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Laura D Kramer - One of the best experts on this subject based on the ideXlab platform.
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the prevalence of zoonotic tick borne pathogens in ixodes scapularis collected in the hudson valley new york state
Vector-borne and Zoonotic Diseases, 2014Co-Authors: Matthew T Aliota, Alan P. Dupuis, Michael P Wilczek, Ryan J Peters, Richard S Ostfeld, Laura D KramerAbstract:Ixodes scapularis, the blacklegged tick, is capable of transmitting the pathogens that cause Lyme disease (Borrelia burgdorferi), babesiosis (Babesia microti), anaplasmosis (Anaplasma phagocytophilum), and to a lesser extent Powassan Encephalitis (deer tick virus [DTV]). These pathogens represent significant public health problems, but little is known about the occurrence and co-infection prevalence of these pathogens in I. scapularis. Here, we used standard PCR and pathogen-specific primers to estimate the prevalence of infection of A. phagocytophilium, B. burgdorferi, B. microti, and Ehrlichia chaffeensis in questing nymph and adult I. scapularis collected from sites in Putnam and Dutchess counties in southern New York in 2011. To detect DTV infection, cell cultures were observed for the presence of cytopathic effects and positive results were confirmed via real time RT-PCR. In 466 individually sampled adult ticks, B. burgdorferi had the highest prevalence of infection (55%) followed by A. phagocytophilum (18.2%), DTV (3.4%), B. microti (3.2%), and E. chaffeensis (1.5%). Infection with two pathogens occurred in 13.3% of ticks, and 10 ticks were infected with three combinations of three pathogens. These results provide an estimate of the rate of co-infection, which then can help inform the epidemiological risk of contracting multiple zoonotic tick-borne pathogens within the Hudson Valley region of New York State.
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potential role of deer tick virus in Powassan Encephalitis cases in lyme disease endemic areas of new york usa
Emerging Infectious Diseases, 2013Co-Authors: Marc El Y Khoury, Laura D Kramer, Alan P. Dupuis, Jose F. Camargo, Jennifer L. White, Bryon Backenson, Kay L. Escuyer, Kirsten St. George, Debarati Chatterjee, Melissa A PrusinskiAbstract:Powassan virus is a positive-sense RNA virus that belongs to the tick-borne Encephalitis group of flaviviruses (1). The first recognized case of Powassan Encephalitis in North America was from Canada in 1958 (2); the first case in Russia was from the Primorsky Krai region in 1972 (3). Powassan virus comprises 2 closely related lineages: the Powassan virus prototype (POWV) lineage and the deer tick virus (DTV) lineage. POWV and DTV, which share 84% nucleotide sequence identity and 94% amino acid sequence identity (4), have a common ancestral origin, from which they diverged around 485 years ago (5). Each lineage has separate tick vectors and reservoir hosts in North America (5). POWV is maintained in an enzootic cycle between Ixodes cookei as the tick vector and the groundhog (Marmota momax) and striped skunk (Mephitis mephitis) as the principal reservoir hosts (6). DTV is believed to be maintained between I. scapularis ticks and the white-footed mouse (Peromyscus leucopus) (7,8). DTV can be accurately differentiated from POWV only by genetic sequence analysis. Four cases of proven DTV Encephalitis have been reported: 1 from Ontario, Canada (4,9); 2 from New York (10,11); and 1 from Minnesota (12). For clarity, in this article, we will use the term POWV/DTV to designate infection with Powassan virus of undetermined lineage. We present a detailed description of the clinical signs and symptoms, laboratory diagnosis, and outcome of the 14 cases of POWV/DTV Encephalitis diagnosed during 2004–2012 in New York. We also provide a review of the literature for epidemiologic evidence suggesting that many of these cases were caused by DTV rather than POWV.
