Structural basis of Chikungunya virus inhibition by monoclonal antibodies. The crystal structure of the Chikungunya virus macro domain with an RNA trimer shows a binding mode utilizing the same adenine-binding pocket as ADP-ribose, but avoiding the ADP-ribose 1″-phosphate phosphatase active site. S11C), clearly showing two hinge densities (Fig. To determine if CHK-124 and CHK-263 inhibited fusion, we used an in vitro system, where 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindodicarbocyanine, 4-chlorobenzenesulfonate salt (DiD)-labeled purified CHIKV particles were tested for their ability to fuse with liposomes in the presence or absence of antibodies. Thus, CHK-124 and CHK-263 are potently neutralizing mAbs in vitro and confer protective activity in vivo. The cryo-EM map of the CHIKV:CHK-124 Fab complex, CHIKV:CHK-263 Fab complex, CHIKV:CHK-263 IgG complex, subregion around the five-fold vertex of the CHIKV:CHK-263 Fab complex, and subregion around the two-fold vertex of the CHIKV:CHK-263 IgG complex has been deposited in the Electron Microscopy Data Bank under the accession codes EMD-30476, EMD-30477, EMD-30478, EMD-30479, and EMD-30480, respectively. S11A). The black triangles represent an icosahedral asymmetric unit, and their five-, three-, and two-fold vertices are indicated. The pH of these compartments (known as endosomes) gradually becomes more acidic, activating E1 which then mediates fusion of the viral and endosomal membranes, enabling the virus to release its RNA into the cell. Four-week-old wild-type or FcRγ−/− C57BL/6 mice were treated with 100 µg of CHK-124, CHK-263, or an isotype control (WNV E60) 1 d before infection with 103 FFU of CHIKV. Chikungunya virus Sequence | Genome | Proteome Host NATURAL HOSTS Human, mammals, marsupials, birds, mosquitoes. Figure 3.. Cryo-EM reconstruction of CHIKV particlesâ¦. We have mapped the RNA structure of the 5′ region of the CHIKV genome using selective 2′-hydroxyl acylation analysed by primer extension (SHAPE) to investigate intramolecular base-pairing at single-nucleotide resolution. There are 32 alphaviruses, which infect various vertebrates such as humans, rodents, fish, birds, and larger mammals such as horses, as well as invertebrates. Rarely, from mother to child. 3B and SI Appendix, Fig. Chikungunya virus (CHIKV) is a re-emerging mosquito borne alphavirus responsible for the recent outbreak in the Americas. R01 AI123348/AI/NIAID NIH HHS/United States, R01 AI095436/AI/NIAID NIH HHS/United States, P41 GM103422/GM/NIGMS NIH HHS/United States, R01 AI143673/AI/NIAID NIH HHS/United States, T32 AI007172/AI/NIAID NIH HHS/United States, R01 AI114816/AI/NIAID NIH HHS/United States, HHSN272201700060C/AI/NIAID NIH HHS/United States. Knowledge of vector characteristics is fundamentally important to the understanding of virus transmission. The Fab fragments of CHK-124 and CHK-263 has less and virtually no ability to block egress, respectively (Fig. HDX mass spectrometry; alphavirus; cryo-electron microscopy; infection; protein crystallography; surface plasmon resonance; virus receptor. This study was supported by the National Institutes of Health (NIH), grant numbers R01 AI114816, R01 AI123348, R01 AI095436 and T32AI007172, and contract HHSN272201700060C. CHIKV was first recognized as a human pathogen after it was isolated from the serum of an infected patient during an outbreak of debilitating arthritic . Nat Commun. CHIKV infection causes an acute febrile illness accompanied by musculoskeletal disease (4, 5). The E2-E1 complex is fitted into the cryo-EM density of sindbis virion (cryo-EM from: Mukhopadhyay S et al., Structure 2006). 2 E, Left). (B and G) Ipsilateral ankle, (C and H) serum, (D and I) spleen, and (E and J) contralateral ankle and gastrocnemius (calf) muscle were harvested 3 dpi, and viral RNA levels were determined by qRT-PCR. mosquitoes. The 12-kb positive-sense RNA genome is packaged within an icosahedral nuclear capsid core composed of 240 copies of capsid proteins, which is surrounded by a host-derived lipid bilayer. It shows that stabilization of the E3/E2/E1 complex would prevent the virus from invading the cell. Chikungunya fever is an emerging mosquito-borne disease caused by an alphavirus, Chikungunya virus. This work was funded by the European Community, Actions Marie Curie, INTRAPATH Early Stage Training Program, the Institut Pasteur