Evidence map›Paper›PMID 35269938›Full record

ArticleInternational journal of molecular sciences2022

Identification of Kukoamine A, Zeaxanthin, and Clexane as New Furin Inhibitors.

David Zaragoza-Huesca, Carlos Martínez-Cortés, Antonio Jesús Banegas-Luna, Alfonso Pérez-Garrido, Josefina María Vegara-Meseguer, Julia Peñas-Martínez, Maria Carmen Rodenas, Salvador Espín, Horacio Pérez-Sánchez, Irene Martínez-Martínez

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.8field-weighted citation impact, top 16% 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

5 citing papers in PubMed, 10 citations in OpenAlex.

  1. Review
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  4. Article
  5. 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

10 authors at 2 institutions in 1 country.

David Zaragoza-HuescaServicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, CIBERER, Universidad de Murcia, IMIB-Arrixaca, 30003 Murcia, Spain.ORCID 0000-0001-7330-7597
Carlos Martínez-CortésStructural Bioinformatics and High Performance Computing Research Group (BIO-HPC), Computer Engineering Department, UCAM Universidad Católica de Murcia, 30107 Guadalupe, Spain.
Antonio Jesús Banegas-LunaStructural Bioinformatics and High Performance Computing Research Group (BIO-HPC), Computer Engineering Department, UCAM Universidad Católica de Murcia, 30107 Guadalupe, Spain.
Alfonso Pérez-GarridoStructural Bioinformatics and High Performance Computing Research Group (BIO-HPC), Computer Engineering Department, UCAM Universidad Católica de Murcia, 30107 Guadalupe, Spain.
Josefina María Vegara-MeseguerStructural Bioinformatics and High Performance Computing Research Group (BIO-HPC), Computer Engineering Department, UCAM Universidad Católica de Murcia, 30107 Guadalupe, Spain.
Julia Peñas-MartínezServicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, CIBERER, Universidad de Murcia, IMIB-Arrixaca, 30003 Murcia, Spain.
Maria Carmen RodenasServicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, CIBERER, Universidad de Murcia, IMIB-Arrixaca, 30003 Murcia, Spain.
Salvador EspínServicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, CIBERER, Universidad de Murcia, IMIB-Arrixaca, 30003 Murcia, Spain.
Horacio Pérez-SánchezStructural Bioinformatics and High Performance Computing Research Group (BIO-HPC), Computer Engineering Department, UCAM Universidad Católica de Murcia, 30107 Guadalupe, Spain.ORCID 0000-0003-4468-7898
Irene Martínez-MartínezServicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, CIBERER, Universidad de Murcia, IMIB-Arrixaca, 30003 Murcia, Spain.ORCID 0000-0002-1067-6464
Centro Regional de Hemodonación · ESUniversidad Católica de Murcia · ES

Funding

Fundación Seneca Project 00002/COVI/20Universidad Católica San Antonio de Murcia FURINHICOVID
6 · The paper itself

Abstract

The endogenous protease furin is a key protein in many different diseases, such as cancer and infections. For this reason, a wide range of studies has focused on targeting furin from a therapeutic point of view. Our main objective consisted of identifying new compounds that could enlarge the furin inhibitor arsenal; secondarily, we assayed their adjuvant effect in combination with a known furin inhibitor, CMK, which avoids the SARS-CoV-2 S protein cleavage by means of that inhibition. Virtual screening was carried out to identify potential furin inhibitors. The inhibition of physiological and purified recombinant furin by screening selected compounds, Clexane, and these drugs in combination with CMK was assayed in fluorogenic tests by using a specific furin substrate. The effects of the selected inhibitors from virtual screening on cell viability (293T HEK cell line) were assayed by means of flow cytometry. Through virtual screening, Zeaxanthin and Kukoamine A were selected as the main potential furin inhibitors. In fluorogenic assays, these two compounds and Clexane inhibited both physiological and recombinant furin in a dose-dependent way. In addition, these compounds increased physiological furin inhibition by CMK, showing an adjuvant effect. In conclusion, we identified Kukoamine A, Zeaxanthin, and Clexane as new furin inhibitors. In addition, these drugs were able to increase furin inhibition by CMK, so they could also increase its efficiency when avoiding S protein proteolysis, which is essential for SARS-CoV-2 cell infection.

Indexed as

Amino Acid Chloromethyl KetonesCatalytic DomainCell Line, TumorCell SurvivalCOVID-19EnoxaparinFurinHEK293 CellsHumansMolecular Docking SimulationMolecular StructureProtease InhibitorsProteolysisSARS-CoV-2SpermineSpike Glycoprotein, CoronavirusAmino Acid Chloromethyl KetonesdecanoylRVKRchloromethylketoneEnoxaparinFurinkukoamine AProtease InhibitorsSpermineSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2ZeaxanthinsCMKfurininhibitorsvirtual screening

Identifiers

PMID35269938
PMCPMC8911046
OpenAlexW4214853348

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.