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D.w. Smith - One of the best experts on this subject based on the ideXlab platform.
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Long term outcomes of Murray Valley Encephalitis cases in Western Australia - what have we learnt?
Internal medicine journal, 2016Co-Authors: Linda A. Selvey, David J. Speers, D.w. SmithAbstract:Background: Murray Valley Encephalitis virus (MVEV) is a mosquito-borne flavivirus that causes Encephalitis in some cases of infection. It is endemic in Northern Australia and cases occasionally occur in South Eastern Australia. The long-term sequelae of MVEV infection have not previously been well described. Aim: To investigate the long-term sequelae of MVEV infection. Methods: This was a descriptive case series of all clinical MVEV infections using data linkage and standard surveys. Hospital admissions, emergency department, psychiatric outpatients and mortality data were obtained. We attempted to follow-up all 53 cases of MVEV clinical infection that occurred in Western Australia from 1978 to 2011 inclusive. Two cases opted out of the study. Results: We followed-up 39 surviving cases. Seven of the nine with paralysis or paresis were under 5years and they fared worse than other patients, requiring lengthy hospitalisation (median duration 133days). Two died due to complications of quadriplegia following a total of 691days in hospital. Nine surviving patients, including two with non-encephalitic illness, required care for depression and other psychiatric conditions following MVEV infection. Two patients who were discharged with neurological sequelae had no further documented hospital occasions of service but reported ongoing challenges with cognitive dysfunction and inability to work. Conclusions: This is the first study of long-term outcomes of Murray Valley Encephalitis that included cases with no obvious sequelae at discharge. In spite of the small numbers involved, the study demonstrated the significant medical and social burden due to MVEV in Australia.
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Clinical and radiological predictors of outcome for Murray Valley Encephalitis.
The American journal of tropical medicine and hygiene, 2013Co-Authors: David J. Speers, James Flexman, Christopher C. Blyth, Nirooshan Rooban, Edward Raby, Ganesh Ramaseshan, Susan Benson, D.w. SmithAbstract:Abstract. A review of the laboratory-confirmed cases of Murray Valley Encephalitis (MVE) from Western Australia between 2009 and 2011 was conducted to describe the clinical, laboratory, and radiological features of the disease. The nine Encephalitis patients presented with altered mental state and seizures, tremor, weakness, or paralysis. All patients developed a raised C-reactive protein, whereas most developed acute liver injury, neutrophilia, and thrombocytosis. All patients with Encephalitis developed cerebral peduncle involvement on early magnetic resonance imaging (MRI). The absence of thalamic MRI hyperintensity during the acute illness, with or without leptomeningeal enhancement, predicted a better neurological outcome, whereas those patients with widespread abnormalities involving the thalamus, midbrain, and cerebral cortex or the cerebellum had devastating neurological outcomes. MRI scans repeated months after acute illness showed destruction of the thalamus and basal ganglia, cortex, or cerebellum. These findings may help clinicians predict the neurological outcome when evaluating patients with MVE.
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Murray Valley Encephalitis: a review of clinical features, diagnosis and treatment
The Medical journal of Australia, 2012Co-Authors: James Knox, John S. Mackenzie, Bart J. Currie, Raquel U Cowan, Joseph Doyle, Matthew K Ligtermoet, John S. Archer, James Burrow, Steven Y. C. Tong, D.w. SmithAbstract:Murray Valley Encephalitis virus (MVEV) is a mosquito-borne virus that is found across Australia, Papua New Guinea and Irian Jaya. MVEV is endemic to northern Australia and causes occasional outbreaks across south-eastern Australia. 2011 saw a dramatic increase in MVEV activity in endemic regions and the re-emergence of MVEV in south-eastern Australia. This followed significant regional flooding and increased numbers of the main mosquito vector, Culex annulirostris, and was evident from the widespread seroconversion of sentinel chickens, fatalities among horses and several cases in humans, resulting in at least three deaths. The last major outbreak in Australia was in 1974, during which 58 cases were identified and the mortality rate was about 20%. With the potential for a further outbreak of MVEV in the 2011-2012 summer and following autumn, we highlight the importance of this disease, its clinical characteristics and radiological and laboratory features. We present a suspected but unproven case of MVEV infection to illustrate some of the challenges in clinical management. It remains difficult to establish an early diagnosis of MVEV infection, and there is a lack of proven therapeutic options.
