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Article ; Online: Phenotypic and Genetic Studies of the Viral Lineage Associated with the Recent Yellow Fever Outbreak in Brazil.

Furtado, Nathália Dias / Gómez, Mariela Martínez / de Mello, Iasmim Silva / Fernandes, Déberli Ruiz / Bonaldo, Myrna Cristina

Viruses

2022 Volume 14, Issue 8

Abstract: Yellow fever virus (YFV) caused an outbreak in the Brazilian Southeast from 2016 to 2019, of the most significant magnitude since the 1900s. An investigation of the circulating virus revealed that most of the genomes detected in this period carried nine ... ...

Abstract	Yellow fever virus (YFV) caused an outbreak in the Brazilian Southeast from 2016 to 2019, of the most significant magnitude since the 1900s. An investigation of the circulating virus revealed that most of the genomes detected in this period carried nine unique amino acid polymorphisms, with eight located in the non-structural proteins NS3 and NS5, which are pivotal for viral replication. To elucidate the effect of these amino acid changes on viral infection, we constructed viruses carrying amino acid alterations in NS3 and NS5, performed infection in different cells, and assessed their neurovirulence in BALB/c mice and infected AG129 mice. We observed that the residues that compose the YFV 2016-2019 molecular signature in the NS5 protein might have been related to an attenuated phenotype, and that the alterations in the NS3 protein only slightly affected viral infection in AG129 mice, increasing to a low extent the mortality rate of these animals. These results contributed to unveiling the role of specific naturally occurring amino acid changes in the circulating strain of YFV in Brazil.
MeSH term(s)	Amino Acids/genetics ; Animals ; Brazil/epidemiology ; Disease Outbreaks ; Mice ; Phenotype ; Yellow Fever/epidemiology ; Yellow fever virus/genetics
Chemical Substances	Amino Acids
Language	English
Publishing date	2022-08-19
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v14081818
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Phenotypic and Genetic Studies of the Viral Lineage Associated with the Recent Yellow Fever Outbreak in Brazil

Furtado, Nathália Dias / Gómez, Mariela Martínez / de Mello, Iasmim Silva / Fernandes, Déberli Ruiz / Bonaldo, Myrna Cristina

Viruses. 2022 Aug. 19, v. 14, no. 8

2022

Abstract	Yellow fever virus (YFV) caused an outbreak in the Brazilian Southeast from 2016 to 2019, of the most significant magnitude since the 1900s. An investigation of the circulating virus revealed that most of the genomes detected in this period carried nine unique amino acid polymorphisms, with eight located in the non-structural proteins NS3 and NS5, which are pivotal for viral replication. To elucidate the effect of these amino acid changes on viral infection, we constructed viruses carrying amino acid alterations in NS3 and NS5, performed infection in different cells, and assessed their neurovirulence in BALB/c mice and infected AG129 mice. We observed that the residues that compose the YFV 2016–2019 molecular signature in the NS5 protein might have been related to an attenuated phenotype, and that the alterations in the NS3 protein only slightly affected viral infection in AG129 mice, increasing to a low extent the mortality rate of these animals. These results contributed to unveiling the role of specific naturally occurring amino acid changes in the circulating strain of YFV in Brazil.
Keywords	Yellow fever virus ; amino acids ; genome ; mortality ; phenotype ; virus replication ; viruses ; yellow fever ; Brazil
Language	English
Dates of publication	2022-0819
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v14081818
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Article ; Online: Amino Acid Polymorphisms on the Brazilian Strain of Yellow Fever Virus Methyltransferase Are Related to the Host's Immune Evasion Mediated by Type I Interferon.

Furtado, Nathália Dias / de Mello, Iasmim Silva / de Godoy, Andre Schutzer / Noske, Gabriela Dias / Oliva, Glaucius / Canard, Bruno / Decroly, Etienne / Bonaldo, Myrna C

Viruses

2023 Volume 15, Issue 1

Abstract: Since late 2016, a yellow fever virus (YFV) variant carrying a set of nine amino acid variations has circulated in South America. Three of them were mapped on the methyltransferase (MTase) domain of viral NS5 protein. To assess whether these changes ... ...

