The Experts below are selected from a list of 15951 Experts worldwide ranked by ideXlab platform
Christophe N. Peyrefitte - One of the best experts on this subject based on the ideXlab platform.
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epidemic resurgence of Chikungunya Virus in democratic republic of the congo identification of a new central african strain
Journal of Medical Virology, 2004Co-Authors: Boris Pastorino, Fabienne Tock, J J Muyembetamfum, Hugues Tolou, Mael Bessaud, J P Durand, Christophe N. PeyrefitteAbstract:The resurgence of Chikungunya Virus is described during an urban epidemic in Kinshasa Democratic Republic of the Congo, after 39 years without any isolation of the Virus. Chikungunya Virus was isolated in sera from nine patients with clinical symptoms. A 1,200 bp long partial sequence of the E1/3'UTR genomic region was determined for each isolate. All sequences clustered in the central African lineage. They constitute Chikungunya Virus reference sequences for the Democratic Republic of the Congo. J. Med. Virol. 74:277–282, 2004. © 2004 Wiley-Liss, Inc.
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epidemic resurgence of Chikungunya Virus in democratic republic of the congo identification of a new central african strain
Journal of Medical Virology, 2004Co-Authors: Boris Pastorino, Fabienne Tock, J J Muyembetamfum, Hugues Tolou, Mael Bessaud, J P Durand, Christophe N. PeyrefitteAbstract:The resurgence of Chikungunya Virus is described during an urban epidemic in Kinshasa Democratic Republic of the Congo, after 39 years without any isolation of the Virus. Chikungunya Virus was isolated in sera from nine patients with clinical symptoms. A 1,200 bp long partial sequence of the E1/3'UTR genomic region was determined for each isolate. All sequences clustered in the central African lineage. They constitute Chikungunya Virus reference sequences for the Democratic Republic of the Congo.
Gorben P. Pijlman - One of the best experts on this subject based on the ideXlab platform.
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Effective Chikungunya Virus-like Particle Vaccine Produced in Insect Cells
PLOS Neglected Tropical Diseases, 2013Co-Authors: S.w.h. Metz, Lucas Y. H. Goh, Joy Gardner, Andreas Suhrbier, Just M. Vlak, Corinne Geertsema, Thuy T. Le, Gorben P. PijlmanAbstract:The emerging arthritogenic, mosquito-borne Chikungunya Virus (CHIKV) causes severe disease in humans and represents a serious public health threat in countries where Aedes spp mosquitoes are present. This study describes for the first time the successful production of CHIKV Virus-like particles (VLPs) in insect cells using recombinant baculoViruses. This well-established expression system is rapidly scalable to volumes required for epidemic responses and proved well suited for processing of CHIKV glycoproteins and production of enveloped VLPs. Herein we show that a single immunization with 1 µg of non-adjuvanted CHIKV VLPs induced high titer neutralizing antibody responses and provided complete protection against viraemia and joint inflammation upon challenge with the Reunion Island CHIKV strain in an adult wild-type mouse model of CHIKV disease. CHIKV VLPs produced in insect cells using recombinant baculoViruses thus represents as a new, safe, non-replicating and effective vaccine candidate against CHIKV infections.
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Chikungunya Virus nsp3 blocks stress granule assembly by recruitment of g3bp into cytoplasmic foci
Journal of Virology, 2012Co-Authors: Jelke J Fros, Just M. Vlak, Corinne Geertsema, Natalia E Domeradzka, Jim Baggen, Jacky Flipse, Gorben P. PijlmanAbstract:Chikungunya Virus nonstructural protein nsP3 has an essential but unknown role in alphaVirus replication and interacts with Ras-GAP SH3 domain-binding protein (G3BP). Here we describe the first known function of nsP3, to inhibit stress granule assembly by recruiting G3BP into cytoplasmic foci. A conserved SH3 domain-binding motif in nsP3 is essential for both nsP3-G3BP interactions and viral RNA replication. This study reveals a novel role for nsP3 as a regulator of the cellular stress response.