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Genetic and phenotypic differences between isolates of Murray Valley Encephalitis virus in Western Australia, 1972–2003
Virus Genes, 2007Co-Authors: Cheryl A. Johansen, Roy A. Hall, John S. Mackenzie, D.w. Smith, Veronica Susai, David C. Clark, Fiona J. May, Stéphane Hemmerter, Annette K. BroomAbstract:Murray Valley Encephalitis virus (MVEV) is a medically important mosquito-borne flavivirus found in Australia and Papua New Guinea (PNG). Partial envelope gene nucleotide sequences of 28 isolates of MVEV from Western Australia (WA) between 1972 and 2003 were aligned and compared phylogenetically with the prototype MVE-1-51 from Victoria in 1951 and isolates from northern Queensland and PNG. Monoclonal antibody-binding patterns were also investigated. Results showed that the majority of isolates of MVEV from widely disparate locations in WA were genetically and phenotypically homogeneous. Furthermore, isolates of MVEV from WA and northern Queensland were almost identical, confirming results from earlier studies. Recent isolates of MVEV from Western Province in PNG were more similar to Australian isolates of MVEV than to isolates from PNG in 1956 and 1966, providing further evidence for the movement of flaviviruses between PNG and Australia. Additional representatives of a unique variant of MVEV (OR156) from Kununurra in the northeast Kimberley region of WA were also detected. This suggests that the OR156 lineage is still intermittently active but may be restricted to a small geographic area in northern WA, possibly due to altered biological characteristics.
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genetic and phenotypic differences between isolates of Murray Valley Encephalitis virus in western australia 1972 2003
Virus Genes, 2007Co-Authors: Cheryl A. Johansen, Roy A. Hall, D.w. Smith, J S Mackenzie, Veronica Susai, David C. Clark, Fiona J. May, Stéphane Hemmerter, A K BroomAbstract:Murray Valley Encephalitis virus (MVEV) is a medically important mosquito-borne flavivirus found in Australia and Papua New Guinea (PNG). Partial envelope gene nucleotide sequences of 28 isolates of MVEV from Western Australia (WA) between 1972 and 2003 were aligned and compared phylogenetically with the prototype MVE-1-51 from Victoria in 1951 and isolates from northern Queensland and PNG. Monoclonal antibody-binding patterns were also investigated. Results showed that the majority of isolates of MVEV from widely disparate locations in WA were genetically and phenotypically homogeneous. Furthermore, isolates of MVEV from WA and northern Queensland were almost identical, confirming results from earlier studies. Recent isolates of MVEV from Western Province in PNG were more similar to Australian isolates of MVEV than to isolates from PNG in 1956 and 1966, providing further evidence for the movement of flaviviruses between PNG and Australia. Additional representatives of a unique variant of MVEV (OR156) from Kununurra in the northeast Kimberley region of WA were also detected. This suggests that the OR156 lineage is still intermittently active but may be restricted to a small geographic area in northern WA, possibly due to altered biological characteristics.
Annette K. Broom - One of the best experts on this subject based on the ideXlab platform.
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Genetic and phenotypic differences between isolates of Murray Valley Encephalitis virus in Western Australia, 1972–2003
Virus Genes, 2007Co-Authors: Cheryl A. Johansen, Roy A. Hall, John S. Mackenzie, D.w. Smith, Veronica Susai, David C. Clark, Fiona J. May, Stéphane Hemmerter, Annette K. BroomAbstract:Murray Valley Encephalitis virus (MVEV) is a medically important mosquito-borne flavivirus found in Australia and Papua New Guinea (PNG). Partial envelope gene nucleotide sequences of 28 isolates of MVEV from Western Australia (WA) between 1972 and 2003 were aligned and compared phylogenetically with the prototype MVE-1-51 from Victoria in 1951 and isolates from northern Queensland and PNG. Monoclonal antibody-binding patterns were also investigated. Results showed that the majority of isolates of MVEV from widely disparate locations in WA were genetically and phenotypically homogeneous. Furthermore, isolates of MVEV from WA and northern Queensland were almost identical, confirming results from earlier studies. Recent isolates of MVEV from Western Province in PNG were more similar to Australian isolates of MVEV than to isolates from PNG in 1956 and 1966, providing further evidence for the movement of flaviviruses between PNG and Australia. Additional representatives of a unique variant of MVEV (OR156) from Kununurra in the northeast Kimberley region of WA were also detected. This suggests that the OR156 lineage is still intermittently active but may be restricted to a small geographic area in northern WA, possibly due to altered biological characteristics.