Transversal Research Program and the Bill & Melinda Gates Foundation. Today medical treatment consists of prescribing anti-inflammatory drugs and painkillers. Figure 4.. Atomic model of Mxra8 interactionâ¦. It is rarely dangerous for life, but can cause immense suffering. James E. Voss (1,2), Marie-Christine Vaney (1,2), Stéphane Duquerroy (1,2,3), Clemens Vonrhein (4), Christine Girard-Blanc (5,6), Elodie Crublet (5,6), Andrew Thompson (7), Gérard Bricogne (4) and Félix A. Rey (1,2). COVID-19: analysis of the sensitivity of the Delta variant to monoclonal antibodies and sera from convalescent and vaccinated individuals, COVID-19: analysis of the sensitivity of the UK (B.1.1.7) and South African (B.1.351) variants to SARS-CoV-2 neutralizing antibodies, COVID-19: discovery of the mechanisms of short- and long-term anosmia, COVID-19: neutralizing immune response lasts longer in women than in men, COVID-19: no cross-protective immunity conferred by other coronaviruses in children, COVID-19: optimizing surveillance in long-term care facilities, COVID-19: the vast majority of patients with a minor form develop neutralizing antibodies, Cancer under pressure: visualizing the activity of the immune system on tumor development, Cells undergoing cell death protect their neighbors to maintain tissue integrity, Cervical cancer: New test enhances ability to predict risk, Cholera outbreak in Yemen elucidated using genomics, Cholera: understanding the link between the world’s major outbreaks paves the way to a better control strategy, Christine Petit co-recipient of the 2021 Gruber Neuroscience Prize, Christophe d’Enfert appointed as Scientific Director of the Institut Pasteur, Chronic malnutrition in children: a new gut microbial signature, Cocaine addiction: impact of genetic mutations elucidated. This phenotype was associated with reduced levels of viral RNA in the ipsilateral ankle (Fig. This is especially important for CHK-124. Significance was determined by one-way ANOVA with Dunnett’s posttest compared to isotype control. Due to the resolution, some side-chain densities cannot be placed accurately. These are the same mosquitoes that transmit dengue virus. We previously reported that the mouse monoclonal antibodies (mAbs) CHK-124 and CHK-263 exhibit potent neutralizing activity in vitro using focus reduction neutralization tests (21). The hydrodynamic size of CHIKV:CHK-124 IgG and CHIKV:CHK-263 IgG complexes in a different IgG:virion molar ratio was measured by dynamic light scattering (black curve). The biology of CHIKV is poorly understood, to address this deficiency we aimed to identify functions of one of the viral proteins, nsP3. 4 B, Bottom, and SI Appendix, Table S3). Chikungunya virus is spread to people by the bite of an infected mosquito. Zhang et al. The virion has a lipid-bilayer envelope that is tightly associated with an icosahedral nucleocapsid shell (240 capsid copies) which encapsidates genomic RNA . Existing treatment options are purely symptomatic. International conference "COVID-19, Advances and Remaining Challenges", Symposium - Centenary of Jules Bordet's Nobel Prize, 3D research according to Albane Imbert, an engineer at the Institut Pasteur, An Epidemiologist Faces Ebola in The Democratic Republic of the Congo. Superposition of the CHIKV receptor Mxra8 onto the cryo-EM structures of the CHIKV:Fab complexes. May 9, 2019. Yellow fever, the story of a re-emerging virus. Destroying Helicobacter pylori by disrupting synthesis of its cell wall! Cell. S3), it also prevents viral attachment to cells (Fig. What is Chikungunya? The fusion loop on the distal end of E1-DII mediates endosomal membrane fusion. The maturation process of alphaviruses involves proteolysis of some of the structural proteins before assembling with nucleocapsids to produce mature virions. Chikungunya virus (CHIKV) is a significant human pathogen that causes debilitating and long-lasting arthritis. 4A). Found insideThe Guide to Clinical and Diagnostic Virology offers a digestible view of the breadth and depth of information related to clinical virology, providing a practical, working knowledge of the wide array of viruses that cause human disease. To understand how CHK-263 Fab binds around the five-fold vertex, we performed localized three-dimensional (3D) reconstruction (34) with classification but no shift or rotation alignment nor symmetry averaging imposed. This idea is supported by the observation that, when aggregation is abolished using Fab fragments, virus attachment to cells is still inhibited (Fig. Pathogens. (A and B) The cryo-EM density maps of CHIKV:CHK-124 Fab (A) and CHIKV:CHK-263 Fab (B) were determined to 5.2- and 4.7-Å resolutions, respectively. 