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functional processing and secretion of Chikungunya Virus e1 and e2 glycoproteins in insect cells
Virology Journal, 2011Co-Authors: Stefan W Metz, Just M. Vlak, Corinne Geertsema, Byron E E Martina, Paulina Andrade, Jacco G M Heldens, Monique M Van Oers, Rob Goldbach, Gorben P. PijlmanAbstract:Background: Chikungunya Virus (CHIKV) is a mosquito-borne, arthrogenic AlphaVirus that causes large epidemics in Africa, South-East Asia and India. Recently, CHIKV has been transmitted to humans in Southern Europe by invading and now established Asian tiger mosquitoes. To study the processing of envelope proteins E1 and E2 and to develop a CHIKV subunit vaccine, C-terminally his-tagged E1 and E2 envelope glycoproteins were produced at high levels in insect cells with baculoVirus vectors using their native signal peptides located in CHIKV 6K and E3, respectively. Results: Expression in the presence of either tunicamycin or furin inhibitor showed that a substantial portion of recombinant intracellular E1 and precursor E3E2 was glycosylated, but that a smaller fraction of E3E2 was processed by furin into mature E3 and E2. Deletion of the C-terminal transmembrane domains of E1 and E2 enabled secretion of furin-cleaved, fully processed E1 and E2 subunits, which could then be efficiently purified from cell culture fluid via metal affinity chromatography. Confocal laser scanning microscopy on living baculoVirusinfected Sf21 cells revealed that full-length E1 and E2 translocated to the plasma membrane, suggesting similar posttranslational processing of E1 and E2, as in a natural CHIKV infection. BaculoVirus-directed expression of E1 displayed fusogenic activity as concluded from syncytia formation. CHIKV-E2 was able to induce neutralizing antibodies in rabbits. Conclusions: Chikungunya Virus glycoproteins could be functionally expressed at high levels in insect cells and are properly glycosylated and cleaved by furin. The ability of purified, secreted CHIKV-E2 to induce neutralizing antibodies in rabbits underscores the potential use of E2 in a subunit vaccine to prevent CHIKV infections.
Boris Pastorino - One of the best experts on this subject based on the ideXlab platform.
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epidemic resurgence of Chikungunya Virus in democratic republic of the congo identification of a new central african strain
Journal of Medical Virology, 2004Co-Authors: Boris Pastorino, Fabienne Tock, J J Muyembetamfum, Hugues Tolou, Mael Bessaud, J P Durand, Christophe N. PeyrefitteAbstract:The resurgence of Chikungunya Virus is described during an urban epidemic in Kinshasa Democratic Republic of the Congo, after 39 years without any isolation of the Virus. Chikungunya Virus was isolated in sera from nine patients with clinical symptoms. A 1,200 bp long partial sequence of the E1/3'UTR genomic region was determined for each isolate. All sequences clustered in the central African lineage. They constitute Chikungunya Virus reference sequences for the Democratic Republic of the Congo. J. Med. Virol. 74:277–282, 2004. © 2004 Wiley-Liss, Inc.
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epidemic resurgence of Chikungunya Virus in democratic republic of the congo identification of a new central african strain
Journal of Medical Virology, 2004Co-Authors: Boris Pastorino, Fabienne Tock, J J Muyembetamfum, Hugues Tolou, Mael Bessaud, J P Durand, Christophe N. PeyrefitteAbstract:The resurgence of Chikungunya Virus is described during an urban epidemic in Kinshasa Democratic Republic of the Congo, after 39 years without any isolation of the Virus. Chikungunya Virus was isolated in sera from nine patients with clinical symptoms. A 1,200 bp long partial sequence of the E1/3'UTR genomic region was determined for each isolate. All sequences clustered in the central African lineage. They constitute Chikungunya Virus reference sequences for the Democratic Republic of the Congo.
Leen Delang - One of the best experts on this subject based on the ideXlab platform.
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simplified bryostatin analogues protect cells from Chikungunya Virus induced cell death
Journal of Natural Products, 2016Co-Authors: Daryl Staveness, Leen Delang, Johan Neyts, Rana Abdelnabi, Adam J Schrier, Brian Loy, Vishal Verma, Brian A Dechristopher, Katherine E Near, Pieter LeyssenAbstract:Chikungunya Virus (CHIKV) is a mosquito-borne alphaVirus showing a recent resurgence and rapid spread worldwide. While vaccines are under development, there are currently no therapies to treat this disease, except for over-the-counter (OTC) analgesics, which alleviate the devastating arthritic and arthralgic symptoms. To identify novel inhibitors of the Virus, analogues of the natural product bryostatin 1, a clinical lead for the treatment of cancer, Alzheimer’s disease, and HIV eradication, were investigated for in vitro antiviral activity and were found to be among the most potent inhibitors of CHIKV replication reported to date. Bryostatin-based therapeutic efforts and even recent anti-CHIKV strategies have centered on modulation of protein kinase C (PKC). Intriguingly, while the C ring of bryostatin primarily drives interactions with PKC, A- and B-ring functionality in these analogues has a significant effect on the observed cell-protective activity. Significantly, bryostatin 1 itself, a potent pan-PK...