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Antibody-dependent enhancement of Murray Valley Encephalitis virus virulence in mice.
Journal of General Virology, 2003Co-Authors: Margie Wallace, Annette K. Broom, Roy A. Hall, John S. Mackenzie, David D. Smith, Geoffrey Shellam, Peter C. McminnAbstract:Enhancement of flavivirus infection in vitro in the presence of subneutralizing concentrations of homologous or heterologous antiserum has been well described. However, the importance of this phenomenon in the enhancement of flavivirus infection in vivo has not been established. In order to study antibody-mediated enhancement of flavivirus infection in vivo, we investigated the effect of passive immunization of mice with Japanese Encephalitis virus (JE) antiserum on the outcome of infection with Murray Valley Encephalitis virus (MVE). We show that prior treatment of mice with subneutralizing concentrations of heterologous JE antiserum resulted in an increase in viraemia titres and in mortality following challenge with wild-type MVE. Our findings support the hypothesis that subneutralizing concentrations of antibody may enhance flavivirus infection and virulence in vivo. These findings are of potential importance for the design of JE vaccination programs in geographic areas in which MVE co-circulates. Should subneutralizing concentrations of antibody remain in the population following JE vaccination, it is possible that enhanced disease may be observed during MVE epidemics.
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Investigation of the southern limits of Murray Valley Encephalitis activity in Western Australia during the 2000 wet season.
Vector borne and zoonotic diseases (Larchmont N.Y.), 2002Co-Authors: Annette K. Broom, Michael D. A. Lindsay, Susan A. Harrington, D.w. SmithAbstract:Western Australia experienced its worst-ever outbreak of the mosquito-borne Murray Valley Encephalitis (MVE) virus during the 2000 wet season. Highest-on-record rainfall throughout much of the stat...
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Murray Valley Encephalitis virus surveillance and control initiatives in Australia
Communicable diseases intelligence, 2001Co-Authors: Jenean Spencer, Annette K. Broom, Michael D. A. Lindsay, Stephen L. Doggett, J. Azoulas, Tim Buick, Peter Daniels, George Hapgood, Peter J. Jarrett, Glenis LloydAbstract:Mechanisms for monitoring Murray Valley Encephalitis (MVE) virus activity include surveillance of human cases, surveillance for activity in sentinel animals, monitoring of mosquito vectors and monitoring of weather conditions. The monitoring of human cases is only one possible trigger for public health action and the additional surveillance systems are used in concert to signal the risk of human disease, often before the appearance of human cases. Mosquito vector surveillance includes mosquito trapping for speciation and enumeration of mosquitoes to monitor population sizes and relative composition. Virus isolation from mosquitoes can also be undertaken. Monitoring of weather conditions and vector surveillance determines whether there is a potential for MVE activity to occur. Virus isolation from trapped mosquitoes is necessary to define whether MVE is actually present, but is difficult to deliver in a timely fashion in some jurisdictions. Monitoring of sentinel animals indicates whether MVE transmission to vertebrates is actually occurring. Meteorological surveillance can assist in the prediction of potential MVE virus activity by signalling conditions that have been associated with outbreaks of Murray Valley Encephalitis in humans in the past. Predictive models of MVE virus activity for southeastern Australia have been developed, but due to the infrequency of outbreaks, are yet to be demonstrated as useful for the forecasting of major outbreaks. Surveillance mechanisms vary across the jurisdictions. Surveillance of human disease occurs in all States and Territories by reporting of cases to health authorities. Sentinel flocks of chickens are maintained in 4 jurisdictions (Western Australia, the Northern Territory, Victoria and New South Wales) with collaborations between Western Australia and the Northern Territory. Mosquito monitoring complements the surveillance of sentinel animals in these jurisdictions. In addition, other mosquito monitoring programs exist in other States (including South Australia and Queensland). Public health control measures