NS5 localizes to nucleus

Stable Identifier
R-HSA-9919966
Type
Reaction [uncertain]
Species
Homo sapiens
Related Species
Dengue virus type 2
Compartment
cytosol, nucleoplasm
ReviewStatus
5/5
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NS5 localizes to nucleus
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Dengue virus NS5 protein is found predominantly in the nucleus, although distribution is quite varied at a given time (Tay et al., 2013). NS5 nuclear import may be mediated by importin-beta (Johansson et al., 2001; Rawlinson et al., 2009; Tay & Vasudevan, 2018).

Ivermectin is a macrocyclic drug that is approved against onchocerciasis and other parasitic diseases. It binds the alpha subunit of the importin heterodimer (IMPα/β1) to dissociate it, and to free IMPα to prevent it binding to IMPβ1. This blocks nuclear import, specifically of host and viral proteins that have a classical nuclear localization signal (cNLS) motif (Wagstaff et al., 2012; Tay et al., 2013; Yang et al., 2020; reviewed in Jans & Wagstaff, 2020). In a clinical phase 2/3 trial (N=203) ivermectin accelerated NS1 antigenemia clearance in symptomatic dengue patients (Suputtamongkol et al., 2021). However, clinical efficacy of ivermectin was not observed, with the cited study suggesting that factors including patient population heterogeneity, ivermectin dosage, and the timing of treatment initiation relative to illness onset might have contributed to this finding (Suputtamongkol et al., 2021).
Literature References
PubMed ID Title Journal Year
29845531 The Transactions of NS3 and NS5 in Flaviviral RNA Replication

Tay, MYF, Vasudevan, SG

Adv Exp Med Biol 2018
23769930 Nuclear localization of dengue virus (DENV) 1-4 non-structural protein 5; protection against all 4 DENV serotypes by the inhibitor Ivermectin

Tay, MY, Fraser, JE, Chan, WK, Moreland, NJ, Rathore, AP, Wang, C, Vasudevan, SG, Jans, DA

Antiviral Res 2013
32942671 Ivermectin as a Broad-Spectrum Host-Directed Antiviral: The Real Deal?

Jans, DA, Wagstaff, KM

Cells 2020
19297323 CRM1-mediated nuclear export of dengue virus RNA polymerase NS5 modulates interleukin-8 induction and virus production

Rawlinson, SM, Pryor, MJ, Wright, PJ, Jans, DA

J Biol Chem 2009
22417684 Ivermectin is a specific inhibitor of importin α/β-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus

Wagstaff, KM, Sivakumaran, H, Heaton, SM, Harrich, D, Jans, DA

Biochem J 2012
11257177 A small region of the dengue virus-encoded RNA-dependent RNA polymerase, NS5, confers interaction with both the nuclear transport receptor importin-beta and the viral helicase, NS3

Johansson, M, Brooks, AJ, Jans, DA, Vasudevan, SG

J Gen Virol 2001
33462580 Ivermectin Accelerates Circulating Nonstructural Protein 1 (NS1) Clearance in Adult Dengue Patients: A Combined Phase 2/3 Randomized Double-blinded Placebo Controlled Trial

Suputtamongkol, Y, Avirutnan, P, Mairiang, D, Angkasekwinai, N, Niwattayakul, K, Yamasmith, E, Saleh-Arong, FA, Songjaeng, A, Prommool, T, Tangthawornchaikul, N, Puttikhunt, C, Hunnangkul, S, Komoltri, C, Thammapalo, S, Malasit, P

Clin Infect Dis 2021
32135219 The broad spectrum antiviral ivermectin targets the host nuclear transport importin α/β1 heterodimer

Yang, SNY, Atkinson, SC, Wang, C, Lee, A, Bogoyevitch, MA, Borg, NA, Jans, DA

Antiviral Res 2020
Participants
Input
Output
Participates
as an event of
Event Information
Go Biological Process
protein localization to nucleoplasm (1990173)
This event is regulated
Negatively by
Regulator
Importin alpha:Ivermectin [cytosol] (Homo sapiens)
Requirements
Disease
Name Identifier Synonyms
dengue disease DOID:12205 breakbone fever, Dengue Fever, classic dengue
Cross References
Mondo
Authored
Stephan, R  (2024-08-19)
Reviewed
Mansur, DS  (2025-09-18)
Roque Ascenção, F  (2025-10-29)
Created
Stephan, R  (2024-08-29)
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