Evidence map›Paper›PMID 29215062›Full record

ArticleScientific reports2017

Protein-Structure Assisted Optimization of 4,5-Dihydroxypyrimidine-6-Carboxamide Inhibitors of Influenza Virus Endonuclease.

Diane Beylkin, Gyanendra Kumar, Wei Zhou, Jaehyeon Park, Trushar Jeevan, Chandraiah Lagisetti, Rhodri Harfoot, Richard J Webby, Stephen W White, Thomas R Webb

Abstract read
In one paragraph

Article in Scientific reports, 2017. 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
–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

9 citing papers in PubMed, 10 citations in OpenAlex.

  1. Review
  2. Pharmacophores of Influenza Virus PA Endonuclease Inhibitors.Advances in experimental medicine and biology · 2026
    Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. 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

10 authors at 2 institutions in 1 country.

Diane BeylkinBioscience Division, SRI International, Menlo Park, CA, 94025, USA.
Gyanendra KumarDepartment of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.ORCID 0000-0001-7593-0737
Wei ZhouBioscience Division, SRI International, Menlo Park, CA, 94025, USA.
Jaehyeon ParkBioscience Division, SRI International, Menlo Park, CA, 94025, USA.
Trushar JeevanDepartment of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.
Chandraiah LagisettiBioscience Division, SRI International, Menlo Park, CA, 94025, USA.
Rhodri HarfootDepartment of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.
Richard J WebbyDepartment of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.
Stephen W WhiteDepartment of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.ORCID 0000-0001-8188-5944
Thomas R WebbBioscience Division, SRI International, Menlo Park, CA, 94025, USA. thomas.webb@sri.com.
SRI International · USSt. Jude Children's Research Hospital · US

Funding

Viral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI CHARLES ROBERTS · 1985 to 2026
$166.9M
Small molecule inhibitory leads against influenza RdRpR01AI098757 · NIAID · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI WEBB, THOMAS ROY · 2012 to 2016
$3.1M
NCI NIH HHS P30 CA021765NIAID NIH HHS R01 AI098757
6 · The paper itself

Abstract

Influenza is a serious hazard to human health that causes hundreds of thousands of deaths annually. Though vaccines and current therapeutics can blunt some of the perilous impact of this viral infection, new treatments are needed due to the constantly evolving nature of this virus. Recently, our growing understanding of an essential influenza viral protein, PA, has led to the development of focused libraries of new small molecules that specifically target the active site of the PA influenza endonuclease, which we report here. Our overarching approach has been to proactively develop lead inhibitors that are less likely to rapidly develop clinical resistance by optimizing inhibitors that retain activity against induced resistant mutants. Here, we report details behind the discovery of new potent inhibitors of wild type and resistant mutant endonucleases along with their high-resolution co-crystal structure-activity relationships. These results add to our understanding of nuclease protein targets and potentially serve as starting points for a new therapeutic approach to the treatment of influenza.

Indexed as

AmidesAntiviral AgentsCatalytic DomainCell ProliferationCrystallography, X-RayEndoribonucleasesEnzyme InhibitorsHumansInfluenza A Virus, H1N1 SubtypeInfluenza, HumanMolecular StructureProtein ConformationRNA-Dependent RNA PolymeraseStructure-Activity RelationshipViral ProteinsAmidesAntiviral AgentsEndoribonucleasesEnzyme InhibitorsPA protein, influenza virusesRNA-Dependent RNA PolymeraseViral Proteins

Identifiers

PMID29215062
PMCPMC5719402
OpenAlexW2773349758

What OpenQuestion holds

Textmetadata
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.