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Potential Role of Deer Tick Virus in Powassan Encephalitis Cases in Lyme Disease–endemic Areas of New York, USA
Emerging infectious diseases, 2013Co-Authors: Marc Y. El Khoury, Laura D Kramer, Alan P. Dupuis, Jose F. Camargo, Jennifer L. White, Bryon Backenson, Kay L. Escuyer, Kirsten St. George, Debarati Chatterjee, Melissa A PrusinskiAbstract:Powassan virus is a positive-sense RNA virus that belongs to the tick-borne Encephalitis group of flaviviruses (1). The first recognized case of Powassan Encephalitis in North America was from Canada in 1958 (2); the first case in Russia was from the Primorsky Krai region in 1972 (3). Powassan virus comprises 2 closely related lineages: the Powassan virus prototype (POWV) lineage and the deer tick virus (DTV) lineage. POWV and DTV, which share 84% nucleotide sequence identity and 94% amino acid sequence identity (4), have a common ancestral origin, from which they diverged around 485 years ago (5). Each lineage has separate tick vectors and reservoir hosts in North America (5). POWV is maintained in an enzootic cycle between Ixodes cookei as the tick vector and the groundhog (Marmota momax) and striped skunk (Mephitis mephitis) as the principal reservoir hosts (6). DTV is believed to be maintained between I. scapularis ticks and the white-footed mouse (Peromyscus leucopus) (7,8). DTV can be accurately differentiated from POWV only by genetic sequence analysis. Four cases of proven DTV Encephalitis have been reported: 1 from Ontario, Canada (4,9); 2 from New York (10,11); and 1 from Minnesota (12). For clarity, in this article, we will use the term POWV/DTV to designate infection with Powassan virus of undetermined lineage. We present a detailed description of the clinical signs and symptoms, laboratory diagnosis, and outcome of the 14 cases of POWV/DTV Encephalitis diagnosed during 2004–2012 in New York. We also provide a review of the literature for epidemiologic evidence suggesting that many of these cases were caused by DTV rather than POWV.
Melissa A Prusinski - One of the best experts on this subject based on the ideXlab platform.
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potential role of deer tick virus in Powassan Encephalitis cases in lyme disease endemic areas of new york usa
Emerging Infectious Diseases, 2013Co-Authors: Marc El Y Khoury, Laura D Kramer, Alan P. Dupuis, Jose F. Camargo, Jennifer L. White, Bryon Backenson, Kay L. Escuyer, Kirsten St. George, Debarati Chatterjee, Melissa A PrusinskiAbstract:Powassan virus is a positive-sense RNA virus that belongs to the tick-borne Encephalitis group of flaviviruses (1). The first recognized case of Powassan Encephalitis in North America was from Canada in 1958 (2); the first case in Russia was from the Primorsky Krai region in 1972 (3). Powassan virus comprises 2 closely related lineages: the Powassan virus prototype (POWV) lineage and the deer tick virus (DTV) lineage. POWV and DTV, which share 84% nucleotide sequence identity and 94% amino acid sequence identity (4), have a common ancestral origin, from which they diverged around 485 years ago (5). Each lineage has separate tick vectors and reservoir hosts in North America (5). POWV is maintained in an enzootic cycle between Ixodes cookei as the tick vector and the groundhog (Marmota momax) and striped skunk (Mephitis mephitis) as the principal reservoir hosts (6). DTV is believed to be maintained between I. scapularis ticks and the white-footed mouse (Peromyscus leucopus) (7,8). DTV can be accurately differentiated from POWV only by genetic sequence analysis. Four cases of proven DTV Encephalitis have been reported: 1 from Ontario, Canada (4,9); 2 from New York (10,11); and 1 from Minnesota (12). For clarity, in this article, we will use the term POWV/DTV to designate infection with Powassan virus of undetermined lineage. We present a detailed description of the clinical signs and symptoms, laboratory diagnosis, and outcome of the 14 cases of POWV/DTV Encephalitis diagnosed during 2004–2012 in New York. We also provide a review of the literature for epidemiologic evidence suggesting that many of these cases were caused by DTV rather than POWV.