Abstract	Since late 2016, a yellow fever virus (YFV) variant carrying a set of nine amino acid variations has circulated in South America. Three of them were mapped on the methyltransferase (MTase) domain of viral NS5 protein. To assess whether these changes affected viral infectivity, we synthesized YFV carrying the MTase of circulating lineage as well as its isoform with the residues of the previous strains (NS5 K101R, NS5 V138I, and NS5 G173S). We observed a slight difference in viral growth properties and plaque phenotype between the two synthetic YFVs. However, the MTase polymorphisms associated with the Brazilian strain of YFV (2016-2019) confer more susceptibility to the IFN-I. In addition, in vitro MTase assay revealed that the interaction between the YFV MTase and the methyl donor molecule (SAM) is altered in the Brazilian MTase variant. Altogether, the results reported here describe that the MTase carrying the molecular signature of the Brazilian YFV circulating since 2016 might display a slight decrease in its catalytic activity but virtually no effect on viral fitness in the parameters comprised in this study. The most marked influence of these residues stands in the immune escape against the antiviral response mediated by IFN-I.
MeSH term(s)	Yellow fever virus/physiology ; Interferon Type I/genetics ; Amino Acids ; Immune Evasion ; Brazil ; Methyltransferases/metabolism ; Viral Nonstructural Proteins/genetics
Chemical Substances	Interferon Type I ; Amino Acids ; Methyltransferases (EC 2.1.1.-) ; Viral Nonstructural Proteins
Language	English
Publishing date	2023-01-10
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v15010191
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Article ; Online: Reduced ability to neutralize the Omicron variant among adults after infection and complete vaccination with BNT162b2, ChAdOx1, or CoronaVac and heterologous boosting.

Espíndola, Otávio Melo / Fuller, Trevon L / de Araújo, Mia Ferreira / Tort, Luis Fernando Lopez / Guaraldo, Lusiele / Calvet, Guilherme / Resende, Paola / Bonaldo, Myrna / Whitworth, Jimmy / Smith, Chris / Siqueira, Marilda / Brasil, Patrícia

Scientific reports

2023 Volume 13, Issue 1, Page(s) 7437

Abstract: COVID-19 vaccines have dramatically reduced rates of severe infection requiring hospitalization. However, SARS-CoV-2 variants have reduced vaccine effectiveness at preventing any symptomatic infection. This real-world study analyzed binding and ... ...

Abstract	COVID-19 vaccines have dramatically reduced rates of severe infection requiring hospitalization. However, SARS-CoV-2 variants have reduced vaccine effectiveness at preventing any symptomatic infection. This real-world study analyzed binding and neutralizing antibodies generated after complete vaccination and boosting across three vaccine platforms. Binding antibodies decayed most slowly in people under 60 with hybrid immunity. Neutralizing antibodies against Omicron BA.1 were reduced compared to other variants. The anamnestic anti-spike IgG response to the first boost was more pronounced than after the second boost. Monitoring of the effects of SARS-CoV-2 mutations on disease severity and the effectiveness of therapeutics is warranted.
MeSH term(s)	Adult ; Humans ; COVID-19 Vaccines ; BNT162 Vaccine ; COVID-19/prevention & control ; SARS-CoV-2/genetics ; Vaccination ; Antibodies, Neutralizing ; Antibodies, Viral
Chemical Substances	sinovac COVID-19 vaccine ; COVID-19 Vaccines ; BNT162 Vaccine ; Antibodies, Neutralizing ; Antibodies, Viral
Language	English
Publishing date	2023-05-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-34035-9
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Article ; Online: Infectious SARS-CoV-2 Particles from Rectal Swab Samples from COVID-19 Patients in Brazil.

