Protein-Protein Interaction-Guided Peptides Interfere with Early Zika Virus Entry-Associated Events.
- 1Molecular Biology and Virology Laboratory, Faculty of Medicine and Health Sciences, Corporación Universitaria Empresarial Alexander von Humboldt, Armenia 630003, Quindío, Colombia.
- 2Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Abstract
Zika virus (ZIKV) remains a public health concern because of its association with neurological complications and congenital disease, yet no specific antiviral therapy has been approved. Since the envelope (E) protein mediates viral attachment and early entry-associated membrane events, it represents an attractive antiviral target. Here, we used a protein-protein interaction-guided strategy to design peptides to interfere with predicted interfaces between the ZIKV E protein and cellular receptors involved in attachment. After in silico filtering and preliminary screening, six peptides (PZ1-PZ6) were selected. These peptides showed heterogeneous physicochemical profiles, low cytotoxicity and hemolytic activity under the tested conditions, and docking-predicted interactions with functional E protein regions. In HTR-8/SVneo cells, antiviral activity depended on the timing of exposure, with greater reductions in infectious titers during co-treatment and post-treatment. All peptides also reduced titers in anti-adsorption assays, supporting interference with viral attachment or early entry-associated events. Consistently, DiOC18 fluorescence signals were reduced in a peptide-specific manner, particularly for PZ3 and PZ6. Nuclease protection assays showed no extensive exposure of the viral genome, whereas transmission electron microscopy revealed ultrastructural alterations without generalized particle disruption. Overall, PZ1-PZ6 are promising protein-protein interaction-guided anti-ZIKV peptide candidates with activity against early viral entry-associated events.
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BibTeX
@article{rodriguezsalazar2026proteinprotein,
title = {{Protein-Protein Interaction-Guided Peptides Interfere with Early Zika Virus Entry-Associated Events.}},
author = {Carlos Andres Rodríguez-Salazar and Delia Piedad Recalde-Reyes and Santiago Linares-Jiménez and Carolina López-Cardoso and María Isabel Giraldo},
journal = {Viruses},
year = {2026},
month = sep,
doi = {10.3390/v18101066},
url = {https://europepmc.org/article/MED/42943986},
note = {CC BY},
}
RIS
TY - JOUR
TI - Protein-Protein Interaction-Guided Peptides Interfere with Early Zika Virus Entry-Associated Events.
AU - Carlos Andres Rodríguez-Salazar
AU - Delia Piedad Recalde-Reyes
AU - Santiago Linares-Jiménez
AU - Carolina López-Cardoso
AU - María Isabel Giraldo
PY - 2026
DA - 2026/09/25
JO - Viruses
DO - 10.3390/v18101066
UR - https://europepmc.org/article/MED/42943986
AB - Zika virus (ZIKV) remains a public health concern because of its association with neurological complications and congenital disease, yet no specific antiviral therapy has been approved. Since the envelope (E) protein mediates viral attachment and early entry-associated membrane events, it represents an attractive antiviral target. Here, we used a protein-protein interaction-guided strategy to design peptides to interfere with predicted interfaces between the ZIKV E protein and cellular receptors involved in attachment. After in silico filtering and preliminary screening, six peptides (PZ1-PZ6) were selected. These peptides showed heterogeneous physicochemical profiles, low cytotoxicity and hemolytic activity under the tested conditions, and docking-predicted interactions with functional E protein regions. In HTR-8/SVneo cells, antiviral activity depended on the timing of exposure, with greater reductions in infectious titers during co-treatment and post-treatment. All peptides also reduced titers in anti-adsorption assays, supporting interference with viral attachment or early entry-associated events. Consistently, DiOC18 fluorescence signals were reduced in a peptide-specific manner, particularly for PZ3 and PZ6. Nuclease protection assays showed no extensive exposure of the viral genome, whereas transmission electron microscopy revealed ultrastructural alterations without generalized particle disruption. Overall, PZ1-PZ6 are promising protein-protein interaction-guided anti-ZIKV peptide candidates with activity against early viral entry-associated events.
SN - 1999-4915
ER -