Evidence map›Paper›PMID 32907977›Full record

ArticleJournal of virology2020

Two RNA Tunnel Inhibitors Bind in Highly Conserved Sites in Dengue Virus NS5 Polymerase: Structural and Functional Studies.

Rishi Arora, Chong Wai Liew, Tingjin Sherryl Soh, Dorcas Adobea Otoo, Cheah Chen Seh, Kimberley Yue, Shahul Nilar, Gang Wang, Fumiaki Yokokawa, Christian G Noble and 6 more

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
3.6field-weighted citation impact, top 6% 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

20 citing papers in PubMed, 30 citations in OpenAlex.

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  15. Structure-first identification of RNA elements that regulate dengue virus genome architecture and replication.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  16. Article
  17. Article
  18. Review
  19. Virus structure and structure-based antivirals.Current opinion in virology · 2021
    Review
  20. 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

16 authors at 3 institutions in 2 countries.

Rishi AroraNovartis Institute for Biomedical Research, Cambridge, Massachusetts, USA.
Chong Wai LiewNTU Institute of Structural Biology, Nanyang Technological University, Singapore.
Tingjin Sherryl SohNovartis Institute for Tropical Diseases, Singapore.
Dorcas Adobea OtooNovartis Institute for Tropical Diseases, Singapore.
Cheah Chen SehNovartis Institute for Tropical Diseases, Singapore.
Kimberley YueNovartis Institute for Biomedical Research, Cambridge, Massachusetts, USA.
Shahul NilarNovartis Institute for Tropical Diseases, Singapore.
Gang WangNovartis Institute for Tropical Diseases, Singapore.
Fumiaki YokokawaNovartis Institute for Tropical Diseases, Singapore.
Christian G NobleNovartis Institute for Tropical Diseases, Singapore.
Yen Liang ChenNovartis Institute for Tropical Diseases, Singapore.ORCID 0000-0002-0121-5658
Pei-Yong ShiNovartis Institute for Tropical Diseases, Singapore.
Julien LescarNTU Institute of Structural Biology, Nanyang Technological University, Singapore.
Thomas M SmithNovartis Institute for Biomedical Research, Cambridge, Massachusetts, USA.
Timothy E BensonNovartis Institute for Biomedical Research, Cambridge, Massachusetts, USA timothy.benson@novartis.com siewpheng-lim@denka.com.sg.
Siew Pheng LimNovartis Institute for Tropical Diseases, Singapore timothy.benson@novartis.com siewpheng-lim@denka.com.sg.ORCID 0000-0002-7377-5662
Novartis (Singapore) · SGNovartis (United States) · USNanyang Technological University · SG

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Dengue virus (DENV) NS5 RNA-dependent RNA polymerase (RdRp), an important drug target, synthesizes viral RNA and is essential for viral replication. While a number of allosteric inhibitors have been reported for hepatitis C virus RdRp, few have been described for DENV RdRp. Following a diverse compound screening campaign and a rigorous hit-to-lead flowchart combining biochemical and biophysical approaches, two DENV RdRp nonnucleoside inhibitors were identified and characterized. These inhibitors show low- to high-micromolar inhibition in DENV RNA polymerization and cell-based assays. X-ray crystallography reveals that they bind in the enzyme RNA template tunnel. One compound (NITD-434) induced an allosteric pocket at the junction of the fingers and palm subdomains by displacing residue V603 in motif B. Binding of another compound (NITD-640) ordered the fingers loop preceding the F motif, close to the RNA template entrance. Most of the amino acid residues that interacted with these compounds are highly conserved in flaviviruses. Both sites are important for polymerase

Indexed as

Allosteric SiteAntiviral AgentsBinding SitesCrystallography, X-RayDengueDengue VirusHigh-Throughput Screening AssaysHIV Reverse TranscriptaseHumansModels, MolecularRepliconRNA-Dependent RNA PolymeraseSequence AlignmentSequence Analysis, ProteinViral Nonstructural ProteinsVirus ReplicationAntiviral AgentsHIV Reverse TranscriptaseNS5 protein, dengue virusreverse transcriptase, Human immunodeficiency virus 1RNA-Dependent RNA PolymeraseViral Nonstructural Proteinsbinding sitedengue virusflaviviruseshigh-throughput screeninginhibitornonstructural proteinRNA-dependent RNA polymeraseSPRX-ray crystallography

Identifiers

PMID32907977
PMCPMC7925201
OpenAlexW3083146590

What OpenQuestion holds

Textmetadata
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.