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Synthetic rational design of live-attenuated Zika viruses based on a computational model.
Nucleic Acids Res
January 2025
SynVaccine Ltd, Ramat Hachayal, 3 Golda Meir Street, Science Park, Nes Ziona 7403648, Israel.
Many viruses of the Flaviviridae family, including the Zika virus (ZIKV), are human pathogens of significant public health concerns. Despite extensive research, there are currently no approved vaccines available for ZIKV and specifically no live-attenuated Zika vaccine. In this current study, we suggest a novel computational algorithm for generating live-attenuated vaccines via the introduction of silent mutation into regions that undergo selection for strong or weak local RNA folding or into regions that exhibit medium levels of sequence conservation.
View Article and Find Full Text PDFComparison of Three Chimeric Zika Vaccine Prototypes Developed on the Genetic Background of the Clinically Proven Live-Attenuated Japanese Encephalitis Vaccine SA-14-2.
Int J Mol Sci
December 2024
Department of Animal Dairy and Veterinary Sciences, College of Agriculture and Applied Sciences, Utah State University, Logan, UT 84322, USA.
Zika virus (ZIKV) is a medically important mosquito-borne orthoflavivirus, but no vaccines are currently available to prevent ZIKV-associated disease. In this study, we compared three recombinant chimeric viruses developed as candidate vaccine prototypes (rJEV/ZIKV, rJEV/ZIKV, and rJEV/ZIKV), in which the two neutralizing antibody-inducing prM and E genes from each of three genetically distinct ZIKV strains were used to replace the corresponding genes of the clinically proven live-attenuated Japanese encephalitis virus vaccine SA-14-2 (rJEV). In WHO-certified Vero cells (a cell line suitable for vaccine production), rJEV/ZIKV exhibited the slowest viral growth, formed the smallest plaques, and displayed a unique protein expression profile with the highest ratio of prM to cleaved M when compared to the other two chimeric viruses, rJEV/ZIKV and rJEV/ZIKV, as well as their vector, rJEV.
View Article and Find Full Text PDFAn Overview of Zika Virus and Zika Virus Induced Neuropathies.
Int J Mol Sci
December 2024
Department of Entomology, Pennsylvania State University, University Park, PA 16802, USA.
Flaviviruses pose a major public health concern across the globe. Among them, Zika virus (ZIKV) is an emerging and reemerging arthropod-borne flavivirus that has become a major international public health problem following multiple large outbreaks over the past two decades. The majority of infections caused by ZIKV exhibit mild symptoms.
View Article and Find Full Text PDFSynthesis and Antiviral Evaluation of 5-(4-Aryl-1,3-butadiyn-1-yl)-uridines and Their Phosphoramidate Pronucleotides.
Molecules
December 2024
Institute of Organic and Analytical Chemistry (ICOA UMR 7311), CNRS, University of Orleans, F-45067 Orléans, France.
The emergence of RNA viruses driven by global population growth and international trade highlights the urgent need for effective antiviral agents that can inhibit viral replication. Nucleoside analogs, which mimic natural nucleotides, have shown promise in targeting RNA-dependent RNA polymerases (RdRps). Starting from protected 5-iodouridine, we report the synthesis of -substituted-(1,3-diyne)-uridines nucleosides and their phosphoramidate prodrugs.
View Article and Find Full Text PDFWe report a case of Zika virus (ZIKV) infection in a pregnant woman from Denmark who traveled to Thailand during her first trimester. Late in the second trimester, severe microcephaly was diagnosed in the fetus, and ZIKV infection was confirmed. Travelers and clinicians should be aware of ongoing ZIKV risk in Thailand.
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