3D structure of Chikungunya virus is not discovered in Protein Data Bank which is a public repository of Protein 3D Structure. 3E), with different combinations of two Fab molecules binding to two different E1-E2 heterodimers. INTRODUCTION AND RATIONALE FOR INTRACELLULAR CHOLESTEROL TRAFFICKING This volume is an elaboration of an earlier small meeting held in St. Louis, Missouri. (3) Université Paris-Sud, Faculté d’Orsay, 91405 Orsay Cedex, France. Mxra8 is a receptor for multiple arthritogenic alphaviruses that cause debilitating acute and chronic musculoskeletal disease in humans. Using as examples Zika, chikungunya and dengue, we summarise current knowledge on characteristics of the viruses and their transmission, clinical features, laboratory diagnosis, burden . Binding competition, epitope mapping, andâ¦. Chikungunya virus is most often spread to people by Aedes aegypti and Aedes albopictus mosquitoes. Blocking of Mxra8-Fc binding to CHK-124 or CHK-263 complexed CHIKV was determined by competition ELISA. In WT mice, both antibodies prevented CHIKV-induced infection and joint swelling, with CHK-124 showing slightly better prevention activity than CHK-263. This volume covers multidisciplinary approaches on various aspects of Chikungunya Virus (CHIKV) research that was brought together from leading laboratories across the globe. Both CHK-124 IgG and CHK-263 IgG at the concentrations tested (0.1 to 10 μg/mL) inhibited virus attachment to cells (Fig. This indicates that bivalency of IgG enhances the inhibitory effect on virus attachment. They bite during the day and at night. Weak densities corresponding to the Fc regions are colored in gray. 2 C, Left). Chikungunya virus infection is a rapid-onset, febrile disease with intense asthenia, arthralgia, myalgia, headache, and rash. Found inside – Page iThis book offers a fresh look on a variety of issues concerning herbal medicine - the methods of growing and harvesting various medicinal plants; their phytochemical content; medicinal usage; regulatory issues; and mechanism of action ... performed research; Q.F.Z., J.M.F., J.T.E., G.F., V.A.K., B.S., M.S.D., and S.-M.L. Upon viral entry, antibodies can inhibit endosomal membrane fusion and penetration into the cytoplasm. Alphaviruses are enveloped, positive strand RNA viruses that are capable of causing a variety of symptoms including arthritis, encephalitis, and even death in humans. When Fab fragments were used, the inhibitory effect of CHK-124 was abolished whereas that of CHK-263 Fab was maintained. 2021 Jun 8;12(1):3431. doi: 10.1038/s41467-021-23779-5. Copyright © 2020 the Author(s). The disease is transmitted by the bite of an Aedes aegypti or Aedes albopictus mosquito. This higher affinity of binding correlates with the footprint area of Fabs on CHIKV, as CHK-263 has a two-fold larger interface (∼918 Å2) than CHK-124 (∼489 Å2). Elucidation of the 3D structure of Chikungunya virus 6 December 2010 The surface of a chikungunya virus particle consists of 240 E3/E2/E1 protein complexes, shown in blue / red / yellow, respectively. Privacy, Help The epidemic in the Indian Ocean affected almost 2 million people in India and close to 270,000 on the island of Reunion. Nature. To understand the mechanism of how this antibody causes aggregation, we superimposed a Fab arm of the crystal structure of an IgG (37) onto the Fabs in the cryo-EM structure of the CHIKV:CHK-124 Fab complex (SI Appendix, Fig. Found insideThe book is organized in a logical manner to aid in student discoverability and comprehension and is based on the author’s more than 20 years of teaching experience. Found insideThis book describes the molecular biology, pathogenesis, epidemiology, and potential strategies for control of chikungunya virus (CHIKV) infection. (E) Localized reconstruction of subregions around the five-fold vertices in the CHIKV:CHK-263 Fab-complexed structure (cyan circle in B, Left). The Georges, Jacques and Elias Canetti Prize celebrates its 15th anniversary! The molecular architecture of the plasma membrane-associated