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Potential Role of Deer Tick Virus in Powassan Encephalitis Cases in Lyme Disease–endemic Areas of New York, USA
Emerging infectious diseases, 2013Co-Authors: Marc Y. El Khoury, Laura D Kramer, Alan P. Dupuis, Jose F. Camargo, Jennifer L. White, Bryon Backenson, Kay L. Escuyer, Kirsten St. George, Debarati Chatterjee, Melissa A PrusinskiAbstract:Powassan virus is a positive-sense RNA virus that belongs to the tick-borne Encephalitis group of flaviviruses (1). The first recognized case of Powassan Encephalitis in North America was from Canada in 1958 (2); the first case in Russia was from the Primorsky Krai region in 1972 (3). Powassan virus comprises 2 closely related lineages: the Powassan virus prototype (POWV) lineage and the deer tick virus (DTV) lineage. POWV and DTV, which share 84% nucleotide sequence identity and 94% amino acid sequence identity (4), have a common ancestral origin, from which they diverged around 485 years ago (5). Each lineage has separate tick vectors and reservoir hosts in North America (5). POWV is maintained in an enzootic cycle between Ixodes cookei as the tick vector and the groundhog (Marmota momax) and striped skunk (Mephitis mephitis) as the principal reservoir hosts (6). DTV is believed to be maintained between I. scapularis ticks and the white-footed mouse (Peromyscus leucopus) (7,8). DTV can be accurately differentiated from POWV only by genetic sequence analysis. Four cases of proven DTV Encephalitis have been reported: 1 from Ontario, Canada (4,9); 2 from New York (10,11); and 1 from Minnesota (12). For clarity, in this article, we will use the term POWV/DTV to designate infection with Powassan virus of undetermined lineage. We present a detailed description of the clinical signs and symptoms, laboratory diagnosis, and outcome of the 14 cases of POWV/DTV Encephalitis diagnosed during 2004–2012 in New York. We also provide a review of the literature for epidemiologic evidence suggesting that many of these cases were caused by DTV rather than POWV.
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Potential Role of Deer Tick Virus in Powassan Encephalitis Cases in Lyme Disease–endemic Areas of New York, USA
Centers for Disease Control and Prevention, 2013Co-Authors: Marc El Y Khoury, Alan P. Dupuis, Jose F. Camargo, Jennifer L. White, Bryon Backenson, Kay L. Escuyer, Kirsten St. George, Debarati Chatterjee, Laura Kramer, Melissa A PrusinskiAbstract:Powassan virus, a member of the tick-borne Encephalitis group of flaviviruses, encompasses 2 lineages with separate enzootic cycles. The prototype lineage of Powassan virus (POWV) is principally maintained between Ixodes cookei ticks and the groundhog (Marmota momax) or striped skunk (Mephitis mephitis), whereas the deer tick virus (DTV) lineage is believed to be maintained between Ixodes scapularis ticks and the white-footed mouse (Peromyscus leucopus). We report 14 cases of Powassan Encephalitis from New York during 2004–2012. Ten (72%) of the patients were residents of the Lower Hudson Valley, a Lyme disease–endemic area in which I. scapularis ticks account for most human tick bites. This finding suggests that many of these cases were caused by DTV rather than POWV. In 2 patients, DTV infection was confirmed by genetic sequencing. As molecular testing becomes increasingly available, more cases of Powassan Encephalitis may be determined to be attributable to the DTV lineage
Alan P. Dupuis - One of the best experts on this subject based on the ideXlab platform.
