Insights into the ZIKV NS1 Virology from Different Strains through a Fine Analysis of Physicochemical Properties

Sergio A Poveda-Cuevas; Catherine Etchebest; Fernando L Barroso da Silva

doi:10.1021/acsomega.8b02081

Insights into the ZIKV NS1 Virology from Different Strains through a Fine Analysis of Physicochemical Properties

ACS Omega. 2018 Nov 29;3(11):16212-16229. doi: 10.1021/acsomega.8b02081. eCollection 2018 Nov 30.

Authors

Sergio A Poveda-Cuevas^{1

2

3}, Catherine Etchebest^{4

5

6

3}, Fernando L Barroso da Silva^{1

2

3

7}

Affiliations

¹ Programa Interunidades em Bioinformática, Universidade de São Paulo, São Paulo 05508-090, Brazil.
² Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo 14040-903, Brazil.
³ University of São Paulo and Université Sorbonne Paris Cité Joint International Laboratory in Structural Bioinformatics.
⁴ Institut National de la Transfusion Sanguine, Paris 75015, France.
⁵ Biologie Intégrée du Globule Rouge, Equipe 2, Dynamique des Structures et des Interactions Moléculaires, Institut National de la Santé et de la Recherche Médicale, UMR_S 1134, Paris 75015, France.
⁶ Université Sorbonne Paris Cité and Université Paris Diderot, 75013 Paris, France.
⁷ Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, North Carolina 27606, United States.

Abstract

The flavivirus genus has several organisms responsible for generating various diseases in humans. Recently, especially in tropical regions, Zika virus (ZIKV) has raised great health concerns due to the high number of cases affecting the area during the last years that has been accompanied by a rise in the cases of the Guillain-Barré syndrome and fetal and neonatal microcephaly. Diagnosis is still difficult since the clinical symptoms between ZIKV and other flaviviruses (e.g., dengue and yellow fever) are highly similar. The understanding of their common physicochemical properties that are pH-dependent and biomolecular interaction features and their differences sheds light on the relation strain-virulence and might suggest alternative strategies toward differential serological diagnostics and therapeutic intervention. Due to their immunogenicity, the primary focus of this study was on the ZIKV nonstructural proteins 1 (NS1). By means of computational studies and semiquantitative theoretical analyses, we calculated the main physicochemical properties of this protein from different strains that are directly responsible for the biomolecular interactions and, therefore, can be related to the differential infectivity of the strains. We also mapped the electrostatic differences at both the sequence and structural levels for the strains from Uganda to Brazil, which could suggest possible molecular mechanisms for the increase of the virulence of ZIKV in Brazil. Exploring the interfaces used by NS1 to self-associate in some different oligomeric states and interact with membranes and the antibody, we could map the strategy used by the ZIKV during its evolutionary process. This indicates possible molecular mechanisms that can be correlated with the different immunological responses. By comparing with the known antibody structure available for the West Nile virus, we demonstrated that this antibody would have difficulties to neutralize the NS1 from the Brazilian strain. The present study also opens up perspectives to computationally design high-specificity antibodies.