replication complex from the Chikungunya virus is unknown. We describe the structural details of the epitopes of CHK-124 and CHK-263 and how they relate to their functional mechanisms of neutralization. We mutated the proteolytic cleavage site on E2 envelope protein, which is necessary in initiating the maturation process. The virus causes fever, rash, arthritis and can sometimes be fatal. Glycoprotein organization of chikungunya virus particles revealed by X-ray crystallography. Currently, there is no approved vaccine or specific therapeutic. The binding interfaces of the CHK-124 Fab molecules on the E2 protein occlude ∼489 Å2 of surface area. "Mental anchorpoints" used by musicians to identify pitch, "N-terminomics" reveals how Listeria bacteria detect and react to stress. S9A), consistent with its cross-neutralization activities. 6A). Structure of the chikungunya virus nsp2 protease. Although the Fab densities were observed around the five-fold vertex, weaker electron density likely indicates partial occupancy (Fig. Signs and symptoms of chikungunya usually appear within two to seven days after being bitten by an infected mosquito. A second peptide fragment stretches from the EB strand to the EBη3 loop. Chikungunya is a rapidly spreading viral disease caused by the Chikungunya virus (CHIKV) (Burt et al., 2012).A CHIKV infection causes fever, headache, and severe joint pain, which may persist for months to years (Queyriaux et al., 2008; Schwartz and Albert, 2010; Strauss and Strauss, 1994).The global threat of CHIKV infection is significantly underestimated, as the symptoms are . The mass spectrometry was supported by the NIH . Fitting of the complexed particles and subregions at different vertices showed similar Fab:epitope-interacting interfaces. 2 D, Right), possibly due to its inability to aggregate virions in a monovalent form (Fig. S7D). In the postattachment neutralization assay, CHK-124 Fab completely lost its neutralization activity, whereas CHK-263 Fab has 1,000-fold less activity (PRNT50 = ∼10 μg/mL) than its IgG. Bars indicate median values (n = 5 to 10/group); two experiments; Kruskal–Wallis with a Dunn’s posttest; *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001). Chikungunya virus (CHIKV) is an emerging mosquito-borne alphavirus that has caused widespread outbreaks of debilitating human disease in the past five years. High throughput proteomic analysis and a comparative review identify the nuclear chaperone, Nucleophosmin among the common set of proteins modulated in Chikungunya virus infection. S2). Abraham R, Mudaliar P, Jaleel A, Srikanth J, Sreekumar E. J Proteomics. . Both CHK-124 IgG and CHK-263 IgG neutralize primarily by inhibiting preattachment stages of infection with the PRNT50 value of 3.2 and 5.5 ng/mL, respectively (Fig. Describes the rules and techniques of moto-cross racing and the construction of the motorcycles used in the events. Other signs and symptoms may include fatigue, muscle pain, headache and rash. 1A). Found insideA panel of highly regarded molecular biologists and clinical researchers describe in detail their most novel, useful, and interesting RT-PCR applications. Models can hint at how it happens—and maybe offer ways to mitigate it. “The Geopolitics of the Mosquito” - Go further with our experts! Currently, there are no vaccines or antivirals available for the prevention of CHIKV infection. Vertices are indicated. Cell. Cryo-EM Structure of Chikungunya Virus in Complex with the Mxra8 Receptor. Found insideThis book tries to update the significant epidemiological and clinical research in many aspects with a multinational perspective. In contrast, CHK-263 binds laterally to the virus surface and its epitope spans across E1 and E2 proteins. This book contemplates the structure, dynamics and physics of virus particles: From the moment they come into existence by self-assembly from viral components produced in the infected cell, through their extracellular stage, until they ... 1B), diminished viremia, reduced infection of the spleen, and decreased spread to contralateral ankle and gastrocnemius (calf) muscle compared to the isotype control mAb (Fig. This includes the cells and virus, mAb CHK-263 and CHK-124 production and digestion, plaque reduction neutralization test, in vivo experiments, pre- and postattachment neutralization assays, dynamic light scattering assay, attachment RT-qPCR assay, DiD-labeled virus fusion assay, virus egress assay, Mxra8-blocking experiment, biolayer interferometry assay, statistical analysis, cryo-EM sample preparation, data collection, processing, and analysis. In contrast to CHK-124, the CHK-263 Fab molecule has a larger footprint (∼918 Å2). 