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Potential Role of Deer Tick Virus in Powassan Encephalitis Cases in
2016Co-Authors: Lyme Disease–endemic Areas, Alan P. Dupuis, Jose F. Camargo, Jennifer L. White, Bryon Backenson, Kay L. Escuyer, Kirsten St. George, Marc El Y Khoury, Laura Kramer, Debarati ChatterjeeAbstract:Powassan virus, a member of the tick-borne enceph-alitis group of flaviviruses, encompasses 2 lineages with separate enzootic cycles. The prototype lineage of Powas-san virus (POWV) is principally maintained between Ixo-des cookei ticks and the groundhog (Marmota momax) o
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the prevalence of zoonotic tick borne pathogens in ixodes scapularis collected in the hudson valley new york state
Vector-borne and Zoonotic Diseases, 2014Co-Authors: Matthew T Aliota, Alan P. Dupuis, Michael P Wilczek, Ryan J Peters, Richard S Ostfeld, Laura D KramerAbstract:Ixodes scapularis, the blacklegged tick, is capable of transmitting the pathogens that cause Lyme disease (Borrelia burgdorferi), babesiosis (Babesia microti), anaplasmosis (Anaplasma phagocytophilum), and to a lesser extent Powassan Encephalitis (deer tick virus [DTV]). These pathogens represent significant public health problems, but little is known about the occurrence and co-infection prevalence of these pathogens in I. scapularis. Here, we used standard PCR and pathogen-specific primers to estimate the prevalence of infection of A. phagocytophilium, B. burgdorferi, B. microti, and Ehrlichia chaffeensis in questing nymph and adult I. scapularis collected from sites in Putnam and Dutchess counties in southern New York in 2011. To detect DTV infection, cell cultures were observed for the presence of cytopathic effects and positive results were confirmed via real time RT-PCR. In 466 individually sampled adult ticks, B. burgdorferi had the highest prevalence of infection (55%) followed by A. phagocytophilum (18.2%), DTV (3.4%), B. microti (3.2%), and E. chaffeensis (1.5%). Infection with two pathogens occurred in 13.3% of ticks, and 10 ticks were infected with three combinations of three pathogens. These results provide an estimate of the rate of co-infection, which then can help inform the epidemiological risk of contracting multiple zoonotic tick-borne pathogens within the Hudson Valley region of New York State.
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potential role of deer tick virus in Powassan Encephalitis cases in lyme disease endemic areas of new york usa
Emerging Infectious Diseases, 2013Co-Authors: Marc El Y Khoury, Laura D Kramer, Alan P. Dupuis, Jose F. Camargo, Jennifer L. White, Bryon Backenson, Kay L. Escuyer, Kirsten St. George, Debarati Chatterjee, Melissa A PrusinskiAbstract:Powassan virus is a positive-sense RNA virus that belongs to the tick-borne Encephalitis group of flaviviruses (1). The first recognized case of Powassan Encephalitis in North America was from Canada in 1958 (2); the first case in Russia was from the Primorsky Krai region in 1972 (3). Powassan virus comprises 2 closely related lineages: the Powassan virus prototype (POWV) lineage and the deer tick virus (DTV) lineage. POWV and DTV, which share 84% nucleotide sequence identity and 94% amino acid sequence identity (4), have a common ancestral origin, from which they diverged around 485 years ago (5). Each lineage has separate tick vectors and reservoir hosts in North America (5). POWV is maintained in an enzootic cycle between Ixodes cookei as the tick vector and the groundhog (Marmota momax) and striped skunk (Mephitis mephitis) as the principal reservoir hosts (6). DTV is believed to be maintained between I. scapularis ticks and the white-footed mouse (Peromyscus leucopus) (7,8). DTV can be accurately differentiated from POWV only by genetic sequence analysis. Four cases of proven DTV Encephalitis have been reported: 1 from Ontario, Canada (4,9); 2 from New York (10,11); and 1 from Minnesota (12). For clarity, in this article, we will use the term POWV/DTV to designate infection with Powassan virus of undetermined lineage. We present a detailed description of the clinical signs and symptoms, laboratory diagnosis, and outcome of the 14 cases of POWV/DTV Encephalitis diagnosed during 2004–2012 in New York. We also provide a review of the literature for epidemiologic evidence suggesting that many of these cases were caused by DTV rather than POWV.
