scholarly journals Yellow Fever Virus NS2B–NS3 Protease: Charged-to-Alanine Mutagenesis and Deletion Analysis Define Regions Important for Protease Complex Formation and Function

Virology ◽  
2000 ◽  
Vol 275 (2) ◽  
pp. 335-347 ◽  
Author(s):  
Deborah A. Droll ◽  
H.M. Krishna Murthy ◽  
Thomas J. Chambers
Keyword(s):  
Complex Formation ◽  
Yellow Fever ◽  
Yellow Fever Virus ◽  
Fever Virus ◽  
Deletion Analysis ◽  
And Function ◽  
Ns3 Protease

scholarly journals Yellow fever virus NS3 protease: peptide-inhibition studies

2007 ◽  
Vol 88 (8) ◽  
pp. 2223-2227 ◽  
Author(s):  
Kristina Löhr ◽  
John E. Knox ◽  
Wai Yee Phong ◽  
Ngai Ling Ma ◽  
Zheng Yin ◽  
...  
Keyword(s):  
Yellow Fever ◽  
Yellow Fever Virus ◽  
Homology Model ◽  
Enzymic Activity ◽  
Fever Virus ◽  
Catalytically Active ◽  
Relationship Of ◽  
Ns3 Protease ◽  
Inhibition Studies ◽  
Factor Sequence

A recombinant form of yellow fever virus (YFV) NS3 protease, linked via a nonapeptide to the minimal NS2B co-factor sequence (CF40-gly-NS3pro190), was expressed in Escherichia coli and shown to be catalytically active. It efficiently cleaved the fluorogenic tetrapeptide substrate Bz-norleucine-lysine-arginine-arginine-AMC, which was previously optimized for dengue virus NS2B/3 protease. A series of small peptidic inhibitors based on this substrate sequence readily inhibited its enzymic activity. To understand the structure–activity relationship of the inhibitors, they were docked into a homology model of the YFV NS2B/NS3 protease structure. The results revealed that the P1 and P2 positions are most important for inhibitor binding, whilst the P3 and P4 positions have much less effect. These findings indicate that the characteristics of YFV protease are very similar to those reported for dengue and West Nile virus proteases, and suggest that pan-flavivirus NS3 protease drugs may be developed for flaviviral diseases.

Structural characterization and polymorphism analysis of the NS2B-NS3 protease from the 2017 Brazilian circulating strain of Yellow Fever virus

2020 ◽  
Vol 1864 (4) ◽  
pp. 129521 ◽  
Author(s):  
Gabriela Dias Noske ◽  
Victor Oliveira Gawriljuk ◽  
Rafaela Sachetto Fernandes ◽  
Nathalia Dias Furtado ◽  
Myrna Cristina Bonaldo ◽  
...  
Keyword(s):  
Yellow Fever ◽  
Structural Characterization ◽  
Yellow Fever Virus ◽  
Fever Virus ◽  
Polymorphism Analysis ◽  
Ns3 Protease

scholarly journals Virtual Screening of FDA Approved Drugs Library to Identify a Potential Inhibitor against NS2B-NS3 Protease of Yellow Fever Virus

2021 ◽  
pp. 177-186
Author(s):  
Hasanain Abdulhameed Odhar ◽  
Salam Waheed Ahjel ◽  
Ali A. Mohammed Ali Albeer ◽  
Ahmed Fadhil Hashim ◽  
Suhad Sami Humadi
Keyword(s):  
Virtual Screening ◽  
Yellow Fever ◽  
Active Site ◽  
Yellow Fever Virus ◽  
Fever Virus ◽  
Dynamics Simulation ◽  
Hemorrhagic Disease ◽  
Approved Drugs ◽  
Ns3 Protease ◽  
Fda Approved Drugs

