Mutagenesis of D80-82 and G83 residues in West Nile Virus NS2B: Effects on NS2B-NS3 activity and viral replication
نویسندگان
چکیده
منابع مشابه
Development and characterization of new peptidomimetic inhibitors of the West Nile virus NS2B-NS3 protease.
A series of new substrate analogue inhibitors of the WNV NS2B-NS3 protease containing decarboxylated arginine mimetics at the P1 position was developed. Among the various analogues, trans-(4-guanidino)cyclohexylmethylamide (GCMA) was identified as the most suitable P1 residue. In combination with dichloro-substituted phenylacetyl groups at the P4 position, three inhibitors with inhibition const...
متن کاملThe two-component NS2B-NS3 proteinase represses DNA unwinding activity of the West Nile virus NS3 helicase.
Similar to many flavivirus types including Dengue and yellow fever viruses, the nonstructural NS3 multifunctional protein of West Nile virus (WNV) with an N-terminal serine proteinase domain and an RNA triphosphatase, an NTPase domain, and an RNA helicase in the C-terminal domain is implicated in both polyprotein processing and RNA replication and is therefore a promising drug target. To exhibi...
متن کاملNMR Analysis of the Dynamic Exchange of the NS2B Cofactor between Open and Closed Conformations of the West Nile Virus NS2B-NS3 Protease
BACKGROUND The two-component NS2B-NS3 proteases of West Nile and dengue viruses are essential for viral replication and established targets for drug development. In all crystal structures of the proteases to date, the NS2B cofactor is located far from the substrate binding site (open conformation) in the absence of inhibitor and lining the substrate binding site (closed conformation) in the pre...
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Dengue diseases have an economic as well as social burden worldwide. In this study, the antiviral activity of protegrin-1 (PG-1, RGGRLCYCRRRFCVCVGR) peptide towards dengue NS2B-NS3pro and viral replication in Rhesus monkey kidney (MK2) cells was investigated. The peptide PG-1 was synthesized by solid-phase peptide synthesis, and disulphide bonds formation followed by peptide purification was co...
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BACKGROUND Global resurgence of dengue virus infections in many of the tropical and subtropical countries is a major concern. Therefore, there is an urgent need for the development of successful drugs that are both economical and offer a long-lasting protection. The viral NS2B-NS3 serine protease (NS2B-NS3pro) is a promising target for the development of drug-like inhibitors, which are not avai...
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ژورنال
عنوان ژورنال: Virologica Sinica
سال: 2013
ISSN: 1674-0769,1995-820X
DOI: 10.1007/s12250-013-3276-y