may include advice to the general public and mosquito management programs to reduce the numbers of both mosquito larvae and adult vectors. Strategic plans for public health action in the event of MVE virus activity are currently developed or being developed in New South Wales, the Northern Territory, South Australia, Western Australia and Victoria. A southern tri-State agreement exists between health departments of New South Wales, Victoria and South Australia and the Commonwealth Department of Health and Aged Care. All partners have agreed to cooperate and provide assistance in predicting and combatting outbreaks of mosquito-borne disease in southeastern Australia. The newly formed National Arbovirus Advisory Committee is a working party providing advice to the Communicable Diseases Network Australia on arbovirus surveillance and control. Recommendations for further enhancement of national surveillance for Murray Valley Encephalitis are described. (author abstract)
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Murray Valley Encephalitis virus surveillance and control initiatives in Australia. National Arbovirus Advisory Committee of the Communicable Diseases Network Australia.
Communicable diseases intelligence quarterly report, 2001Co-Authors: Jenean Spencer, Annette K. Broom, Stephen L. Doggett, J. Azoulas, Tim Buick, Bart J. Currie, Peter Daniels, George Hapgood, LindsayAbstract:Mechanisms for monitoring Murray Valley Encephalitis (MVE) virus activity include surveillance of human cases, surveillance for activity in sentinel animals, monitoring of mosquito vectors and monitoring of weather conditions. The monitoring of human cases is only one possible trigger for public health action and the additional surveillance systems are used in concert to signal the risk of human disease, often before the appearance of human cases. Mosquito vector surveillance includes mosquito trapping for speciation and enumeration of mosquitoes to monitor population sizes and relative composition. Virus isolation from mosquitoes can also be undertaken. Monitoring of weather conditions and vector surveillance determines whether there is a potential for MVE activity to occur. Virus isolation from trapped mosquitoes is necessary to define whether MVE is actually present, but is difficult to deliver in a timely fashion in some jurisdictions. Monitoring of sentinel animals indicates whether MVE transmission to vertebrates is actually occurring. Meteorological surveillance can assist in the prediction of potential MVE virus activity by signalling conditions that have been associated with outbreaks of Murray Valley Encephalitis in humans in the past. Predictive models of MVE virus activity for south-eastern Australia have been developed, but due to the infrequency of outbreaks, are yet to be demonstrated as useful for the forecasting of major outbreaks. Surveillance mechanisms vary across the jurisdictions. Surveillance of human disease occurs in all States and Territories by reporting of cases to health authorities. Sentinel flocks of chickens are maintained in 4 jurisdictions (Western Australia, the Northern Territory, Victoria and New South Wales) with collaborations between Western Australia and the Northern Territory. Mosquito monitoring complements the surveillance of sentinel animals in these jurisdictions. In addition, other mosquito monitoring programs exist in other States (including South Australia and Queensland). Public health control measures may include advice to the general public and mosquito management programs to reduce the numbers of both mosquito larvae and adult vectors. Strategic plans for public health action in the event of MVE virus activity are currently developed or being developed in New South Wales, the Northern Territory, South Australia, Western Australia and Victoria. A southern tri-State agreement exists between health departments of New South Wales, Victoria and South Australia and the Commonwealth Department of Health and Aged Care. All partners have agreed to co-operate and provide assistance in predicting and combatting outbreaks of mosquito-borne disease in south-eastern Australia. The newly formed National Arbovirus Advisory Committee is a working party providing advice to the Communicable Diseases Network Australia on arbovirus surveillance and control. Recommendations for further enhancement of national surveillance for Murray Valley Encephalitis are described.
