRE) or the quartet of HRE plus pyrazinamide (HREZ).
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Registered trials
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.