NS2B3 cleaves polyprotein

Stable Identifier
R-HSA-9918817
Type
Reaction [transition]
Species
Homo sapiens
Related Species
Dengue virus type 2
Compartment
endoplasmic reticulum membrane
ReviewStatus
5/5
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NS2B3 cleaves polyprotein
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NS2B:NS3 (NS2B3) peptidase cleaves the Dengue virus polyprotein, producing the C-prM-E-NS1-NS2A fragment, NS2B and the NS345 fragment ((Preugschat et al., 1990; Preugschat & Strauss, 1991, Bera et al., 2007; Shiryaev et al., 2007).

Bortezomib is a proteasome inhibitor drug, approved for the treatment of cancer. In studies by Ci et al. (2023) using human (HEK293T, HeLa, Huh-7) and hamster (BHK-21) cell lines with ZIKV (strain FSS13025) and DENV (strain DENV2_China_SZ_2015), Bortezomib was found to impair NS2B3 protease activity. It induces the ubiquitination and aggregation of NS3 protein via the ERAD pathway, leading to impaired NS3 protease function and thereby interfering with viral polyprotein cleavage (Ci et al., 2023).

Several approved compounds inhibit NS2B3 activity in vitro. See the binding reaction for details.
Literature References
PubMed ID Title Journal Year
17337448 Functional characterization of cis and trans activity of the Flavivirus NS2B-NS3 protease

Bera, AK, Kuhn, RJ, Smith, JL

J Biol Chem 2007
17067286 Cleavage preference distinguishes the two-component NS2B-NS3 serine proteinases of Dengue and West Nile viruses

Shiryaev, SA, Kozlov, IA, Ratnikov, BI, Smith, JW, Lebl, M, Strongin, AY

Biochem J 2007
1683727 Processing of nonstructural proteins NS4A and NS4B of dengue 2 virus in vitro and in vivo

Preugschat, F, Strauss, JH

Virology 1991
2143543 In vitro processing of dengue virus type 2 nonstructural proteins NS2A, NS2B, and NS3

Preugschat, F, Yao, CW, Strauss, JH

J Virol 1990
36351431 Bortezomib inhibits ZIKV/DENV by interfering with viral polyprotein cleavage via the ERAD pathway

Ci, Y, Yao, B, Yue, K, Yang, Y, Xu, C, Li, DF, Qin, CF, Shi, L

Cell Chem Biol 2023
Participants
Input
Output
Participates
as an event of
Catalyst Activity

serine-type endopeptidase activity of NS2B3 [cytosol]

Physical Entity
NS2B3 [cytosol] (Dengue virus type 2)
Activity
serine-type endopeptidase activity (GO:0004252)
This event is regulated
Negatively by
Regulator
bortezomib [cytosol]
Regulator
NS2B3:Dengue protease inhibitor [cytosol] (Dengue virus type 2)
Disease
Name Identifier Synonyms
dengue disease DOID:12205 breakbone fever, Dengue Fever, classic dengue
Cross References
Mondo
Authored
Stephan, R  (2024-08-18)
Reviewed
Mansur, DS  (2025-09-18)
Roque Ascenção, F  (2025-10-29)
Created
Stephan, R  (2024-08-18)
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