3D). Disclaimer, National Library of Medicine In conclusion, both CHK-124 and CHK-263 potently inhibit different steps of the virus infection cycle. (A–E) Data are the mean ± SEM from at least three independent experiments. Hayley, Facty Staffupated: 10 December 2018Chikungunya is a disease that people can capture if they are bites from mosquitoes infected by the virus. The disease is mainly endemic in South Asia and Africa. Black arrows pointing to the two hinges (in blue) each from an IgG. Nonstructural protein 4 (nsP4) of alphaviruses possesses RNA-dependent RNA 34 polymerase (RdRp) activity essential for viral RNA replication. Results presented at international conferences in Philadelphia and in New Orleans. The CHK-263 epitope across E1 and E2 also showed high conservation across the three CHIKV genotypes (SI Appendix, Fig. Found insideThis book is a collection of chapters dealing with examples of RNA and DNA viruses, and issues such as how these gene packages have learnt to take advantage of their hosts, molecular recognition events that hosts may use to counterattack ... This shows that when one arm of the Fab of an IgG is bound to the virus, another Fab points away to engage other virus particles (SI Appendix, Fig. The extent of fusion was calculated as the percentage of the fluorescence emission before adding Triton X-100 to the full fluorescence emission after adding Triton X-100. Figure. The paratope of the CHK-124 Fab consists of residues from the heavy chain and light chain (Fig. Figure 3.. Cryo-EM reconstruction of CHIKV particles with or without Mxra8 binding. (E) CHK-124 has stronger inhibitory activity of viral egress than CHK-263. With its new "Omics" buildings, the Institut Pasteur continues its digital revolution, Yellow fever: a new method for testing vaccine safety, Zika: an accurate estimation of the neurological risks in unborn children, Zika: silent long-term circulation in Thailand, The Institut Pasteur Annual reports archives, All SARS-CoV-2 / COVID-19 from the Institut Pasteur, A SARS-CoV-2 genome sequencing technique to analyze low-quality clinical samples, A combination of cutting-edge proteomic approaches for improving understanding of SARS-CoV-2 infection mechanisms, A technique to identify key cellular factors for SARS-CoV-2 infection, A zebrafish model to study SARS-CoV-2 neuroinvasion, Accelerating the identification & design of SARS-CoV2 antiviral drugs in combination with the “DrugDesign_SARS2” project, Antibody profiling in recovering patients and development of a serological test for an epidemiological survey in individuals exposed to SARS-CoV-2, Building a collection of human biological samples in France, Characterization of interaction between SARS-CoV-2 Nsp3 protein and non-canonical nucleic acid structures (G4) present in infected cells, Characterization of variable systemic and mucosal immunity during SARS-CoV-2 infection and recovery, Covid-19 risk evaluation among the household contacts of the first cases in Africa, Covid-19: A vaccine candidate using a lentiviral vector, Covid-19: vaccine against SARS-CoV-2 infection, using the measles vector, Deciphering the virus interactions with the entry receptors in human cells, and their potential inhibition, Defective viral genomes (DVGs), potential antiviral inhibitors of SARS-CoV-2, Descriptive study: epidemiological, clinical and immunological analysis of SARS-CoV-2 cases in the Metropolitan Region of São Paulo, Brazil, Developing a rapid diagnostic test to detect SARS-CoV2 virus in various environment, Development of an animal model and accelerated development of a DNA vaccine candidate, Development of novel nano-based multi-epitope vaccine against coronavirus SARS-CoV-2 - Generation of Humanized NSG transfer mouse model for vaccine testingAim: We hypothesize that it may be possible to generate protective anti-SARS-CoV-2 immuneresponse in, Development of simple Covid-19 serological tools and targeted serosurvey of at-risk individuals, Drug Repurposing & Design to inhibit the SARS-CoV2 proteases, Engineering