Yellow fever is a neglected hemorrhagic disease with a high case fatality rate ranging between 25% and 50% for the hospitalized patients. Yellow fever disease is caused by a zoonotic pathogen known as yellow fever virus. This RNA virus is usually transmitted by mosquitos and it is considered endemic in the tropical regions of South America and Africa. Although an effective vaccine is available for yellow fever virus, no antiviral drug is yet licensed against the disease. Thus, yellow fever virus is still representing a re-emerging threat among unvaccinated individuals in endemic regions. The NS2B-NS3 protease seems to play an important role in yellow fever virus replication cycle. As such, the NS2B-NS3 protease may represent a potential target for structure-based drug design and discovery. In this direction, computational approaches like virtual screening can be utilized to hasten the design of novel antivirals and/ or repurposing an already FDA approved drugs. In this in silico study, an FDA approved drugs library was screened against NS2B-NS3 protease crystal of yellow fever virus. Then the best hits with least energy of binding and ability of hydrogen bonding with key residues of protease active site were then selected and submitted to molecular dynamics simulation. And throughout simulation interval, only Olsalazine was able to stay in close proximity to the active site of protease crystal with least average MM-PBSA binding energy as compared to Dantrolene, Belinostat and Linezolid. This indicates that Olsalazine may have the best capacity to bind to NS2B-NS3 protease and interfere with its activity.

scholarly journals Yellow fever virus NS2B/NS3 protease: Hydrolytic Properties and Substrate Specificity

2011 ◽  
Vol 407 (4) ◽  
pp. 640-644 ◽  
Author(s):  
Marcia Y. Kondo ◽  
Lilian C.G. Oliveira ◽  
Debora N. Okamoto ◽  
Marina R.T. de Araujo ◽  
Claudia N. Duarte dos Santos ◽  
...  
Keyword(s):  
Substrate Specificity ◽  
Yellow Fever ◽  
Yellow Fever Virus ◽  
Fever Virus ◽  
Ns3 Protease

scholarly journals Genomic and structural features of the Yellow Fever virus from the 2016-2017 Brazilian outbreak

2017 ◽  
Author(s):  
Mariela Martínez Gómez ◽  
Filipe Vieira Santos de Abreu ◽  
Alexandre Araujo Cunha dos Santos ◽  
Iasmim Silva de Mello ◽  
Marta Pereira Santos ◽  
...  
Keyword(s):  
Amino Acid ◽  
Yellow Fever ◽  
Yellow Fever Virus ◽  
Viral Proteins ◽  
Structural Features ◽  
Fever Virus ◽  
Viral Fitness ◽  
And Function ◽  
Enzyme Structure And Function ◽  
Unique Amino Acid

ABSTRACTBrazil has been suffering a severe sylvatic epidemic of yellow fever virus (YFV) since late 2016. Analysis of full-length YFV genomes from all hosts involved in the Brazilian 2017 outbreak reveals that they belong to sub-lineage 1E within modern-lineage, but display several unique amino acid substitutions in highly conserved positions at NS3 and NS5 viral proteins. Evolutionary analyses indicate that YFV carrying that set of amino acid substitution circulates in the Southern Brazilian region for several months before being detected in December 2016. Structural and selection analyses support that some of these substitutions were under positive selection and could impact enzyme structure and function. Altogether, this evidence demonstrated that the current Brazilian YFV carries unique amino acid signatures in the non-structural proteins and support the hypothesis that those substitutions may be affecting the viral fitness and transmissibility.

scholarly journals Yellow fever virus NS2B–NS3 protease: characterization of charged-to-alanine mutant and revertant viruses and analysis of polyprotein-cleavage activities

2005 ◽  
Vol 86 (5) ◽  
pp. 1403-1413 ◽  
Author(s):  
Thomas J. Chambers ◽  
Deborah A. Droll ◽  
Yujia Tang ◽  
Yan Liang ◽  
Vannakambadi K. Ganesh ◽  
...  
Keyword(s):  
Cell Culture ◽  
Yellow Fever ◽  
Yellow Fever Virus ◽  
Fever Virus ◽  
Plaque Size ◽  
Protease Domain ◽  
Small Plaque ◽  
Cleavage Activity ◽  
Cellular Expression ◽  
Ns3 Protease

