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  Identification of a Zika NS2B epitope as a biomarker for severe clinical phenotypes

Löffler, F. F., Viana, I. F. T., Fischer, N., Coêlho, D. F., Silva, C. S., Purificação, A. F., et al. (2021). Identification of a Zika NS2B epitope as a biomarker for severe clinical phenotypes. RSC Medicinal Chemistry, 12(9), 1525-1539. doi:10.1039/D1MD00124H.

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 Creators:
Löffler, Felix F.1, Author              
Viana, Isabelle F. T., Author
Fischer, Nico, Author
Coêlho, Danilo F., Author
Silva, Carolina S., Author
Purificação, Antônio F., Author
Araújo, Catarina M. C. S., Author
Leite, Bruno H. S., Author
Durães-Carvalho, Ricardo, Author
Magalhães, Tereza, Author
Morais, Clarice N. L., Author
Cordeiro, Marli T., Author
Lins, Roberto D., Author
Marques, Ernesto T. A., Author
Jaenisch, Thomas, Author
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1Felix Löffler, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_2385692              

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 Abstract: The identification of specific biomarkers for Zika infection and its clinical complications is fundamental to mitigate the infection spread, which has been associated with a broad range of neurological sequelae. We present the characterization of antibody responses in serum samples from individuals infected with Zika, presenting non-severe (classical) and severe (neurological disease) phenotypes, with high-density peptide arrays comprising the Zika NS1 and NS2B proteins. The data pinpoints one strongly IgG-targeted NS2B epitope in non-severe infections, which is absent in Zika patients, where infection progressed to the severe phenotype. This differential IgG profile between the studied groups was confirmed by multivariate data analysis. Molecular dynamics simulations and circular dichroism have shown that the peptide in solution presents itself in a sub-optimal conformation for antibody recognition, which led us to computationally engineer an artificial protein able to stabilize the NS2B epitope structure. The engineered protein was used to interrogate paired samples from mothers and their babies presenting Zika-associated microcephaly and confirmed the absence of NS2B IgG response in those samples. These findings suggest that the assessment of antibody responses to the herein identified NS2B epitope is a strong candidate biomarker for the diagnosis and prognosis of Zika-associated neurological disease.

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Language(s): eng - English
 Dates: 2021-07-052021
 Publication Status: Published in print
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Title: RSC Medicinal Chemistry
  Abbreviation : RSC Med. Chem.
Source Genre: Journal
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Publ. Info: Cambridge : Royal Socitey of Chemistry (RSC)
Pages: - Volume / Issue: 12 (9) Sequence Number: - Start / End Page: 1525 - 1539 Identifier: ISSN: 2040-2511

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Title: ChemRxiv : the Preprint Server for Chemistry
Source Genre: Journal
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Publ. Info: Washington, Frankfurt am Main, Cambridge : ACS, GCDh, RSC
Pages: - Volume / Issue: - Sequence Number: 141700439 Start / End Page: - Identifier: ZDB: 2949094-7