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Potential Role of Deer Tick Virus in Powassan Encephalitis Cases in Lyme Disease–endemic Areas of New York, USA
Emerging infectious diseases, 2013Co-Authors: Marc Y. El Khoury, Laura D Kramer, Alan P. Dupuis, Jose F. Camargo, Jennifer L. White, Bryon Backenson, Kay L. Escuyer, Kirsten St. George, Debarati Chatterjee, Melissa A PrusinskiAbstract:Powassan virus is a positive-sense RNA virus that belongs to the tick-borne Encephalitis group of flaviviruses (1). The first recognized case of Powassan Encephalitis in North America was from Canada in 1958 (2); the first case in Russia was from the Primorsky Krai region in 1972 (3). Powassan virus comprises 2 closely related lineages: the Powassan virus prototype (POWV) lineage and the deer tick virus (DTV) lineage. POWV and DTV, which share 84% nucleotide sequence identity and 94% amino acid sequence identity (4), have a common ancestral origin, from which they diverged around 485 years ago (5). Each lineage has separate tick vectors and reservoir hosts in North America (5). POWV is maintained in an enzootic cycle between Ixodes cookei as the tick vector and the groundhog (Marmota momax) and striped skunk (Mephitis mephitis) as the principal reservoir hosts (6). DTV is believed to be maintained between I. scapularis ticks and the white-footed mouse (Peromyscus leucopus) (7,8). DTV can be accurately differentiated from POWV only by genetic sequence analysis. Four cases of proven DTV Encephalitis have been reported: 1 from Ontario, Canada (4,9); 2 from New York (10,11); and 1 from Minnesota (12). For clarity, in this article, we will use the term POWV/DTV to designate infection with Powassan virus of undetermined lineage. We present a detailed description of the clinical signs and symptoms, laboratory diagnosis, and outcome of the 14 cases of POWV/DTV Encephalitis diagnosed during 2004–2012 in New York. We also provide a review of the literature for epidemiologic evidence suggesting that many of these cases were caused by DTV rather than POWV.
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Potential Role of Deer Tick Virus in Powassan Encephalitis Cases in Lyme Disease–endemic Areas of New York, USA
Centers for Disease Control and Prevention, 2013Co-Authors: Marc El Y Khoury, Alan P. Dupuis, Jose F. Camargo, Jennifer L. White, Bryon Backenson, Kay L. Escuyer, Kirsten St. George, Debarati Chatterjee, Laura Kramer, Melissa A PrusinskiAbstract:Powassan virus, a member of the tick-borne Encephalitis group of flaviviruses, encompasses 2 lineages with separate enzootic cycles. The prototype lineage of Powassan virus (POWV) is principally maintained between Ixodes cookei ticks and the groundhog (Marmota momax) or striped skunk (Mephitis mephitis), whereas the deer tick virus (DTV) lineage is believed to be maintained between Ixodes scapularis ticks and the white-footed mouse (Peromyscus leucopus). We report 14 cases of Powassan Encephalitis from New York during 2004–2012. Ten (72%) of the patients were residents of the Lower Hudson Valley, a Lyme disease–endemic area in which I. scapularis ticks account for most human tick bites. This finding suggests that many of these cases were caused by DTV rather than POWV. In 2 patients, DTV infection was confirmed by genetic sequencing. As molecular testing becomes increasingly available, more cases of Powassan Encephalitis may be determined to be attributable to the DTV lineage
Mats Haglund - One of the best experts on this subject based on the ideXlab platform.
