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 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.

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 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 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.

scholarly journals Yellow Fever Virus Down-Regulates mRNA Expression of SOCS1 in the Initial Phase of Infection in Human Cell Lines

Viruses ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 802
Author(s):  
Michael B. Yakass ◽  
David Franco ◽  
Osbourne Quaye
Keyword(s):  
Mrna Expression ◽  
Yellow Fever ◽  
Yellow Fever Virus ◽  
Expression Patterns ◽  
Fever Virus ◽  
Effective Vaccine ◽  
Interferon Β ◽  
Infected Cells ◽  
Insight Into

Flaviviruses are constantly evolving diverse immune evasion strategies, and the exploitation of the functions of suppressors of cytokine signalling (SOCS) and protein inhibitors of activated STATs (PIAS) to favour virus replication has been described for Dengue and Japanese encephalitis viruses but not for yellow fever virus (YFV), which is still of global importance despite the existence of an effective vaccine. Some mechanisms that YFV employs to evade host immune defence has been reported, but the expression patterns of SOCS and PIAS in infected cells is yet to be determined. Here, we show that SOCS1 is down-regulated early in YFV-infected HeLa and HEK 293T cells, while SOCS3 and SOCS5 are not significantly altered, and PIAS mRNA expression appears to follow a rise-dip pattern akin to circadian-controlled genes. We also demonstrate that YFV evades interferon-β application to produce comparable viral titres. This report provides initial insight into the in vitro expression dynamics of SOCS and PIAS upon YFV infection and a basis for further investigation into SOCS/PIAS expression and how these modulate the immune response in animal models.

scholarly journals Natural Compounds against Flaviviral Infections

2013 ◽  
Vol 8 (10) ◽  
pp. 1934578X1300801 ◽  
Author(s):  
Md Abubakr ◽  
Subhash C Mandal ◽  
Sugato Banerjee
Keyword(s):  
Public Health ◽  
West Nile Virus ◽  
Yellow Fever ◽  
Chikungunya Virus ◽  
Yellow Fever Virus ◽  
Health Concern ◽  
Public Health Concern ◽  
Natural Sources ◽  
The Tropics ◽  
Large Sections

Arthropod borne flaviviral diseases are a major public health concern in the tropics. However, the majority of cases are associated with Dengue virus (DENV), Yellow Fever virus (YFV), West Nile virus (WNV) and Chikungunya virus (CHIKV) infections. Despite their profound clinical and economic impact among large sections of the population there is a lack of effective treatment against these diseases. A large number of plants are available in nature, which may act as a source for lead molecules against various diseases including arthropod borne flaviviral infections. In this review we discuss various crude extracts as well as purified compounds from natural sources with promising anti-DENV, YFV, WNV and CHIKV activity.

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