Ribeiro, Ieda Pereira / Nascimento, Lilian Gonçalves do / Tort, Luis Fernando Lopez / Pereira, Elisa Cavalcante / Menezes, Lidiane Souza Raphael / Malta, Fabio Correia / Oliveira, Barbara Cristina Euzebio Pereira Dias de / Rodrigues, João Paulo / Manso, Pedro Paulo de Abreu / Pelajo, Marcelo / Bonaldo, Myrna Cristina / Silva, Paola Cristina Resende / Siqueira, Marilda Mendonça / Brasil, Patricia / Fumian, Tulio Machado

Viruses

2023 Volume 15, Issue 5

Abstract: The main objective of this study was to investigate the dynamic of SARS-CoV-2 viral excretion in rectal swab (RS), saliva, and nasopharyngeal swab (NS) samples from symptomatic patients and asymptomatic contacts. In addition, in order to evaluate the ... ...

Abstract	The main objective of this study was to investigate the dynamic of SARS-CoV-2 viral excretion in rectal swab (RS), saliva, and nasopharyngeal swab (NS) samples from symptomatic patients and asymptomatic contacts. In addition, in order to evaluate the replication potential of SARS-CoV-2 in the gastrointestinal (GI) tract and the excretion of infectious SARS-CoV-2 from feces, we investigated the presence of subgenomic nucleoprotein gene (N) mRNA (sgN) in RS samples and cytopathic effects in Vero cell culture. A prospective cohort study was performed to collect samples from symptomatic patients and contacts in Rio de Janeiro, Brazil, from May to October 2020. One hundred and seventy-six patients had samples collected at home visits and/or during the follow up, resulting in a total of 1633 RS, saliva, or NS samples. SARS-CoV-2 RNA was detected in 130 (73.9%) patients who had at least one sample that tested positive for SARS-CoV-2. The presence of replicating SARS-CoV-2 in RS samples, measured by the detection of sgN mRNA, was successfully achieved in 19.4% (6/31) of samples, whilst infectious SARS-CoV-2, measured by the generation of cytopathic effects in cell culture, was identified in only one RS sample. Although rare, our results demonstrated the replication capacity of SARS-CoV-2 in the GI tract, and infectious viruses in one RS sample. There is still a gap in the knowledge regarding SARS-CoV-2 fecal-oral transmission. Additional studies are warranted to investigate fecal or wastewater exposure as a risk factor for transmission in human populations.
MeSH term(s)	Humans ; COVID-19/diagnosis ; COVID-19/epidemiology ; SARS-CoV-2/genetics ; RNA, Viral/genetics ; Brazil/epidemiology ; Prospective Studies ; Communicable Diseases
Chemical Substances	RNA, Viral
Language	English
Publishing date	2023-05-11
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v15051152
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Article ; Online: Ecological, Genetic, and Phylogenetic Aspects of YFV 2017-2019 Spread in Rio de Janeiro State.

Ribeiro, Ieda Pereira / Delatorre, Edson / de Abreu, Filipe Vieira Santos / Dos Santos, Alexandre Araújo Cunha / Furtado, Nathália Dias / Ferreira-de-Brito, Anielly / de Pina-Costa, Anielle / Neves, Maycon Sebastião Alberto Santos / de Castro, Márcia Gonçalves / Motta, Monique de Albuquerque / Brasil, Patricia / Lourenço-de-Oliveira, Ricardo / Bonaldo, Myrna Cristina

Viruses

2023 Volume 15, Issue 2

Abstract: In Brazil, a yellow fever (YF) outbreak was reported in areas considered YF-free for decades. The low vaccination coverage and the increasing forest fragmentation, with the wide distribution of vector mosquitoes, have been related to yellow fever virus ( ... ...