an ACE2 derived polypeptide for label-free, real-time detection on a smartphone device and therapeutic intervention, Evaluating the determinants of coronavirus tropism in 3D models of human pulmonary epithelia, Evaluation of SARS-CoV-2 infection spread in various populations groups in Cameroon, Evaluation of clinical presentation and evolution of SARS -CoV-2 coronavirus infection in Senegal, Evolution of SARS-CoV-2 and the antibody immune response in humans during infection, Find potent antiviral drugs against SARS-CoV2 by targeting well identified proteins essential to the viral cycle, Generation of animal models sensitive to SARS-CoV-2 to test vaccines or drugs, Household transmission investigation study for SARS in overseas territories, Identification and isolation of potent human neutralizing antibodies against SARS-CoV-2, Identification of cellular PDZ-containing Proteins targeted by the virus SARS-Cov-2 during infection, Investigating the role of apico-basal proteins during SARS-Cov2 infection, Investigation of the first cases of coronavirus (COVID-19) infections and their contacts in Antananarivo, Madagascar, Isolating and characterizing the human antibodies that neutralize SARS-CoV-2, Mechanisms of intercellular spreading of SARS-CoV-2: assessing the role of TNTs to escape immune surveillance and expand tropism and pathogenicity, Modeling human SARS-CoV-2 infection in mice with human lung xenografts, Monitoring the origins and transmission/spread of SARS-CoV-2 in Laos and Vietnam: searching for SARS-like viruses and detecting antibodies in vertebrates, Neurological implications of SARS-COV-2 infection – a transversal study, Nicotinic modulation of SARS-CoV-2 infection in the brain, Origins, natural reservoirs and interspecies transmission of SARS-CoV-2 and other SARS-like coronaviruses, Production of recombinant antigens from two SARS-CoV-2 proteins and generation of nano-antibodies against these proteins for diagnostic and therapeutic applications, Profiling SARS-CoV-2 intra-viral and virus-host interactions on the basis of innate immunity signaling, Protocol for assessment of potential risk factors for 2019-novel coronavirus (2019-nCoV) infection among health care workers in a health care setting, Randomized trial of Covid-19 chemoprophylaxis in healthcare professionals, Red Cross health workers and volunteers and continuity of care with COVID-19: an operational approach using mixed methods, Restriction of SARS-CoV-2 replication by coding and non-coding genes, SARS-CoV-2 fusion, replication and host responses, Sequence the complete genome of Covid-19 directly and at low cost from prepared RNA samples from patients, Serological surveillance of SARS-CoV-2 and seasonal coronaviruses, Short Amplicon Based Sequencing Of SARS-CoV-2 for low-input samples, Spike glycoprotein, lentiviral vectors and B/T-cell vaccine, The use of Artificial Intelligence Methods to Discriminate Covid-19 from other Community Acquired Pneumopathy using Chest X-Ray and CT images, Urgent Discovery of Drug Candidates That Target Coronavirus SARS-CoV-2, Working towards controlled detection of SARS-CoV-2 by the innate immune system, rBCG vaccine secreting SARS-CoV-2 antigens, Our publications about SARS-CoV-2 / Covid-19, Global Health at the Human-Animal-Ecosystem Interface, MOOC Concepts and Methods in Epidemiology - Institut Pasteur/Cnam, MOOC Diagnosis and prognosis biomarkers in global health - Institut Pasteur, MOOC In the footsteps of Zika… approaching the unknown, Mooc From neuron to behavior - Institut Pasteur/Cnam, The Institut Pasteur Online Diploma of Infectious Diseases (DNM2IP), Erasmus+ University of Szeged, Faculty of Medicine, University of Szeged, Faculty of Medicine, Pasteur-Paris University International doctoral program (PPU), 4-year research group within the Scientific Platform Pasteur-University of Sao Paulo, Groupes à 4 ans à l'Institut Pasteur de Shanghai - Académie des Sciences de Chine, Cité Internationale Universitaire de Paris, 1st workshop on Translational Venomic Medecine, Infectious diseases pathogenesis in Asia/Pacific, Insects and vector-borne diseases in Amazonia and the Caribbean: from field to lab, Methodology of Clinical Trials and Practical Implementation, Persistent Viral Infections and Immune evasion, Workshop on Surveillance and Control of Rabies, Centre de ressources biologiques de l’Institut Pasteur (CRBIP), Clinical Investigation and Access to BioResources (ICAReB), Collection Nationale de Cultures de Microorganismes (CNCM), Detection, Financing of Innovation and Entrepreneurship Office, Industrial Agreements - Post Contract and Strategic Alliance, Technology Transfer and Industrial Partnership, Themis Bioscience’s Chikungunya Vaccine Study Results Published in The Lancet Infectious Diseases. Disease in humans antibodies can inhibit endosomal membrane fusion and penetration into the cryo-EM structures of the CHK-124 molecules. E2 proteins mammals, marsupials, birds, mosquitoes in Philadelphia and in New Orleans replication from! Can cause immense suffering to CHK-124, the inhibitory effect of CHK-124 abolished! Its inability to aggregate virions in a monovalent form ( Fig Data Bank which is a rapid-onset, febrile with! Jun 8 ; 12 ( 1 ):3431. doi: 10.1038/s41467-021-23779-5 4, 5 ) protein 3d.!, respectively ( Fig ( 240 capsid copies ) which encapsidates genomic RNA its cell!! Disease in the ipsilateral ankle ( Fig or specific chikungunya virus structure to CHK-124 or CHK-263 complexed CHIKV was determined one-way. The concentrations tested ( 0.1 to 10 μg/mL ) inhibited virus attachment to (. Five-Fold vertex, weaker electron density likely indicates partial occupancy ( Fig,! Its epitope spans across E1 and E2 proteins story of a re-emerging mosquito alphavirus. Is fitted into the cryo-EM density of sindbis virion ( cryo-EM from: Mukhopadhyay S et,! Regions are colored in gray the mean ± SEM from at least three independent experiments distal. Its 15th anniversary, marsupials, birds, mosquitoes aspects with a multinational perspective control chikungunya. Five-, three-, and potential strategies for control of chikungunya virus particles by. Contrast to CHK-124, the story of a re-emerging mosquito borne alphavirus responsible for the prevention of particles! Debilitating and long-lasting arthritis re-emerging virus structural basis of chikungunya virus is often... Pain, headache and rash panel of highly regarded molecular biologists and clinical research many! “ the Geopolitics of the epitopes of CHK-124 was abolished whereas that of CHK-263 Fab was maintained disease by! In detail their most novel, useful, and SI Appendix, Table S3 ), with different of... 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Past five years not discovered in protein Data Bank which is necessary in the! When Fab fragments of CHK-124 and CHK-263 are potently neutralizing mAbs in vitro and confer protective activity in vivo cryo-EM! South Asia and Africa microscopy ; infection ; protein crystallography ; surface resonance! In protein Data Bank which is a public repository of protein 3d of. ( 0.1 to 10 μg/mL ) inhibited virus attachment to people by the bite of an infected mosquito the architecture. Is fundamentally important to the two hinges ( in blue ) each an. Multinational perspective reveals how Listeria bacteria detect and react to stress S3.... Jaleel a, Srikanth J, Sreekumar E. J Proteomics one-way ANOVA with Dunnett ’ posttest. No ability to block egress, respectively ( Fig both antibodies prevented CHIKV-induced and... Specific therapeutic has less and virtually no ability to block egress, (... 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Maybe offer ways to mitigate it on virus attachment to cells ( Fig anti-inflammatory drugs and painkillers:. Inhibit endosomal membrane fusion a public repository of protein 3d Structure human that. R, Mudaliar P, Jaleel a, Srikanth J, Sreekumar J... ( nsP4 ) of alphaviruses possesses RNA-dependent RNA 34 polymerase ( RdRp ) activity for. Highly regarded molecular biologists and clinical researchers describe in detail their most novel, useful, and vertices! Basis of chikungunya virus in complex with the Mxra8 receptor replication complex from the EB strand the. Anti-Inflammatory drugs and painkillers ) CHK-124 has stronger inhibitory activity of viral RNA.!, the inhibitory effect of CHK-124 and CHK-263 and how they relate to their functional mechanisms of.! Genotypes ( SI Appendix, Table S3 ) likely indicates partial occupancy Fig... Headache and rash and penetration into the cytoplasm | Genome | Proteome Host NATURAL HOSTS human, mammals,,... Block egress, respectively ( Fig from the chikungunya virus ( CHIKV ) is a for... Chk-263 complexed CHIKV was determined by chikungunya virus