John S. Mackenzie - One of the best experts on this subject based on the ideXlab platform.
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RESEARCH ARTICLE The Molecular Epidemiology and Evolution of Murray Valley Encephalitis Virus: Recent Emergence of Distinct Sub-lineages of the Dominant Genotype 1
2016Co-Authors: David T Williams, Stephen L. Doggett, Cheryl A. Johansen, Sinéad M. Diviney¤a, Peter A. Durr, Hooi Chua, Alyssa Pyke, John S. MackenzieAbstract:Background Recent increased activity of the mosquito-borne Murray Valley Encephalitis virus (MVEV) in Australia has renewed concerns regarding its potential to spread and cause disease. Methodology/Principal Findings To better understand the genetic relationships between earlier and more recent circulating strains, patterns of virus movement, as well as the molecular basis of MVEV evolution, com-plete pre-membrane (prM) and Envelope (Env) genes were sequenced from sixty-six MVEV strains from different regions of the Australasian region, isolated over a sixty year period (1951–2011). Phylogenetic analyses indicated that, of the four recognized geno-types, only G1 and G2 are contemporary. G1 viruses were dominant over the sampling period and found across the known geographic range of MVEV. Two distinct sub-lineages of G1 were observed (1A and 1B). Although G1B strains have been isolated from acros
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Complete Genome Sequences of the Prototype Isolates of Genotypes 2, 3, and 4 of Murray Valley Encephalitis Virus
Genome announcements, 2014Co-Authors: David T Williams, Sinead M. Diviney, Karli J. Corscadden, B. Chua, John S. MackenzieAbstract:ABSTRACT Murray Valley Encephalitis virus (MVEV) (Flaviviridae family, Flavivirus genus), a mosquito-borne pathogen of humans and horses, is endemic to the Australasian region. We report here the complete genomes of the prototype strains of MVEV genotypes 2, 3, and 4.
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Murray Valley Encephalitis: a review of clinical features, diagnosis and treatment
The Medical journal of Australia, 2012Co-Authors: James Knox, John S. Mackenzie, Bart J. Currie, Raquel U Cowan, Joseph Doyle, Matthew K Ligtermoet, John S. Archer, James Burrow, Steven Y. C. Tong, D.w. SmithAbstract:Murray Valley Encephalitis virus (MVEV) is a mosquito-borne virus that is found across Australia, Papua New Guinea and Irian Jaya. MVEV is endemic to northern Australia and causes occasional outbreaks across south-eastern Australia. 2011 saw a dramatic increase in MVEV activity in endemic regions and the re-emergence of MVEV in south-eastern Australia. This followed significant regional flooding and increased numbers of the main mosquito vector, Culex annulirostris, and was evident from the widespread seroconversion of sentinel chickens, fatalities among horses and several cases in humans, resulting in at least three deaths. The last major outbreak in Australia was in 1974, during which 58 cases were identified and the mortality rate was about 20%. With the potential for a further outbreak of MVEV in the 2011-2012 summer and following autumn, we highlight the importance of this disease, its clinical characteristics and radiological and laboratory features. We present a suspected but unproven case of MVEV infection to illustrate some of the challenges in clinical management. It remains difficult to establish an early diagnosis of MVEV infection, and there is a lack of proven therapeutic options.
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Widespread transmission of distinct genetic lineages of Murray Valley Encephalitis virus in Australia, 2008-2009
2011Co-Authors: David T Williams, Sinead M. Diviney, Aziz-ur-rahman Niazi, Belinda L. Herring, Cheryl A. Johansen, John S. MackenzieAbstract:Murray Valley Encephalitis virus (MVEV) is the most important cause of arboviral neurological disease in humans in Australia. Increased activity of MVEV was observed in Australia in 2008 and 2009, leading to fatal human and equine cases, and renewed concerns regarding its potential to spread and cause disease. Four genotypes (G1-G4) of MVEV are recognised: G1 and G2 contain strains from the Australian mainland (and recent strains from Papua New Guinea), while single PNG isolates comprise G3 and G4. Complete prM-Env genes were sequenced from over 50 MVEV strains from different regions of Australia and PNG, and from different times, in order to establish genetic relationships between recent circulating strains with earlier isolates. Phylogenetic analyses showed that G1 was the dominant circulating genotype sampled over a 60 year period. Two distinct sub-lineages of G1 were observed: G1A comprised the prototype strain, recent PNG isolates as well as 2008 and 2009 Western Australian strains; G1B included early Western Australian viruses (isolated from 1972) and including 2009 (but not 2008) strains and all 2008 isolates from eastern Australia.
