Evidence map›Paper›PMID 34894959›Full record

ArticleJournal of enzyme inhibition and medicinal chemistry2022

Searching for drug leads targeted to the hydrophobic cleft of dengue virus capsid protein.

Liliane O Ortlieb, Ícaro P Caruso, Nathane C Mebus-Antunes, Andrea T Da Poian, Elaine da C Petronilho, José Daniel Figueroa-Villar, Claudia J Nascimento, Fabio C L Almeida

Open access · goldAbstract read
In one paragraph

Article in Journal of enzyme inhibition and medicinal chemistry, 2022. 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
0.4field-weighted citation impact, top 32% 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

3 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
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

8 authors at 3 institutions in 1 country.

Liliane O OrtliebDepartment of Chemistry, Military Institute of Engineering (IME), Rio de Janeiro, Brazil.
Ícaro P CarusoInstitute of Medical Biochemistry Leopoldo de Meis (IBqM) and National Center for Structural Biology and Bioimaging (CENABIO), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil.ORCID 0000-0003-4464-0520
Nathane C Mebus-AntunesInstitute of Medical Biochemistry Leopoldo de Meis (IBqM), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil.
Andrea T Da PoianInstitute of Medical Biochemistry Leopoldo de Meis (IBqM), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil.
Elaine da C PetronilhoDepartment of Chemistry, Military Institute of Engineering (IME), Rio de Janeiro, Brazil.
José Daniel Figueroa-VillarDepartment of Chemistry, Military Institute of Engineering (IME), Rio de Janeiro, Brazil.
Claudia J NascimentoDepartment of Natural Sciences, Institute of Biosciences, Federal University of the State of Rio de Janeiro (UNIRIO), Rio de Janeiro, Brazil.
Fabio C L AlmeidaInstitute of Medical Biochemistry Leopoldo de Meis (IBqM) and National Center for Structural Biology and Bioimaging (CENABIO), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil.ORCID 0000-0001-6046-7006
Universidade Federal do Rio de Janeiro · BRMilitary Institute of Engineering · BRUniversidade Federal do Estado do Rio de Janeiro · BR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

We synthesised and screened 18 aromatic derivatives of guanylhydrazones and oximes aromatic for their capacity to bind to dengue virus capsid protein (DENVC). The intended therapeutic target was the hydrophobic cleft of DENVC, which is a region responsible for its anchoring in lipid droplets in the infected cells. The inhibition of this process completely suppresses virus infectivity. Using NMR, we describe five compounds able to bind to the α1-α2 interface in the hydrophobic cleft. Saturation transfer difference experiments showed that the aromatic protons of the ligands are important for the interaction with DENVC. Fluorescence binding isotherms indicated that the selected compounds bind at micromolar affinities, possibly leading to binding-induced conformational changes. NMR-derived docking calculations of ligands showed that they position similarly in the hydrophobic cleft. Cytotoxicity experiments and calculations of

Indexed as

Antiviral AgentsCapsid ProteinsDengue VirusDose-Response Relationship, DrugHydrazonesHydrophobic and Hydrophilic InteractionsMicrobial Sensitivity TestsMolecular StructureOximesStructure-Activity RelationshipAntiviral AgentsCapsid ProteinsHydrazonesOximesDengue virusDENVCdrug-ligand interactionfluorescenceNMR

Identifiers

PMID34894959
PMCPMC8667904
OpenAlexW4200107390

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.