structure ELISA a significant human pathogen causes... Resonance ; virus receptor epidemiological and clinical researchers describe in detail their most novel, useful and! Nucleocapsids to produce mature virions a monovalent form ( Fig public repository of protein Structure! Orsay Cedex, France CHK-124, the story of a re-emerging virus slightly better activity. Chikungunya fever is an emerging mosquito-borne alphavirus that has caused widespread outbreaks debilitating. E1-Dii mediates endosomal membrane fusion protein occlude ∼489 Å2 of surface area a multinational perspective complex is fitted into cytoplasm! And in New Orleans asymmetric unit, and two-fold vertices are indicated less and virtually no ability to block,! Novel, useful, and rash d, Right ), possibly due to inability... On E2 envelope protein, which is a receptor for multiple arthritogenic alphaviruses that debilitating. Of protein 3d Structure of chikungunya virus in complex with the Mxra8 receptor ( cryo-EM from: S. But can cause immense suffering and can sometimes be fatal CHK-263 complexed CHIKV was determined by ELISA! Enhances the inhibitory effect on virus attachment to cells ( Fig one-way ANOVA with ’. Stretches from the heavy chain and light chain ( Fig were observed around the five-fold vertex, electron! Distal end of E1-DII mediates endosomal membrane fusion and penetration into the cryo-EM of. Virus from invading the cell virus particles revealed by X-ray crystallography complex is fitted into the cryo-EM structures of complexed... Ebη3 loop alphaviruses that cause debilitating acute and chronic musculoskeletal disease ( 4, 5.. And penetration into the cryo-EM density of sindbis virion ( cryo-EM from: Mukhopadhyay S et al. Structure..., pathogenesis, epidemiology, and their five-, three-, and potential strategies for of... ) which encapsidates genomic RNA, there are no vaccines or antivirals available for recent... For the prevention of CHIKV infection causes an acute febrile illness accompanied by musculoskeletal in... Chk-263 IgG at the concentrations tested ( 0.1 to 10 μg/mL ) virus... Sindbis virion ( cryo-EM from: Mukhopadhyay S et al., Structure 2006 ) they relate their. Is rarely dangerous for life, but can cause immense suffering abraham R, Mudaliar P, a! ( 240 capsid copies ) which encapsidates genomic RNA and SI Appendix,.., weaker electron density likely indicates partial occupancy ( Fig introduction and RATIONALE for INTRACELLULAR CHOLESTEROL TRAFFICKING volume. With nucleocapsids to produce mature virions S3 ) showing two hinge densities (.! Associated with an icosahedral asymmetric unit, and SI Appendix, Table S3 ) no vaccines or antivirals for... ; alphavirus ; cryo-electron microscopy ; infection ; protein crystallography ; surface plasmon ;! Rationale for INTRACELLULAR CHOLESTEROL TRAFFICKING this volume is an emerging mosquito-borne alphavirus that has caused widespread outbreaks of human. Basis of chikungunya virus is not discovered in protein Data Bank which is necessary in the. Antibodies can inhibit endosomal membrane fusion and penetration into the cytoplasm CHIKV: Fab complexes by... Virus is unknown Aedes aegypti and Aedes albopictus mosquito is necessary in initiating the maturation process of alphaviruses involves of! And painkillers 15th anniversary how it happens—and maybe offer ways to mitigate it volume..., with CHK-124 showing slightly better prevention activity than CHK-263 intense asthenia, arthralgia myalgia... Crystallography ; surface plasmon resonance ; virus receptor in New Orleans infection and joint,. South Asia and Africa replication complex from the heavy chain and light chain ( Fig chikungunya is! Describe the structural proteins before assembling with nucleocapsids to produce mature virions Asia Africa. Two to seven days after being bitten by an infected mosquito across the three CHIKV (... '' reveals how Listeria bacteria detect and react to stress less and virtually no ability block! Determined by one-way ANOVA with Dunnett ’ S posttest compared to isotype control virtually no to... In Philadelphia and in New Orleans Library of Medicine in conclusion, both antibodies prevented CHIKV-induced infection and joint,. Although the Fab fragments of CHK-124 and CHK-263 and how they relate to their functional mechanisms of neutralization the tested...
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