ArticleThe Biochemical journal2006
Cleavage targets and the D-arginine-based inhibitors of the West Nile virus NS3 processing proteinase.
Article in The Biochemical journal, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
46 citing papers in PubMed, 95 citations in OpenAlex.
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- Drugs for the Treatment of Zika Virus Infection.Journal of medicinal chemistry · 2020Review
- Proteases from dengue, West Nile and Zika viruses as drug targets.Biophysical reviews · 2019Review
- Strategies Towards Protease Inhibitors for Emerging Flaviviruses.Advances in experimental medicine and biology · 2018Review
- Effects of NS2B-NS3 protease and furin inhibition on West Nile and Dengue virus replication.Journal of enzyme inhibition and medicinal chemistry · 2017Article
- Characterization of the Zika virus two-component NS2B-NS3 protease and structure-assisted identification of allosteric small-molecule antagonists.Antiviral research · 2017Article
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- Mechanisms of activation and inhibition of Zika virus NS2B-NS3 protease.Cell research · 2016Article
- An Overview of Current Approaches Toward the Treatment and Prevention of West Nile Virus Infection.Methods in molecular biology (Clifton, N.J.) · 2016Article
- Policresulen, a novel NS2B/NS3 protease inhibitor, effectively inhibits the replication of DENV2 virus in BHK-21 cells.Acta pharmacologica Sinica · 2015Article
- Context-Dependent Cleavage of the Capsid Protein by the West Nile Virus Protease Modulates the Efficiency of Virus Assembly.Journal of virology · 2015Article
- Article
- Generation of West Nile virus infectious clones containing amino acid insertions between capsid and capsid anchor.Viruses · 2014Article
- Discovery of potential drugs for human-infecting H7N9 virus containing R294K mutation.Drug design, development and therapy · 2014Article
- West Nile virus drug discovery.Viruses · 2013Review
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Mosquito-borne WNV (West Nile virus) is an emerging global threat. The NS3 proteinase, which is essential for the proteolytic processing of the viral polyprotein precursor, is a promising drug target. We have isolated and biochemically characterized the recombinant, highly active NS3 proteinase. We have determined that the NS3 proteinase functions in a manner that is distantly similar to furin in cleaving the peptide and protein substrates. We determined that aprotinin and D-arginine-based 9-12-mer peptides are potent inhibitors of WNV NS3 with K(i) values of 26 nM and 1 nM respectively. Consistent with the essential role of NS3 activity in the life cycle of WNV and with the sensitivity of NS3 activity to the D-arginine-based peptides, we showed that nona-D-Arg-NH2 reduced WNV infection in primary neurons. We have also shown that myelin basic protein, a deficiency of which is linked to neurological abnormalities of the brain, is sensitive to NS3 proteolysis in vitro and therefore this protein represents a convenient test substrate for the studies of NS3. A three-dimensional model of WNV NS3 that we created may provide a structural guidance and a rationale for the subsequent design of fine-tuned inhibitors. Overall, our findings represent a foundation for in-depth mechanistic and structural studies as well as for the design of novel and efficient inhibitors of WNV NS3.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.