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An update on the molecular epidemiology of Murray Valley Encephalitis virus
2009Co-Authors: Sinead M. Diviney, John S. Mackenzie, David T Williams, Belinda L. Herring, Cheryl A. Johansen, Jane OakeyAbstract:Murray Valley Encephalitis virus (MVEV) is an encephalitogenic mosquito-borne flavivirus endemic to Australia and Papua New Guinea (PNG). The virus was first isolated from human samples in 1951 during an epidemic in the Murray Valley, Australia. Culex annulirostris is the main vector mosquito of MVEV, while various species of waterbirds are considered the major vertebrate hosts. Humans are generally thought to be dead-end hosts. Epidemics are thought to occur due to either infected birds or mosquitoes migrating from endemic areas to non-endemic areas. The increased activity of this virus in Australia in 2008 has renewed concerns regarding its potential to spread and cause disease. Four genotypes (GI-GIV) of MVEV have been previously recognized: GI and GII contain strains from the Australian mainland (with the exception of two PNG isolates from 1998), while single earlier PNG isolates comprise each of GIII and GIV. Phylogenetic analyses were performed on complete preM-Env gene sequences from 41 MVEV strains from different regions around Australia and PNG, isolated at different times. These included 2008 strains from a fatal human case in the Kimberley region of Western Australia, a fatal equine case from Monto, Queensland, and nine mosquito isolates from Leeton and Griffiths in NSW. All 2008 strains belonged to GI. The human strain showed highest levels of nt identity with the prototype strain MVEV 1-51 (96.5%). The horse isolate and mosquito isolates showed high levels of nt identity with each other (>98.3%) and with a 2002 strain from Burketown, Qld (>98.9%). The lower level of identity between the WA human strain and the Eastern Australian isolates (93.494.7%) suggests they have distinct origins. While the human strain most likely originated in the Kimberley region, where MVEV is enzootic, questions remain regarding the origin of the 2008 eastern Australian viruses. These viruses may have originated from cryptic foci in NSW or Queensland. Alternatively, they may have been re-introduced into these areas by migratory viraemic waterbirds from northern Australia. Personal Profile Sinead Diviney is a Curtin Research Fellow at the AB-CRC group located at Curtin University of Technology, Perth, Western Australia. Her research interests are characterization of viral entry, replication and evolution of emerging viruses.
Jeffrey Hill - One of the best experts on this subject based on the ideXlab platform.
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substrate based peptidomimetic inhibitors of the Murray Valley Encephalitis virus ns2b ns3 serine protease a p1 p4 sar study
European Journal of Medicinal Chemistry, 2013Co-Authors: Melgious Jin Yan Ang, Joma Joy, Jeffrey Hill, Gerald Han Jie Yong, Anders Poulsen, Siew Wen Then, Cheng San Brian ChiaAbstract:Abstract Murray Valley Encephalitis is an infectious disease spread by a mosquito-borne virus endemic in Papua New Guinea and northern Australia. In the past decade, it has spread to various regions of Australia and there is currently no therapeutic treatment against this disease. An attractive drug target is the viral serine protease NS2B/NS3, a critical enzyme involved in viral replication. Herein, we report the inhibitory activities of 37 C-terminal agmatine peptidomimetic inhibitors which led to the design of a novel structurally-constrained competitive inhibitor 38 possessing a K i of 2.5 ± 0.5 μM. We believe our data provides crucial insights into the viral protease active site specificity which could be used to facilitate drug design against Murray Valley Encephalitis viral infections.
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Substrate-based peptidomimetic inhibitors of the Murray Valley Encephalitis virus NS2B/NS3 serine protease: a P1-P4 SAR study.
