scholarly journals In Silico Approach To Design a B-cell Epitope Based Vaccine Target Against Yellow Fever Virus

2019 ◽  
Vol 35 (1) ◽  
pp. 27-35
Author(s):  
Shamira Tabrejee ◽  
M Mahboob Hossain
Keyword(s):  
Yellow Fever ◽  
Yellow Fever Virus ◽  
Peptide Vaccine ◽  
Cell Epitope ◽  
Epitope Prediction ◽  
Fever Virus ◽  
Young Infants ◽  
E Protein

Yellow fever virus is a prototype member of the Flaviviridae family causing high fever and jaundice. Though YF 17D vaccine is administered to yellow fever patients, however it can produce adverse effects in immunocompromised, older people and young infants. The aim of this study is to design an epitope-based peptide vaccine by targeting envelope (E) protein of Yellow Fever Virus. Thirty sequences of E protein of Yellow Fever Virus strains were retrieved from NCBI database. E protein was found to be mostly conserved among all the sequences with little variability and also was identified as a probable antigen. Different epitope prediction tools predicted 4 common epitopes, 3 of which were found to be antigenic. A peptide VKNPTDTGin E protein was predicted to have surface accessibility which overlaps with the VKNPTDTGHGT epitope.So, the whole VKNPTDTGHGT epitope was taken for further analysis. The VKNPTDTGHGT epitope showed 96.67% conservancy and also possesses flexibility, hydrophilicity and non-toxicity. Therefore, VKNPTDTGHGT can be regarded as a potential vaccine candidate against Yellow fever virus with further in vitro and in vivo validation. Bangladesh J Microbiol, Volume 35 Number 1 June 2018, pp 27-35

scholarly journals Yellow fever virus is susceptible to sofosbuvir both in vitro and in vivo

2019 ◽  
Vol 13 (1) ◽  
pp. e0007072 ◽  
Author(s):  
Caroline S. de Freitas ◽  
Luiza M. Higa ◽  
Carolina Q. Sacramento ◽  
André C. Ferreira ◽  
Patrícia A. Reis ◽  
...  
Keyword(s):  
Yellow Fever ◽  
Yellow Fever Virus ◽  
Fever Virus

scholarly journals AT-752, a double prodrug of a guanosine nucleotide analog, inhibits yellow fever virus in a hamster model

2021 ◽  
Author(s):  
Kai Lin ◽  
Steven S Good ◽  
Justin G. Julander ◽  
Abbie Weight ◽  
Adel Moussa
Keyword(s):  
Yellow Fever ◽  
Yellow Fever Virus ◽  
Limit Of Detection ◽  
Virus Titer ◽  
Fever Virus ◽  
Effective Vaccine ◽  
Hamster Model ◽  
Nucleotide Analog

Yellow fever virus (YFV) is a zoonotic pathogen re-emerging in parts of the world, causing a viral hemorrhagic fever associated with high mortality rates. While an effective vaccine is available, having an effective antiviral against YFV is critical against unexpected outbreaks, or when vaccination is not recommended. We have previously identified AT-281, the free base of AT-752, an orally available double prodrug of a guanosine nucleotide analog, as a potent inhibitor of YFV in vitro , with a 50% effective concentration (EC 50 ) of 0.31 µM. In hamsters infected with YFV (Jimenez strain), viremia rose about 4 log 10 -fold and serum alanine aminotransferase (ALT) 2-fold compared to sham-infected animals. Treatment with 1000 mg/kg AT-752 for 7 days, initiated 4 h prior to viral challenge, reduced viremia to below the limit of detection by day 4 post infection (pi) and returned ALT to normal levels by day 6 pi. When treatment with AT-752 was initiated 2 days pi, the virus titer and ALT dropped >2 log 10 and 53% by day 4 and 6 pi, respectively. In addition, at 21 days pi, 70 – 100% of the infected animals in the treatment groups survived compared to 0% of the untreated group (p<0.001). Moreover, in vivo formation of the active triphosphate metabolite AT-9010 was measured in the animal tissues, with the highest concentrations in liver and kidney, organs that are vulnerable to the virus. The demonstrated in vivo activity of AT-752 suggests that it is a promising compound for clinical development in the treatment of YFV infection.

scholarly journals E Protein Domain III Determinants of Yellow Fever Virus 17D Vaccine Strain Enhance Binding to Glycosaminoglycans, Impede Virus Spread, and Attenuate Virulence