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Tick-Borne Encephalopathies
CNS Drugs, 2005Co-Authors: Göran Günther, Mats HaglundAbstract:Tick-borne encephalopathies constitute a broad range of infectious diseases affecting the brain and other parts of the CNS. The causative agents are both viral and bacterial. This review focuses on the current most important tick-borne human diseases: tick-borne Encephalitis (TBE; including Powassan Encephalitis) and Lyme borreliosis. Rocky Mountain spotted fever (RMSF) and Colorado tick fever (CTF), less common tick-borne diseases associated with encephalopathy, are also discussed. TBE is the most important flaviviral infection of the CNS in Europe and Russia, with 10 000–12 000 people diagnosed annually. The lethality of TBE in Europe is 0.5% and a post-encephalitic syndrome is seen in over 40% of affected patients, often producing a pronounced impairment in quality of life. There is no specific treatment for TBE. Two vaccines are available to prevent infection. Although these have a good protection rate and good efficacy, there are few data on long-term immunity. Lyme borreliosis is the most prevalent tick-borne disease in Europe and North America, with >50 000 cases annually. Localised early disease can be treated with oral phenoxymethylpenicillin (penicillin V), doxycycline or amoxicillin. The later manifestations of meningitis, arthritis or acrodermatitis can be treated with oral doxycycline, oral amoxicillin or intravenous ceftriaxone; intravenous benzylpenicillin (penicillin G) or cefotaxime can be used as alternatives. The current use of vaccines against Lyme borreliosis in North America is under discussion, as the LYMErix™ vaccine has been withdrawn from the market because of possible adverse effects, for example, arthritis. RMSF and CTF appear only in North America. RMSF is an important rickettsial disease and is effectively treated with doxycycline. There is no treatment or preventative measure available for CTF.
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Tick-borne encephalopathies : epidemiology, diagnosis, treatment and prevention.
CNS drugs, 2005Co-Authors: Göran Günther, Mats HaglundAbstract:Tick-borne encephalopathies constitute a broad range of infectious diseases affecting the brain and other parts of the CNS. The causative agents are both viral and bacterial. This review focuses on the current most important tick-borne human diseases: tick-borne Encephalitis (TBE; including Powassan Encephalitis) and Lyme borreliosis. Rocky Mountain spotted fever (RMSF) and Colorado tick fever (CTF), less common tick-borne diseases associated with encephalopathy, are also discussed. TBE is the most important flaviviral infection of the CNS in Europe and Russia, with 10 000-12 000 people diagnosed annually. The lethality of TBE in Europe is 0.5% and a post-encephalitic syndrome is seen in over 40% of affected patients, often producing a pronounced impairment in quality of life. There is no specific treatment for TBE. Two vaccines are available to prevent infection. Although these have a good protection rate and good efficacy, there are few data on long-term immunity. Lyme borreliosis is the most prevalent tick-borne disease in Europe and North America, with >50 000 cases annually. Localised early disease can be treated with oral phenoxymethylpenicillin (penicillin V), doxycycline or amoxicillin. The later manifestations of meningitis, arthritis or acrodermatitis can be treated with oral doxycycline, oral amoxicillin or intravenous ceftriaxone; intravenous benzylpenicillin (penicillin G) or cefotaxime can be used as alternatives. The current use of vaccines against Lyme borreliosis in North America is under discussion, as the LYMErix vaccine has been withdrawn from the market because of possible adverse effects, for example, arthritis. RMSF and CTF appear only in North America. RMSF is an important rickettsial disease and is effectively treated with doxycycline. There is no treatment or preventative measure available for CTF.
Vladimir M. Pentkovski - One of the best experts on this subject based on the ideXlab platform.
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Interaction of Flaviviruses with Reproduction Inhibitors Binding in β-OG Pocket: Insights from Molecular Dynamics Simulations.
Molecular informatics, 2014Co-Authors: Evgenia V. Dueva, Dmitry I. Osolodkin, Liubov I. Kozlovskaya, Vladimir A. Palyulin, Vladimir M. Pentkovski, Nikolay S. ZefirovAbstract:Flaviviral diseases, including dengue fever, West Nile fever, yellow fever, tick-borne Encephalitis, Omsk haemorrhagic fever, and Powassan Encephalitis, threaten human health all over the world. Lack of effective antivirals targeting replication cycle of flaviviruses makes the search of such compounds a challenging task. Recently we have identified a reproduction inhibitor effective against tick-borne Encephalitis virus and Powassan virus (POWV) (ACS Med. Chem. Lett., 2013, 4, 869-874). To enable using this inhibitor as a template for 3D pharmacophore search, a biologically active conformation of this molecule should have been established. Here we performed molecular dynamics simulations of the complexes between the different enantiomers of the inhibitor and POWV envelope (E) proteins, putative targets of the inhibitor, in the different protonation states corresponding to the different stages of membrane fusion process. Several stable conformations of the inhibitor were identified, opening routes for further design of more advanced molecules.