Abstract	In Brazil, a yellow fever (YF) outbreak was reported in areas considered YF-free for decades. The low vaccination coverage and the increasing forest fragmentation, with the wide distribution of vector mosquitoes, have been related to yellow fever virus (YFV) transmission beyond endemic areas since 2016. Aiming to elucidate the molecular and phylogenetic aspects of YFV spread on a local scale, we generated 43 new YFV genomes sampled from humans, non-human primates (NHP), and primarily, mosquitoes from highly heterogenic areas in 15 localities from Rio de Janeiro (RJ) state during the YFV 2016-2019 outbreak in southeast Brazil. Our analysis revealed that the genetic diversity and spatial distribution of the sylvatic transmission of YFV in RJ originated from at least two introductions and followed two chains of dissemination, here named the YFV RJ-I and YFV RJ-II clades. They moved with similar dispersal speeds from the north to the south of the RJ state in parallel directions, separated by the Serra do Mar Mountain chain, with YFV RJ-I invading the north coast of São Paulo state. The YFV RJ-I clade showed a more significant heterogeneity across the entire polyprotein. The YFV RJ-II clade, with only two amino acid polymorphisms, mapped at NS1 (I1086V), present only in mosquitoes at the same locality and NS4A (I2176V), shared by all YFV clade RJ-II, suggests a recent clustering of YFV isolates collected from different hosts. Our analyses strengthen the role of surveillance, genomic analyses of YVF isolated from other hosts, and environmental studies into the strategies to forecast, control, and prevent yellow fever outbreaks.
MeSH term(s)	Animals ; Yellow fever virus/genetics ; Yellow Fever/epidemiology ; Brazil/epidemiology ; Phylogeny ; Mosquito Vectors ; Culicidae ; Forests
Language	English
Publishing date	2023-02-04
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v15020437
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Article ; Online: A Zika virus primary isolate induces neuroinflammation, compromises the blood-brain barrier and upregulates CXCL12 in adult macaques.

Panganiban, Antonito T / Blair, Robert V / Hattler, Julian B / Bohannon, Diana G / Bonaldo, Myrna C / Schouest, Blake / Maness, Nicholas J / Kim, Woong-Ki

Brain pathology (Zurich, Switzerland)

2020 Volume 30, Issue 6, Page(s) 1017–1027

Abstract: Zika virus (ZIKV) is a flavivirus that can cause neuropathogenesis in adults and fetal neurologic malformation following the infection of pregnant women. We used a nonhuman primate model, the Indian-origin Rhesus macaque (IRM), to gain insight into virus- ...

Abstract	Zika virus (ZIKV) is a flavivirus that can cause neuropathogenesis in adults and fetal neurologic malformation following the infection of pregnant women. We used a nonhuman primate model, the Indian-origin Rhesus macaque (IRM), to gain insight into virus-associated hallmarks of ZIKV-induced adult neuropathology. We find that the virus causes prevalent acute and chronic neuroinflammation and chronic disruption of the blood-brain barrier (BBB) in adult animals. ZIKV infection resulted in specific short- and long-term augmented expression of the chemokine CXCL12 in the central nervous system (CNS)of adult IRMs. Moreover, CXCL12 expression persists long after the initial viral infection is apparently cleared. CXCL12 plays a key role both in regulating lymphocyte trafficking through the BBB to the CNS and in mediating repair of damaged neural tissue including remyelination. Understanding how CXCL12 expression is controlled will likely be of central importance in the definition of ZIKV-associated neuropathology in adults.
MeSH term(s)	Animals ; Blood-Brain Barrier/metabolism ; Blood-Brain Barrier/pathology ; Blood-Brain Barrier/virology ; Brain/metabolism ; Brain/pathology ; Brain/virology ; Chemokine CXCL12/metabolism ; Disease Models, Animal ; Encephalitis/metabolism ; Encephalitis/pathology ; Encephalitis/virology ; Female ; Macaca mulatta ; Male ; Pregnancy ; Up-Regulation ; Zika Virus/isolation & purification ; Zika Virus Infection/metabolism ; Zika Virus Infection/pathology
Chemical Substances	Chemokine CXCL12
Language	English
Publishing date	2020-07-21
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1051484-3
ISSN	1750-3639 ; 1015-6305
ISSN (online)	1750-3639
ISSN	1015-6305
DOI	10.1111/bpa.12873
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Article ; Online: Structural characterization and polymorphism analysis of the NS2B-NS3 protease from the 2017 Brazilian circulating strain of Yellow Fever virus.