2008 ◽  
Vol 82 (12) ◽  
pp. 6024-6033 ◽  
Author(s):  
Eva Lee ◽  
Mario Lobigs
Keyword(s):  
Yellow Fever ◽  
Yellow Fever Virus ◽  
Fever Virus ◽  
Protein Domain ◽  
Type I ◽  
Wild Type ◽  
E Protein ◽  
Virulence Attenuation ◽  
Domain Iii

ABSTRACT The yellow fever virus (YFV) 17D strain is one of the most effective live vaccines for human use, but the in vivo mechanisms for virulence attenuation of the vaccine and the corresponding molecular determinants remain elusive. The vaccine differs phenotypically from wild-type YFV by the loss of viscerotropism, despite replicative fitness in cell culture, and genetically by 20 amino acid changes predominantly located in the envelope (E) protein. We show that three residues in E protein domain III inhibit spread of 17D in extraneural tissues and attenuate virulence in type I/II interferon-deficient mice. One of these residues (Arg380) is a dominant glycosaminoglycan-binding determinant, which mainly accounts for more rapid in vivo clearance of 17D from the bloodstream in comparison to 17D-derived variants with wild-type-like E protein. While other mutations will account for loss of neurotropism and phenotypic stability, the described impact of E protein domain III changes on virus dissemination and virulence is the first rational explanation for the safety of the 17D vaccine in humans.

RNA interference inhibits yellow fever virus replication in vitro and in vivo

Virus Genes ◽  
2009 ◽  
Vol 38 (2) ◽  
pp. 224-231 ◽  
Author(s):  
Carolina C. Pacca ◽  
Adriana A. Severino ◽  
Adriano Mondini ◽  
Paula Rahal ◽  
Solange G. P. D’avila ◽  
...  
Keyword(s):  
Rna Interference ◽  
Yellow Fever ◽  
Virus Replication ◽  
Yellow Fever Virus ◽  
Fever Virus

In vitro and in vivo antiviral properties of sulfated galactomannans against yellow fever virus (BeH111 strain) and dengue 1 virus (Hawaii strain)

2003 ◽  
Vol 60 (3) ◽  
pp. 201-208 ◽  
Author(s):  
Lucy Ono ◽  
Wagner Wollinger ◽  
Iray M Rocco ◽  
Terezinha L.M Coimbra ◽  
Philip A.J Gorin ◽  
...  
Keyword(s):  
Yellow Fever ◽  
Yellow Fever Virus ◽  
Fever Virus

scholarly journals Molecular determinants of Yellow Fever Virus pathogenicity in Syrian Golden Hamsters: one mutation away from virulence

2018 ◽  
Author(s):  
Raphaëlle Klitting ◽  
Laura Roth ◽  
Félix A. Rey ◽  
Xavier de Lamballerie
Keyword(s):  
Yellow Fever ◽  
Reverse Genetics ◽  
Yellow Fever Virus ◽  
Virulent Strain ◽  
Fever Virus ◽  
Viral Loads ◽  
Synonymous Mutations ◽  
E Protein ◽  
Α Helix

ABSTRACTYellow fever virus (Flavivirusgenus) is an arthropod-borne pathogen which can infect humans, causing a severe viscerotropic disease with a high mortality rate. Adapted viral strains allow the reproduction of yellow fever disease in hamsters with features similar to the human disease. Here, we used the Infectious Subgenomic Amplicons reverse genetics method to produce an equivalent to the hamster-virulent strain, Yellow FeverAp7, by introducing a set of 4 synonymous and 6 non-synonymous mutations into a single subgenomic amplicon, derived from the sequence of theAsibistrain. The resulting strain, Yellow FeverAp7M, induced a disease similar to that described forAp7in terms of symptoms, weight evolution, viral loads in the liver and lethality. Using the same methodology, we produced mutant strains derived from eitherAp7MorAsibiviruses and investigated the role of each ofAp7Mnon-synonymous mutations in itsin vivophenotype. This allowed identifying key components of the virulence mechanism in hamsters. InAp7Mvirus, the reversion of either E/Q27H or E/D155A mutations, led to an important reduction of both virulence andin vivoreplicative fitness. In addition, the introduction of the single D155AAp7Mmutation within the E protein of theAsibivirus was sufficient to drastically modify its phenotype in hamsters towards both a greater replication efficiency and virulence. Finally, inspection of theAsibistrain E protein structure combined toin vivotesting revealed the importance of an exposed α-helix in domain I, containing residues 154 and 155, forAp7Mvirulence in hamsters.