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Computational Studies of Flaviviruses: Approaching to Novel Fusion Inhibitors
Journal of Cheminformatics, 2012Co-Authors: Dmitry I. Osolodkin, Evgenia V. Dueva, Liubov I. Kozlovskaya, Vladimir A. Palyulin, Nikolay S. Zefirov, Galina G Karganova, Vladimir M. PentkovskiAbstract:Flaviviral infections affect millions of people throughout the world, in such different territories as Europe, Australia, USA, and China. Among these infections are dengue fever, tick-borne Encephalitis, Powassan Encephalitis, West Nile fever, yellow fever, Omsk haemorrhagic fever, etc. Effective vaccines exist against only several flaviviruses. Moreover, there is no other specific therapy for flaviviral infections; consequently, new antiviral drugs are needed for the treatment of these diseases. Falviviruses are characterised by enveloped virion with E protein forming its outer surface. During the entry to the target cell E protein undergoes pH-induced conformational switch into fusogenic state that drives fusion of virion and cell membranes with consequent release of the viral genome into cytoplasm. Our studies are devoted to the modelling of flavivirus virion envelope proteins structure and molecular dynamics simulation, generally aiming in design of the fusion inhibitors. First, we studied ectodomain of TBEV E protein and revealed the possible mechanism of differences in virus binding to glycosaminoglycans [1]. Second, the analysis of point substitutions in TBEV E protein ectodomain in MD simulation study revealed the basis of their influence on the virion properties. These studies were expanded to include the stem and anchor region of this protein and describe its interactions with the viral membrane. The global aim of this study is an atom-scale simulation of viral fusion process. Another aspect of the fusion inhibitor design is analysis of the inhibitor binding site composition and structure-based virtual screening of the putative inhibitors. Such analysis has been performed for DENV, TBEV and POWV and allowed identifying molecules with high probability to inhibit the crucial step of these infections.
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POSTER PRESENTATION Computational studies of flaviviruses: approaching to novel fusion inhibitors Open Access
2011Co-Authors: Dmitry I. Osolodkin, Evgenia V. Dueva, Liubov I. Kozlovskaya, Vladimir A. Palyulin, Nikolay S. Zefirov, Galina G Karganova, Vladimir M. PentkovskiAbstract:Flaviviral infections affect millions of people throughout the world, in such different territories as Europe, Australia, USA, and China. Among these infections are dengue fever, tick-borne Encephalitis, Powassan Encephalitis, West Nile fever, yellow fever, Omsk haemorrhagic fever, etc. Effective vaccines exist against only several flaviviruses. Moreover, there is no other specific therapy for flaviviral infections; consequently, new antiviral drugs are needed for the treatment of these diseases. Falviviruses are characterised by enveloped virion with E protein forming its outer surface. During the entry to the target cell E protein undergoes pH-induced conformational switch into fusogenic state that drives fusion of virion and cell membranes with consequent release of the viral genome into cytoplasm. Our studies are devoted to the modelling of flavivirus virion envelope proteins structure and molecular dynamics simulation, generally aiming in design of the fusion inhibitors. First, we studied ectodomain of TBEV E protein and revealed the possible mechanism of differences in virus binding to glycosaminoglycans [1]. Second, the analysis of point substitutions in TBEV E protein ectodomain in MD simulation study revealed the basis of their influence on the virion properties. These studies were expanded to include the stem and anchor region of this protein and describe its interactions with the viral membrane. The global aim of this study is an atom-scale simulation of viral fusion process. Another aspect of the fusion inhibitor design is analysis of the inhibitor binding site composition and structure-based virtual screening of the putative inhibitors. Such analysis has been performed for DENV, TBEV an