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towards antivirals against Chikungunya Virus
Antiviral Research, 2015Co-Authors: Rana Abdelnabi, Johan Neyts, Leen DelangAbstract:Chikungunya Virus (CHIKV) has re-emerged in recent decades, causing major outbreaks of Chikungunya fever in many parts of Africa and Asia, and since the end of 2013 also in Central and South America. Infections are usually associated with a low mortality rate, but can proceed into a painful chronic stage, during which patients may suffer from polyarthralgia and joint stiffness for weeks and even several years. There are no vaccines or antiviral drugs available for the prevention or treatment of CHIKV infections. Current therapy therefore consists solely of the administration of analgesics, antipyretics and anti-inflammatory agents to relieve symptoms. We here review molecules that have been reported to inhibit CHIKV replication, either as direct-acting antivirals, host-targeting drugs or those that act via a yet unknown mechanism. This article forms part of a symposium in Antiviral Research on "Chikungunya discovers the New World."
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antiviral activity of diterpene esters on Chikungunya Virus and hiv replication
Journal of Natural Products, 2015Co-Authors: Louisfelix Nothiasscaglia, Christophe Pannecouque, Franck Renucci, Leen Delang, Johan Neyts, Fanny Roussi, Jean Costa, Pieter Leyssen, Marc Litaudon, Julien PaoliniAbstract:Recently, new daphnane, tigliane, and jatrophane diterpenoids have been isolated from various Euphorbiaceae species, of which some have been shown to be potent inhibitors of Chikungunya Virus (CHIKV) replication. To further explore this type of compound, the antiviral activity of a series of 29 commercially available natural diterpenoids was evaluated. Phorbol-12,13-didecanoate (11) proved to be the most potent inhibitor, with an EC50 value of 6.0 ± 0.9 nM and a selectivity index (SI) of 686, which is in line with the previously reported anti-CHIKV potency for the structurally related 12-O-tetradecanoylphorbol-13-acetate (13). Most of the other compounds exhibited low to moderate activity, including an ingenane-type diterpene ester, compound 28, with an EC50 value of 1.2 ± 0.1 μM and SI = 6.4. Diterpene compounds are known also to inhibit HIV replication, so the antiviral activities of compounds 1–29 were evaluated also against HIV-1 and HIV-2. Tigliane- (4β-hydroxyphorbol analogues 10, 11, 13, 15, 16, an...
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Tigliane diterpenes from Croton mauritianus as inhibitors of Chikungunya Virus replication.
Fitoterapia, 2014Co-Authors: Nina Corlay, Leen Delang, Johan Neyts, Pieter Leyssen, Emmanuelle Girard-valenciennes, Patricia Clerc, Jacqueline Smadja, Françoise Guéritte, Marc LitaudonAbstract:A bioassay-guided purification of an EtOAc extract of the leaves of Croton mauritianus using a Chikungunya Virus-cell-based assay led to the isolation of 12-O-decanoylphorbol-13-acetate (1) and the new 12-O-decanoyl-7-hydroperoxy-phorbol-5-ene-13-acetate (2), along with loliolide, vomifoliol, dehydrovomifoliol, annuionone D and bluemol C. The planar structure and the relative configuration of compound 2 were elucidated based on spectroscopic analysis, including 1D- and 2D-NMR experiments, mass spectrometry, and comparison with literature data. Compounds 1 and 2 inhibited Chikungunya Virus-induced cell death in cell culture with EC50s of 2.4±0.3 and 4.0±0.8 μM, respectively.
Johan Neyts - One of the best experts on this subject based on the ideXlab platform.
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simplified bryostatin analogues protect cells from Chikungunya Virus induced cell death
Journal of Natural Products, 2016Co-Authors: Daryl Staveness, Leen Delang, Johan Neyts, Rana Abdelnabi, Adam J Schrier, Brian Loy, Vishal Verma, Brian A Dechristopher, Katherine E Near, Pieter LeyssenAbstract:Chikungunya Virus (CHIKV) is a mosquito-borne alphaVirus showing a recent resurgence and rapid spread worldwide. While vaccines are under development, there are currently no therapies to treat this disease, except for over-the-counter (OTC) analgesics, which alleviate the devastating arthritic and arthralgic symptoms. To identify novel inhibitors of the Virus, analogues of the natural product bryostatin 1, a clinical lead for the treatment of cancer, Alzheimer’s disease, and HIV eradication, were investigated for in vitro antiviral activity and were found to be among the most potent inhibitors of CHIKV replication reported to date. Bryostatin-based therapeutic efforts and even recent anti-CHIKV strategies have centered on modulation of protein kinase C (PKC). Intriguingly, while the C ring of bryostatin primarily drives interactions with PKC, A- and B-ring functionality in these analogues has a significant effect on the observed cell-protective activity. Significantly, bryostatin 1 itself, a potent pan-PK...