Noske, Gabriela Dias / Gawriljuk, Victor Oliveira / Fernandes, Rafaela Sachetto / Furtado, Nathalia Dias / Bonaldo, Myrna Cristina / Oliva, Glaucius / Godoy, Andre Schutzer

Biochimica et biophysica acta. General subjects

2020 Volume 1864, Issue 4, Page(s) 129521

Abstract: Background: The Yellow Fever virus (YFV) is transmitted by mosquitos and causes an infection with symptoms including fever, headaches and nausea. In 20-50% of the cases, the disease may evolve to a visceral stage, reaching high mortality rates. YFV NS2B- ...

Abstract	Background: The Yellow Fever virus (YFV) is transmitted by mosquitos and causes an infection with symptoms including fever, headaches and nausea. In 20-50% of the cases, the disease may evolve to a visceral stage, reaching high mortality rates. YFV NS2B-NS3 protease has been identified as an important drug target. Methods: Herein, we describe the crystal structure of the NS2B-NS3 protease from the 2017 YFV Brazilian circulating strain using X-ray crystallography. Furthermore, we used a combination of biochemical and biophysical assays to characterize the enzyme and investigate the impact of the polymorphisms observed in different YFV circulating strains. Results: Surprisingly, the crystal structure of YFV protease seems to adopt the closed conformation without the presence of a binding partner. Although D88E and K121R mutants exhibited a lower affinity for the substrate, both revealed to be more processive, resulting in a similar catalytic efficiency in relation to the WT protease. Still, both mutants showed an accentuated decrease in stability when compared with the WT. Conclusions: The crystal structure of YFV NS2B-NS3 in closed conformation might be an important tool for the development of new drugs, as well as understanding the activation mechanism of viral proteases. Biochemical analyses indicate that the NS2B-NS3 protease of the circulating strain of YFV is more stable than previous strains. General significance: The YFV NS2B-NS3 protease is the first flaviviral structure described in its closed conformation when in a free form, implying that external factors might induce the activation of the enzyme.
MeSH term(s)	Brazil ; Models, Molecular ; Mutagenesis, Site-Directed ; Polymorphism, Single Nucleotide/genetics ; Protein Conformation ; RNA Helicases/chemistry ; RNA Helicases/genetics ; RNA Helicases/metabolism ; Serine Endopeptidases/chemistry ; Serine Endopeptidases/genetics ; Serine Endopeptidases/metabolism ; Viral Nonstructural Proteins/chemistry ; Viral Nonstructural Proteins/genetics ; Viral Nonstructural Proteins/metabolism ; Yellow fever virus/enzymology
Chemical Substances	NS2B protein, flavivirus ; NS3 protein, flavivirus ; Viral Nonstructural Proteins ; Serine Endopeptidases (EC 3.4.21.-) ; RNA Helicases (EC 3.6.4.13)
Language	English
Publishing date	2020-01-10
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	60-7
ISSN	1872-8006 ; 1879-2596 ; 1879-260X ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1872-8006 ; 1879-2596 ; 1879-260X ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbagen.2020.129521
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Article ; Online: The yellow fever 17D virus as a platform for new live attenuated vaccines.

Bonaldo, Myrna C / Sequeira, Patrícia C / Galler, Ricardo

Human vaccines & immunotherapeutics

2014 Volume 10, Issue 5, Page(s) 1256–1265

Abstract: The live-attenuated yellow fever 17D virus is one of the most outstanding human vaccines ever developed. It induces efficacious immune responses at a low production cost with a well-established manufacture process. These advantages make the YF17D virus ... ...

