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Details on Person The NS3 subunit of the DENV replication complex unwinds vira...

Class:IdSummation:9923526
_displayNameThe NS3 subunit of the DENV replication complex unwinds vira...
_timestamp2025-09-15 08:06:11
created[InstanceEdit:9923534] Stephan, Ralf, 2024-10-01
modified[InstanceEdit:9925587] Stephan, Ralf, 2024-10-18
[InstanceEdit:9945288] Stephan, Ralf, 2025-04-13
[InstanceEdit:9946397] Stephan, Ralf, 2025-04-24
[InstanceEdit:9946476] Stephan, Ralf, 2025-04-25
[InstanceEdit:9954389] Stephan, Ralf, 2025-06-07
[InstanceEdit:9955740] Stephan, Ralf, 2025-06-11
[InstanceEdit:9966302] Stephan, Ralf, 2025-09-15
textThe NS3 subunit of the DENV replication complex unwinds viral RNA and melts its secondary structures. This activity, demonstrated with NS3 from various DENV serotypes (e.g., DENV-2, DENV-3, DENV-4), is fueled by the hydrolysis of nucleoside triphosphates (mainly ATP) and occurs in the presence of Mn2+ or Mg2+ ions (Swarbrick et al., 2017; Xu et al., 2005; Incicco et al., 2023; Osawa et al., 2023; reviewed in van den Elsen et al., 2021). Interactions of NS3 with other viral proteins within the replication complex modulate its helicase activity. For example, NS5 stimulates the NTPase activity of DENV-1 NS3 (Cui et al., 1998). The NS3-NS5 interaction has been shown to be crucial for efficient DENV-2 replication in human (Huh-7), hamster (BHK-21), and mosquito (C6/36) cells (Tay et al., 2015). Furthermore, in vitro studies with DENV-1 proteins show that interaction with NS4B enhances NS3 helicase activity (Kundharapu & Chowdary, 2022).

Ivermectin is an approved antiparasitic drug that inhibits RNA unwinding non-competitively, as well as DENV, West-Nile virus (WNV), and Yellow Fever virus (YFV) replication in vitro (Mastrangelo e al., 2012). Micafungin is an approved antifungal drug that inhibits NS3 helicase activity, reducing DENV proliferation in cells and an animal model (Kim et al., 2021).
(summation)[BlackBoxEvent:9922957] NS3 melts (+)-RNA secondary structures [Homo sapiens]
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