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bioRxiv · 10.1101/2022.04.08.487413

NS1 from Two Zika Virus Strains Differently Interact with a Membrane: A Plausible Explanation for their Differential Virulence

Poveda Cuevas, S. A.·Barroso da Silva, F. L.·Etchebest, C.
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Abstract

Zika virus (ZIKV) from Uganda (UG) expresses a phenotype related to fetal loss whereas the variant from Brazil (BR) induces microcephaly in neonates. The differential virulence has a direct relation to biomolecular mechanisms that make one strain more aggressive than the other. The non-structural protein 1 (NS1) is a key viral toxin to comprehend these viral discrepancies because of its versatility in many processes of the virus life cycle. Here, we aim to examine through coarse-grained models and molecular dynamics simulations the protein-membrane interactions for both NS1ZIKV-UG and NS1ZIKV-BR dimers. A first evaluation allowed us to establish that the NS1 proteins, in the membrane presence, explore new conformational spaces when compared to systems simulated without a lipid bilayer. These events derive from both differential coupling patterns and discrepant binding affinities to the membrane. The N-terminal domain, intertwined loop, and greasy finger proposed previously as binding membrane regions were also computationally confirmed by us. The anchoring sites have aromatic and ionizable residues that manage the assembly of NS1 toward the membrane, especially for the Ugandan variant. Furthermore, the protein-membrane interaction induces perturbation in the distal part related to putative epitopes. These results open up new strategies for the treatment of flaviviruses. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=75 SRC="FIGDIR/small/487413v1_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@11023e9org.highwire.dtl.DTLVardef@a5d417org.highwire.dtl.DTLVardef@1073b91org.highwire.dtl.DTLVardef@1d7cffe_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Poveda Cuevas, S. A., Barroso da Silva, F. L., Etchebest, C.. 2022-04-10. NS1 from Two Zika Virus Strains Differently Interact with a Membrane: A Plausible Explanation for their Differential Virulence. https://doi.org/10.1101/2022.04.08.487413

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