scholarly journals Yellow fever virus is susceptible to sofosbuvir both in vitro and in vivo

2018 ◽  
Author(s):  
Caroline S. de Freitas ◽  
Luiza M. Higa ◽  
Carolina Sacramento ◽  
André C. Ferreira ◽  
Patrícia A. Reis ◽  
...  
Keyword(s):  
Yellow Fever ◽  
Yellow Fever Virus ◽  
Clinical Results ◽  
Fever Virus ◽  
Health Concern ◽  
Public Health Concern ◽  
Human Hepatoma Cells ◽  
Attractive Option

AbstractYellow fever virus (YFV) is a member of the Flaviviridae family, that causes major mortality. In Brazil, YFV activity increased in the last years. It has been registered that sylvatic, instead of urban, yellow fever (YF) leads our contemporary public health concern. Low vaccinal coverage leaves the human population near the jangle vulnerable to the outbreak, making it necessary to identify therapeutic options. Repurposing of clinically approved antiviral drugs represents an alternative for such identification. Other Flaviviruses, such Zika (ZIKV) and dengue (DENV) viruses, are susceptible to Sofosbuvir, a clinically approved drug against hepatitis C virus (HCV). Moreover, sofosbuvir has a safety record on critically ill hepatic patients, making it an attractive option. Our data show that YFV RNA polymerase uses conserved amino acid resides for nucleotide binding to dock sofosbuvir. This drug inhibited YFV replication in different lineages of human hepatoma cells, Huh-7 and HepG2, with EC50 value of 4.8 µM. Sofosbuvir protected YFV-infected neonatal Swiss mice from mortality and weight loss. Our pre-clinical results indicate that sofosbuvir could represent an option against YFV.

scholarly journals Exploratory re-encoding of Yellow Fever Virus genome: new insights for the design of live-attenuated viruses

2018 ◽  
Author(s):  
R. Klitting ◽  
T. Riziki ◽  
G. Moureau ◽  
G. Piorkowski ◽  
E. A. Gould ◽  
...  
Keyword(s):  
Yellow Fever ◽  
Yellow Fever Virus ◽  
Fever Virus ◽  
Coding Region ◽  
Live Attenuated Vaccine ◽  
Replicative Fitness ◽  
Synonymous Mutations ◽  
Attenuated Viruses

AbstractVirus attenuation by genome re-encoding is a pioneering approach for generating effective live-attenuated vaccine candidates. Its core principle is to introduce a large number of synonymous substitutions into the viral genome to produce stable attenuation of the targeted virus. Introduction of large numbers of mutations has also been shown to maintain stability of the attenuated phenotype by lowering the risk of reversion and recombination of re-encoded genomes. Identifying mutations with low fitness cost is pivotal as this increases the number that can be introduced and generates more stable and attenuated viruses. Here, we sought to identify mutations with low deleterious impact on thein vivoreplication and virulence of yellow fever virus (YFV). Following comparative bioinformatic analyses of flaviviral genomes, we categorized synonymous transition mutations according to their impact on CpG/UpA composition and secondary RNA structures. We then designed 17 re-encoded viruses with 100-400 synonymous mutations in the NS2A-to-NS4B coding region of YFVAsibiandAp7M(hamster-adapted) genomes. Each virus contained a panel of synonymous mutations designed according to the above categorisation criteria. The replication and fitness characteristics of parent and re-encoded viruses were comparedin vitrousing cell culture competition experiments.In vivolaboratory hamster models were also used to compare relative virulence and immunogenicity characteristics. Most of the re-encoded strains showed no decrease in replicative fitnessin vitro. However, they showed reduced virulence and, in some instances, decreased replicative fitnessin vivo. Importantly, the most attenuated of the re-encoded strains induced robust, protective immunity in hamsters following challenge withAp7M, a virulent virus. Overall, the introduction of transitions with no or a marginal increase in the number of CpG/UpA dinucleotides had the mildest impact on YFV replication and virulencein vivo. Thus, this strategy can be incorporated in procedures for the finely tuned creation of substantially re-encoded viral genomes.

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