European journal of medicinal chemistry, 2013Co-Authors: Melgious Jin Yan Ang, Joma Joy, Jeffrey Hill, Gerald Han Jie Yong, Anders Poulsen, Siew Wen Then, Cheng San Brian ChiaAbstract:Abstract Murray Valley Encephalitis is an infectious disease spread by a mosquito-borne virus endemic in Papua New Guinea and northern Australia. In the past decade, it has spread to various regions of Australia and there is currently no therapeutic treatment against this disease. An attractive drug target is the viral serine protease NS2B/NS3, a critical enzyme involved in viral replication. Herein, we report the inhibitory activities of 37 C-terminal agmatine peptidomimetic inhibitors which led to the design of a novel structurally-constrained competitive inhibitor 38 possessing a K i of 2.5 ± 0.5 μM. We believe our data provides crucial insights into the viral protease active site specificity which could be used to facilitate drug design against Murray Valley Encephalitis viral infections.
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solid phase synthesis and screening of a library of c terminal arginine peptide aldehydes against Murray Valley Encephalitis virus protease
Journal of Peptide Science, 2012Co-Authors: Nicholas J. Ede, Joma Joy, Jeffrey Hill, Anne-marie Ede, Merran L. KoppensAbstract:Murray Valley Encephalitis virus is a member of the flavivirus group, a large family of single-stranded RNA viruses, which cause serious disease in all regions of the world. Unfortunately, no suitable antivirals are available, and there are commercial vaccines for only three flaviviruses. The solid-phase synthesis of a library of 400 C-terminal arginine peptide aldehydes and their screening against Murray Valley Encephalitis virus protease are demonstrated. The library was utilised to elucidate several tripeptide sequences that can be used as inhibitors in further SAR studies. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.
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Solid‐phase synthesis and screening of a library of C‐terminal arginine peptide aldehydes against Murray Valley Encephalitis virus protease
Journal of peptide science : an official publication of the European Peptide Society, 2012Co-Authors: Nicholas J. Ede, Joma Joy, Jeffrey Hill, Anne-marie Ede, Merran L. KoppensAbstract:Murray Valley Encephalitis virus is a member of the flavivirus group, a large family of single-stranded RNA viruses, which cause serious disease in all regions of the world. Unfortunately, no suitable antivirals are available, and there are commercial vaccines for only three flaviviruses. The solid-phase synthesis of a library of 400 C-terminal arginine peptide aldehydes and their screening against Murray Valley Encephalitis virus protease are demonstrated. The library was utilised to elucidate several tripeptide sequences that can be used as inhibitors in further SAR studies. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.
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Biochemical characterisation of Murray Valley Encephalitis virus proteinase.
FEBS letters, 2010Co-Authors: Joma Joy, Ng Fui Mee, Wee Liang Kuan, Kwek Zekui Perlyn, Then Siew Wen, Jeffrey HillAbstract:Abstract Murray Valley Encephalitis virus (MVEV) is a member of the flavivirus group, a large family of single stranded RNA viruses, which cause serious disease in all regions of the world. Its genome encodes a large polyprotein which is processed by both host proteinases and a virally encoded serine proteinase, non-structural protein 3 (NS3). NS3, an essential viral enzyme, requires another virally encoded protein cofactor, NS2B, for proteolytic activity. The cloning, expression and biochemical characterisation of a stable MVEV NS2B–NS3 fusion protein is described.
Joma Joy - One of the best experts on this subject based on the ideXlab platform.
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substrate based peptidomimetic inhibitors of the Murray Valley Encephalitis virus ns2b ns3 serine protease a p1 p4 sar study
European Journal of Medicinal Chemistry, 2013Co-Authors: Melgious Jin Yan Ang, Joma Joy, Jeffrey Hill, Gerald Han Jie Yong, Anders Poulsen, Siew Wen Then, Cheng San Brian ChiaAbstract:Abstract Murray Valley Encephalitis is an infectious disease spread by a mosquito-borne virus endemic in Papua New Guinea and northern Australia. In the past decade, it has spread to various regions of Australia and there is currently no therapeutic treatment against this disease. An attractive drug target is the viral serine protease NS2B/NS3, a critical enzyme involved in viral replication. Herein, we report the inhibitory activities of 37 C-terminal agmatine peptidomimetic inhibitors which led to the design of a novel structurally-constrained competitive inhibitor 38 possessing a K i of 2.5 ± 0.5 μM. We believe our data provides crucial insights into the viral protease active site specificity which could be used to facilitate drug design against Murray Valley Encephalitis viral infections.
