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Phosphonate inhibitors of West Nile virus NS2B/NS3 protease.
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West Nile virus (WNV) is a member of the flavivirus genus belonging to the Flaviviridae family. The viral serine protease NS2B/NS3 has been considered an attractive target for the development of anti-WNV agents. Although several NS2B/NS3 protease inhibitors have been described so far, most of them
West Nile Virus NS2B/NS3 protease as an antiviral target.
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West Nile Virus (WNV) has spread rapidly during the last decade across five continents causing disease and fatalities in humans and mammals. It highlights the serious threat to both our health and the economy posed by viruses crossing species, in this case from migratory birds via mosquitoes to
Effects of detergents on the West Nile virus protease activity.
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Detergents such as Triton X-100 are often used in drug discovery research to weed out small molecule promiscuous and non-specific inhibitors which act by aggregation in solution and undesirable precipitation in aqueous assay buffers. We evaluated the effects of commonly used detergents, Triton
Arylcyanoacrylamides as inhibitors of the Dengue and West Nile virus proteases.
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The 3-aryl-2-cyanoacrylamide scaffold was designed as core pharmacophore for inhibitors of the Dengue and West Nile virus serine proteases (NS2B-NS3). A total of 86 analogs was prepared to study the structure-activity relationships in detail. Thereby, it turned out that the electron density of the
Small molecule pan-dengue and West Nile virus NS3 protease inhibitors.
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BACKGROUND
Dengue fever, dengue haemorrhagic fever, and dengue shock syndrome are caused by infections with any of the four serotypes of the dengue virus (DENV), and are an increasing global health risk. The related West Nile virus (WNV) causes significant morbidity and mortality as well, and
Proteases from dengue, West Nile and Zika viruses as drug targets.
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Proteases from flaviviruses have gained substantial interest as potential drug targets to combat infectious diseases caused by dengue, West Nile, Zika and related viruses. Despite nearly two decades of drug discovery campaigns, promising lead compounds for clinical trials have not yet been
Tripeptide inhibitors of dengue and West Nile virus NS2B-NS3 protease.
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A series of tripeptide aldehyde inhibitors were synthesized and their inhibitory effect against dengue virus type 2 (DENV2) and West Nile virus (WNV) NS3 protease was evaluated side by side with the aim to discover potent flaviviral protease inhibitors and to examine differences in specificity of
Substrate inhibition kinetic model for West Nile virus NS2B-NS3 protease.
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West Nile virus (WNV) has recently emerged in North America as a significant disease threat to humans and animals. Unfortunately, no approved antiviral drugs exist to combat WNV or other members of the genus Flavivirus in humans. The WNV NS2B-NS3 protease has been one of the primary targets for
Characterization of the West Nile virus protease substrate specificity and inhibitors.
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West Nile virus (WNV), a mosquito-borne member of Flaviviridae, is a human pathogen causing widespread disease for which there is no vaccine or chemotherapy. The two-component viral serine protease consists of a heterodimeric complex between the hydrophilic domain of the cofactor, NS2B (NS2BH) and
West Nile Virus (WNV) protease and membrane interactions revealed by NMR spectroscopy.
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West Nile Virus (WNV) protease is a two-component protease, important for the maturation of virus by cleaving the viral ploypeptide into functional proteins. WNV protease contains a Nonstructural (NS) protein 3 possessing the protease active sites and is regulated by a cofactor region containing
Structure of West Nile virus NS3 protease: ligand stabilization of the catalytic conformation.
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Over the last decade, West Nile virus has spread rapidly via mosquito transmission from infected migratory birds to humans. One potential therapeutic approach to treating infection is to inhibit the virally encoded serine protease that is essential for viral replication. Here we report the crystal
Peptide inhibitors of West Nile NS3 protease: SAR study of tetrapeptide aldehyde inhibitors.
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A series of inhibitors related to the benzoyl-norleucine-lysine-arginine-arginine (Bz-nKRR) tetrapeptide aldehyde was synthesized. When evaluated against the West Nile virus (WNV) NS3 protease, the measured IC(50) ranges from approximately 1 to 200 microM. Concurrently, a modeling study using the
New avenues for therapeutic discovery against West Nile virus.
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Introduction: West Nile virus (WNV) is a neurotropic mosquito-borne flavivirus, which is endemic in many countries, especially in Europe and in North America, where the virus has increased its activity in the recent years. No vaccines nor antiviral drugs are available for the prevention and
Inhibitors of Dengue virus and West Nile virus proteases based on the aminobenzamide scaffold.
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Dengue and West Nile viruses (WNV) are mosquito-borne members of flaviviruses that cause significant morbidity and mortality. There is no approved vaccine or antiviral drugs for human use to date. In this study, a series of functionalized meta and para aminobenzamide derivatives were synthesized and
Broad-spectrum catalytic metallopeptide inactivators of Zika and West Nile virus NS2B/NS3 proteases.
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Flaviviruses possess a conserved protease that is vital for viral maturation. We have designed catalytic metallopeptides for inactivation of both Zika and West Nile viral proteases, and potentially other viral homologues, by irreversible target destruction and low off-target activity against host
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