Abstract
The mosquito-borne West Nile virus (WNV) causes a wide range of symptoms ranging from fever to the often fatal viral encephalitis. To date, no vaccine or drug therapy is available. The trypsin-like WNV NS2B-NS3 protease is deemed a plausible drug target and was shown to be inhibited by bovine pancreatic trypsin inhibitor (BPTI), a 58-residue protein isolated from bovine lung. Herein, we report a protein truncation study that resulted in a novel 14-residue cyclic peptide with equipotent inhibitory activity to native BPTI. We believe our truncation strategy can be further applied in the development of peptide-based inhibitors targeting trypsin-like proteases.
Keywords:
Aprotinin; BPTI; NS3 protease; West Nile virus; peptide.
MeSH terms
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Animals
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Cattle
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Crystallography, X-Ray
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Dose-Response Relationship, Drug
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Microbial Sensitivity Tests
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Models, Molecular
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Molecular Structure
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Protease Inhibitors / chemical synthesis
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Protease Inhibitors / chemistry
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Protease Inhibitors / pharmacology*
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RNA Helicases / antagonists & inhibitors
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RNA Helicases / metabolism
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Serine Endopeptidases / metabolism
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Structure-Activity Relationship
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Trypsin / metabolism
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Trypsin Inhibitors / chemical synthesis
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Trypsin Inhibitors / chemistry
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Trypsin Inhibitors / pharmacology*
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Viral Nonstructural Proteins / antagonists & inhibitors*
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Viral Nonstructural Proteins / metabolism
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West Nile virus / drug effects
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West Nile virus / enzymology*
Substances
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NS2B protein, flavivirus
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NS3 protein, flavivirus
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Protease Inhibitors
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Trypsin Inhibitors
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Viral Nonstructural Proteins
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Serine Endopeptidases
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Trypsin
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RNA Helicases