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towards antivirals against Chikungunya Virus
Antiviral Research, 2015Co-Authors: Rana Abdelnabi, Johan Neyts, Leen DelangAbstract:Chikungunya Virus (CHIKV) has re-emerged in recent decades, causing major outbreaks of Chikungunya fever in many parts of Africa and Asia, and since the end of 2013 also in Central and South America. Infections are usually associated with a low mortality rate, but can proceed into a painful chronic stage, during which patients may suffer from polyarthralgia and joint stiffness for weeks and even several years. There are no vaccines or antiviral drugs available for the prevention or treatment of CHIKV infections. Current therapy therefore consists solely of the administration of analgesics, antipyretics and anti-inflammatory agents to relieve symptoms. We here review molecules that have been reported to inhibit CHIKV replication, either as direct-acting antivirals, host-targeting drugs or those that act via a yet unknown mechanism. This article forms part of a symposium in Antiviral Research on "Chikungunya discovers the New World."
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antiviral activity of diterpene esters on Chikungunya Virus and hiv replication
Journal of Natural Products, 2015Co-Authors: Louisfelix Nothiasscaglia, Christophe Pannecouque, Franck Renucci, Leen Delang, Johan Neyts, Fanny Roussi, Jean Costa, Pieter Leyssen, Marc Litaudon, Julien PaoliniAbstract:Recently, new daphnane, tigliane, and jatrophane diterpenoids have been isolated from various Euphorbiaceae species, of which some have been shown to be potent inhibitors of Chikungunya Virus (CHIKV) replication. To further explore this type of compound, the antiviral activity of a series of 29 commercially available natural diterpenoids was evaluated. Phorbol-12,13-didecanoate (11) proved to be the most potent inhibitor, with an EC50 value of 6.0 ± 0.9 nM and a selectivity index (SI) of 686, which is in line with the previously reported anti-CHIKV potency for the structurally related 12-O-tetradecanoylphorbol-13-acetate (13). Most of the other compounds exhibited low to moderate activity, including an ingenane-type diterpene ester, compound 28, with an EC50 value of 1.2 ± 0.1 μM and SI = 6.4. Diterpene compounds are known also to inhibit HIV replication, so the antiviral activities of compounds 1–29 were evaluated also against HIV-1 and HIV-2. Tigliane- (4β-hydroxyphorbol analogues 10, 11, 13, 15, 16, an...
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Tigliane diterpenes from Croton mauritianus as inhibitors of Chikungunya Virus replication.
Fitoterapia, 2014Co-Authors: Nina Corlay, Leen Delang, Johan Neyts, Pieter Leyssen, Emmanuelle Girard-valenciennes, Patricia Clerc, Jacqueline Smadja, Françoise Guéritte, Marc LitaudonAbstract:A bioassay-guided purification of an EtOAc extract of the leaves of Croton mauritianus using a Chikungunya Virus-cell-based assay led to the isolation of 12-O-decanoylphorbol-13-acetate (1) and the new 12-O-decanoyl-7-hydroperoxy-phorbol-5-ene-13-acetate (2), along with loliolide, vomifoliol, dehydrovomifoliol, annuionone D and bluemol C. The planar structure and the relative configuration of compound 2 were elucidated based on spectroscopic analysis, including 1D- and 2D-NMR experiments, mass spectrometry, and comparison with literature data. Compounds 1 and 2 inhibited Chikungunya Virus-induced cell death in cell culture with EC50s of 2.4±0.3 and 4.0±0.8 μM, respectively.
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jatrophane diterpenes as inhibitors of Chikungunya Virus replication structure activity relationship and discovery of a potent lead
Journal of Natural Products, 2014Co-Authors: Louisfelix Nothiasscaglia, Christophe Pannecouque, Johan Neyts, Fanny Roussi, Jean Costa, Pieter Leyssen, Julien Paolini, Pascal Retailleau, Vincent Dumontet, Marc LitaudonAbstract:Bioassay-guided purification of an EtOAc extract of the whole plant of Euphorbia amygdaloides ssp. semiperfoliata using a Chikungunya Virus-cell-based assay led to the isolation of six new (1–4, 9, and 10) and six known (5–7, 8, 11, and 12) jatrophane esters. Their planar structures and relative configurations were determined by extensive spectroscopic analysis, and their absolute configurations by X-ray analysis. These compounds were investigated for selective antiviral activity against Chikungunya Virus (CHIKV), Semliki Forest Virus, Sindbis Virus, and HIV-1 and HIV-2 Viruses. Compound 3 was found to be the most potent and selective inhibitor of the replication of CHIKV and of HIV-1 and HIV-2 (EC50 = 0.76, IC50 = 0.34 and 0.043 μM, respectively). A preliminary structure–activity relationship study demonstrated that potency and selectivity are very sensitive to the substitution pattern on the jatrophane skeleton. Although replication strategies of CHIK and HIV Viruses are quite different, the mechanism o...