ArticleAntimicrobial agents and chemotherapy2009
Target analysis of the experimental measles therapeutic AS-136A.
Article in Antimicrobial agents and chemotherapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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.
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.
Who cites it
27 citing papers in PubMed.
- Efficient and reliable measles reprogramming platform for the generation of human iPSC.Molecular therapy. Advances · 2026Article
- Structural insights into measles virus RNA synthesis regulation and pan-paramyxoviral polymerase inhibition by ERDRP-0519.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Serial Adaptation of Viruses for Reduced Susceptibility Profiling.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Structural basis of paramyxo- and pneumovirus polymerase inhibition by non-nucleoside small-molecule antivirals.Antimicrobial agents and chemotherapy · 2024Review
- Repurposing an In Vitro Measles Virus Dissemination Assay for Screening of Antiviral Compounds.Viruses · 2022Review
- Small-molecule polymerase inhibitor protects non-human primates from measles and reduces shedding.Nature communications · 2021Article
- Recent advances in the discovery of potent RNA-dependent RNA-polymerase (RdRp) inhibitors targeting viruses.RSC medicinal chemistry · 2021Review
- Therapeutic targeting of measles virus polymerase with ERDRP-0519 suppresses all RNA synthesis activity.PLoS pathogens · 2021Article
- Advances in Antiviral Therapy for Subacute Sclerosing Panencephalitis.Molecules (Basel, Switzerland) · 2021Review
- Nuphar lutea Extracts Exhibit Anti-Viral Activity against the Measles Virus.Molecules (Basel, Switzerland) · 2020Article
- Measles Resurgence and Drug Development.Current opinion in virology · 2020Review
- Measles Encephalitis: Towards New Therapeutics.Viruses · 2019Review
- Polymerases of paramyxoviruses and pneumoviruses.Virus research · 2017Review
- Organization, Function, and Therapeutic Targeting of the Morbillivirus RNA-Dependent RNA Polymerase Complex.Viruses · 2016Review
- Structure-guided design of small-molecule therapeutics against RSV disease.Expert opinion on drug discovery · 2016Article
- Article
- A pioneering countermeasure against measles virus.Annals of translational medicine · 2015Article
- The paramyxovirus polymerase complex as a target for next-generation anti-paramyxovirus therapeutics.Frontiers in microbiology · 2015Review
- An orally available, small-molecule polymerase inhibitor shows efficacy against a lethal morbillivirus infection in a large animal model.Science translational medicine · 2014Article
- Synergizing vaccinations with therapeutics for measles eradication.Expert opinion on drug discovery · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
Abstract
No effective therapeutic is currently in place for improved case management of severe measles or the rapid control of outbreaks. Through high-throughput screening, we recently identified a novel small-molecule class that potently blocks activity of the measles virus (MeV) RNA-dependent RNA polymerase (RdRp) complex in transient replicon assays. However, the nature of the block in RdRp activity and the physical target of the compound remained elusive. Through real-time reverse transcription-PCR analysis, we demonstrate that the lead compound AS-136A blocks viral RNA synthesis in the context of an infection. Adaptation of different MeV strains to growth in the presence of the compound identified three candidate hot spots for resistance that are located in conserved domains of the viral polymerase (L protein) subunit of the RdRp complex. Rebuilding of individual mutations in RdRp-driven reporter assays and recombinant MeV traced the molecular basis for resistance to specific mutations in L. Mutations responsible for resistance cluster in the immediate vicinity of the proposed catalytic center for phosphodiester bond formation and neighboring conserved domains of L, providing support for effective inhibition of a paramyxovirus RdRp complex through interaction of a nonnucleoside small-molecule inhibitor with the L protein. Resistance mutations are located in regions of L that are fully conserved among viral isolates, and recombinant MeV harboring individual resistance mutations show some delay in the onset of viral growth in vitro. Taken together, these data support the hypothesis that acquiring mutations in these L domains may reduce virus fitness.
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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.