A diarylamine derived from anthranilic acid inhibits ZIKV replication.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
27 11 2019
Historique:
received: 25 01 2019
accepted: 29 10 2019
entrez: 29 11 2019
pubmed: 30 11 2019
medline: 4 11 2020
Statut: epublish

Résumé

Zika virus (ZIKV) is a mosquito-transmitted Flavivirus, originally identified in Uganda in 1947 and recently associated with a large outbreak in South America. Despite extensive efforts there are currently no approved antiviral compounds for treatment of ZIKV infection. Here we describe the antiviral activity of diarylamines derived from anthranilic acid (FAMs) against ZIKV. A synthetic FAM (E3) demonstrated anti-ZIKV potential by reducing viral replication up to 86%. We analyzed the possible mechanisms of action of FAM E3 by evaluating the intercalation of this compound into the viral dsRNA and its interaction with the RNA polymerase of bacteriophage SP6. However, FAM E3 did not act by these mechanisms. In silico results predicted that FAM E3 might bind to the ZIKV NS3 helicase suggesting that this protein could be one possible target of this compound. To test this, the thermal stability and the ATPase activity of the ZIKV NS3 helicase domain (NS3

Identifiants

pubmed: 31776405
doi: 10.1038/s41598-019-54169-z
pii: 10.1038/s41598-019-54169-z
pmc: PMC6881388
doi:

Substances chimiques

Amines 0
Antiviral Agents 0
Viral Proteins 0
ortho-Aminobenzoates 0
anthranilic acid 0YS975XI6W
NS3 protein, zika virus EC 3.4.-
Serine Endopeptidases EC 3.4.21.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

17703

Subventions

Organisme : Wellcome Trust
ID : 096670
Pays : United Kingdom

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Auteurs

Suely Silva (S)

Laboratory of Virology, Institute of Biomedical Science, ICBIM, Federal University of Uberlandia, Uberlândia, MG, Brazil.
São Paulo State University, IBILCE, S. José do Rio Preto, SP, Brazil.

Jacqueline Farinha Shimizu (JF)

Laboratory of Virology, Institute of Biomedical Science, ICBIM, Federal University of Uberlandia, Uberlândia, MG, Brazil.
São Paulo State University, IBILCE, S. José do Rio Preto, SP, Brazil.

Débora Moraes de Oliveira (DM)

Laboratory of Virology, Institute of Biomedical Science, ICBIM, Federal University of Uberlandia, Uberlândia, MG, Brazil.

Leticia Ribeiro de Assis (LR)

Laboratory of Antibiotics and Chemotherapeutics, São Paulo State University, IBILCE, S. José do Rio Preto, SP, Brazil.

Cintia Bittar (C)

São Paulo State University, IBILCE, S. José do Rio Preto, SP, Brazil.

Melina Mottin (M)

LabMol - Laboratory of Molecular Modeling and Drug Design, Faculdade de Farmácia, Universidade Federal de Goias, Goiânia, GO, 74605- 170, Brazil.

Bruna Katiele de Paula Sousa (BKP)

LabMol - Laboratory of Molecular Modeling and Drug Design, Faculdade de Farmácia, Universidade Federal de Goias, Goiânia, GO, 74605- 170, Brazil.

Nathalya Cristina de Moraes Roso Mesquita (NCMR)

Institute of Physics of São Carlos, University of São Paulo, São Carlos, Brazil.

Luis Octávio Regasini (LO)

Laboratory of Antibiotics and Chemotherapeutics, São Paulo State University, IBILCE, S. José do Rio Preto, SP, Brazil.

Paula Rahal (P)

São Paulo State University, IBILCE, S. José do Rio Preto, SP, Brazil.

Glaucius Oliva (G)

Institute of Physics of São Carlos, University of São Paulo, São Carlos, Brazil.

Alexander Luke Perryman (AL)

Department of Pharmacology, Physiology and Neuroscience, Rutgers University-New Jersey Medical School, Newark, NJ 07103, United States.
Repare Therapeutics, 7210 Rue Frederick-Banting, Suite 100, Montreal, QC, H4S 2A1, Canada.

Sean Ekins (S)

Collaborations Pharmaceuticals, Inc., 840 Main Campus Drive, Lab 3510, Raleigh, NC, 27606, United States.

Carolina Horta Andrade (CH)

LabMol - Laboratory of Molecular Modeling and Drug Design, Faculdade de Farmácia, Universidade Federal de Goias, Goiânia, GO, 74605- 170, Brazil.

Luiz Ricardo Goulart (LR)

Laboratory of Nanobiotechnology, Federal University of Uberlandia, Uberlândia, MG, Brasil.

Robinson Sabino-Silva (R)

Integrative Physiology and Salivary Nanobiotechnology Group, Federal University of Uberlandia, Uberlândia, MG, Brasil.

Andres Merits (A)

Institute of Technology, University of Tartu, Nooruse 1, 50411, Tartu, Estonia.

Mark Harris (M)

School of Molecular and Cellular Biology, Faculty of Biological Sciences and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, United Kingdom.

Ana Carolina Gomes Jardim (ACG)

Laboratory of Virology, Institute of Biomedical Science, ICBIM, Federal University of Uberlandia, Uberlândia, MG, Brazil. jardim@ufu.br.
São Paulo State University, IBILCE, S. José do Rio Preto, SP, Brazil. jardim@ufu.br.

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