A series of 46 charged-to-alanine mutations in the yellow fever virus NS2B–NS3 protease, previously characterized in cell-free and transient cellular expression systems, was tested for their effects on virus recovery. Four distinct plaque phenotypes were observed in cell culture: parental plaque-size (13 mutants), reduced plaque-size (17 mutants), small plaque-size (8 mutants) and no plaque-formation (8 mutants). No mutants displayed any temperature sensitivity based on recovery of virus after RNA transfection at 32 versus 37 °C. Most small plaque-mutants were defective in growth efficiency compared with parental virus. However not all small plaque-mutants had defective 2B/3 cleavage, with some showing selective defects at other non-structural protein cleavage sites. Revertant viruses were recovered for six mutations that caused reduced plaque sizes. Same-site and second-site mutations occurred in NS2B, and one second-site mutation occurred in the NS3 protease domain. Some reversion mutations ameliorated defects in cleavage activity and plaque size caused by the original mutation. These data indicate that certain mutations that reduce NS2B–NS3 protease cleavage activity cause growth restriction of yellow fever virus in cell culture. However, for at least two mutations, processing defects other than impaired cleavage activity at the 2B/3 site may account for the mutant phenotype. The existence of reversion mutations primarily in NS2B rather than NS3, suggests that the protease domain is less tolerant of structural perturbation compared with the NS2B protein.

scholarly journals Yellow fever virus outbreak in Brazil under current and future climate

2021 ◽  
Vol 6 ◽  
pp. 664-677
Author(s):  
Tara Sadeghieh ◽  
Jan M. Sargeant ◽  
Amy L. Greer ◽  
Olaf Berke ◽  
Guillaume Dueymes ◽  
...  
Keyword(s):  
Yellow Fever ◽  
Yellow Fever Virus ◽  
Fever Virus ◽  
Future Climate

scholarly journals Yellow Fever Outbreak in Eastern Senegal, 2020–2021

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1475
Author(s):  
Moussa Moïse Diagne ◽  
Marie Henriette Dior Ndione ◽  
Alioune Gaye ◽  
Mamadou Aliou Barry ◽  
Diawo Diallo ◽  
...  
Keyword(s):  
Yellow Fever ◽  
Yellow Fever Virus ◽  
Mosquito Species ◽  
Virus Transmission ◽  
Genomic Analysis ◽  
Hemorrhagic Fever ◽  
Fever Virus ◽  
World Health ◽  
Effective Vaccine ◽  
Ministry Of Health

Yellow fever virus remains a major threat in low resource countries in South America and Africa despite the existence of an effective vaccine. In Senegal and particularly in the eastern part of the country, periodic sylvatic circulation has been demonstrated with varying degrees of impact on populations in perpetual renewal. We report an outbreak that occurred from October 2020 to February 2021 in eastern Senegal, notified and managed through the synergistic effort yellow fever national surveillance implemented by the Senegalese Ministry of Health in collaboration with the World Health Organization, the countrywide 4S network set up by the Ministry of Health, the Institut Pasteur de Dakar, and the surveillance of arboviruses and hemorrhagic fever viruses in human and vector populations implemented since mid 2020 in eastern Senegal. Virological analyses highlighted the implication of sylvatic mosquito species in virus transmission. Genomic analysis showed a close relationship between the circulating strain in eastern Senegal, 2020, and another one from the West African lineage previously detected and sequenced two years ago from an unvaccinated Dutch traveler who visited the Gambia and Senegal before developing signs after returning to Europe. Moreover, genome analysis identified a 6-nucleotide deletion in the variable domain of the 3′UTR with potential impact on the biology of the viral strain that merits further investigations. Integrated surveillance of yellow fever virus but also of other arboviruses of public health interest is crucial in an ecosystem such as eastern Senegal.

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