Abstract	The live-attenuated yellow fever 17D virus is one of the most outstanding human vaccines ever developed. It induces efficacious immune responses at a low production cost with a well-established manufacture process. These advantages make the YF17D virus attractive as a vector for the development of new vaccines. At the beginning of vector development studies, YF17D was genetically manipulated to express other flavivirus prM and E proteins, components of the viral envelope. While these 17D recombinants are based on the substitution of equivalent YF17D genes, other antigens from unrelated pathogens have also been successfully expressed and delivered by recombinant YF17D viruses employing alternative strategies for genetic manipulation of the YF17D genome. Herein, we discuss these strategies in terms of possibilities of single epitope or larger sequence expression and the main properties of these replication-competent viral platforms.
MeSH term(s)	Animals ; Humans ; Vaccines, Attenuated/administration & dosage ; Vaccines, Attenuated/genetics ; Vaccines, Attenuated/immunology ; Yellow Fever/genetics ; Yellow Fever/immunology ; Yellow Fever/prevention & control ; Yellow Fever Vaccine/administration & dosage ; Yellow Fever Vaccine/genetics ; Yellow Fever Vaccine/immunology ; Yellow fever virus/genetics ; Yellow fever virus/immunology
Chemical Substances	Vaccines, Attenuated ; Yellow Fever Vaccine
Language	English
Publishing date	2014-02-19
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2664176-8
ISSN	2164-554X ; 2164-5515
ISSN (online)	2164-554X
ISSN	2164-5515
DOI	10.4161/hv.28117
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Article: Structural characterization and polymorphism analysis of the NS2B-NS3 protease from the 2017 Brazilian circulating strain of Yellow Fever virus

Noske, Gabriela Dias / Gawriljuk, Victor Oliveira / Fernandes, Rafaela Sachetto / Furtado, Nathalia Dias / Bonaldo, Myrna Cristina / Oliva, Glaucius / Godoy, Andre Schutzer

Biochimica et biophysica acta. 2020 Apr., v. 1864, no. 4

2020

Abstract: The Yellow Fever virus (YFV) is transmitted by mosquitos and causes an infection with symptoms including fever, headaches and nausea. In 20–50% of the cases, the disease may evolve to a visceral stage, reaching high mortality rates. YFV NS2B-NS3 protease ...

Abstract	The Yellow Fever virus (YFV) is transmitted by mosquitos and causes an infection with symptoms including fever, headaches and nausea. In 20–50% of the cases, the disease may evolve to a visceral stage, reaching high mortality rates. YFV NS2B-NS3 protease has been identified as an important drug target.Herein, we describe the crystal structure of the NS2B-NS3 protease from the 2017 YFV Brazilian circulating strain using X-ray crystallography. Furthermore, we used a combination of biochemical and biophysical assays to characterize the enzyme and investigate the impact of the polymorphisms observed in different YFV circulating strains.Surprisingly, the crystal structure of YFV protease seems to adopt the closed conformation without the presence of a binding partner. Although D88E and K121R mutants exhibited a lower affinity for the substrate, both revealed to be more processive, resulting in a similar catalytic efficiency in relation to the WT protease. Still, both mutants showed an accentuated decrease in stability when compared with the WT.The crystal structure of YFV NS2B-NS3 in closed conformation might be an important tool for the development of new drugs, as well as understanding the activation mechanism of viral proteases. Biochemical analyses indicate that the NS2B-NS3 protease of the circulating strain of YFV is more stable than previous strains.The YFV NS2B-NS3 protease is the first flaviviral structure described in its closed conformation when in a free form, implying that external factors might induce the activation of the enzyme.
Keywords	Culicidae ; X-ray diffraction ; Yellow fever virus ; catalytic activity ; crystal structure ; fever ; headache ; mortality ; mutants ; nausea ; proteinases
Language	English
Dates of publication	2020-04
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	840755-1
ISSN	0304-4165
ISSN	0304-4165
DOI	10.1016/j.bbagen.2020.129521
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