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Substrate-based peptidomimetic inhibitors of the Murray Valley Encephalitis virus NS2B/NS3 serine protease: a P1-P4 SAR study.
European journal of medicinal chemistry, 2013Co-Authors: Melgious Jin Yan Ang, Joma Joy, Jeffrey Hill, Gerald Han Jie Yong, Anders Poulsen, Siew Wen Then, Cheng San Brian ChiaAbstract:Abstract Murray Valley Encephalitis is an infectious disease spread by a mosquito-borne virus endemic in Papua New Guinea and northern Australia. In the past decade, it has spread to various regions of Australia and there is currently no therapeutic treatment against this disease. An attractive drug target is the viral serine protease NS2B/NS3, a critical enzyme involved in viral replication. Herein, we report the inhibitory activities of 37 C-terminal agmatine peptidomimetic inhibitors which led to the design of a novel structurally-constrained competitive inhibitor 38 possessing a K i of 2.5 ± 0.5 μM. We believe our data provides crucial insights into the viral protease active site specificity which could be used to facilitate drug design against Murray Valley Encephalitis viral infections.
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solid phase synthesis and screening of a library of c terminal arginine peptide aldehydes against Murray Valley Encephalitis virus protease
Journal of Peptide Science, 2012Co-Authors: Nicholas J. Ede, Joma Joy, Jeffrey Hill, Anne-marie Ede, Merran L. KoppensAbstract:Murray Valley Encephalitis virus is a member of the flavivirus group, a large family of single-stranded RNA viruses, which cause serious disease in all regions of the world. Unfortunately, no suitable antivirals are available, and there are commercial vaccines for only three flaviviruses. The solid-phase synthesis of a library of 400 C-terminal arginine peptide aldehydes and their screening against Murray Valley Encephalitis virus protease are demonstrated. The library was utilised to elucidate several tripeptide sequences that can be used as inhibitors in further SAR studies. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.
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Solid‐phase synthesis and screening of a library of C‐terminal arginine peptide aldehydes against Murray Valley Encephalitis virus protease
Journal of peptide science : an official publication of the European Peptide Society, 2012Co-Authors: Nicholas J. Ede, Joma Joy, Jeffrey Hill, Anne-marie Ede, Merran L. KoppensAbstract:Murray Valley Encephalitis virus is a member of the flavivirus group, a large family of single-stranded RNA viruses, which cause serious disease in all regions of the world. Unfortunately, no suitable antivirals are available, and there are commercial vaccines for only three flaviviruses. The solid-phase synthesis of a library of 400 C-terminal arginine peptide aldehydes and their screening against Murray Valley Encephalitis virus protease are demonstrated. The library was utilised to elucidate several tripeptide sequences that can be used as inhibitors in further SAR studies. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.
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Biochemical characterisation of Murray Valley Encephalitis virus proteinase.
FEBS letters, 2010Co-Authors: Joma Joy, Ng Fui Mee, Wee Liang Kuan, Kwek Zekui Perlyn, Then Siew Wen, Jeffrey HillAbstract:Abstract Murray Valley Encephalitis virus (MVEV) is a member of the flavivirus group, a large family of single stranded RNA viruses, which cause serious disease in all regions of the world. Its genome encodes a large polyprotein which is processed by both host proteinases and a virally encoded serine proteinase, non-structural protein 3 (NS3). NS3, an essential viral enzyme, requires another virally encoded protein cofactor, NS2B, for proteolytic activity. The cloning, expression and biochemical characterisation of a stable MVEV NS2B–NS3 fusion protein is described.
