The calmodulin antagonist W-7 (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride) inhibits DENV infection in Huh-7 cells

被引：17

作者：

Bautista-Carbajal, Patricia ^{[1
]}

Soto-Acosta, Ruben ^{[2
]}

Angel-Ambrocio, Antonio H. ^{[1
]}

Cervantes-Salazar, Margot ^{[1
]}

Loranca-Vega, Circe I. ^{[1
,2
]}

Herrera-Martinez, Mayra ^{[1
,2
]}

del Angel, Rosa M. ^{[1
]}

机构：

[1] IPN, CINVESTAV, Dept Infect & Patogenesis Mol, Mexico City 07360, DF, Mexico

[2] Univ Texas Med Branch, Dept Biochem & Mol Biol, Galveston, TX USA

来源：

VIROLOGY | 2017年 / 501卷

关键词：

Dengue virus (DENV) infection; Calmudulin (CaM); W7; Replicative complexes; NONSTRUCTURAL PROTEIN NS2A; WEST-NILE-VIRUS; DENGUE VIRUS; ENDOPLASMIC-RETICULUM; NS2B-NS3; PROTEASE; BINDING DOMAIN; REPLICATION; CONSTRUCTION; GLYCOPROTEIN; DYNAMICS;

D O I：

10.1016/j.virol.2016.12.004

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Dengue virus (DENV) replicative cycle occurs in the endoplasmic reticulum where calcium ions play an important role in cell signaling. Calmodulin (CaM) is the primary sensor of intracellular Ca2+ levels in eukaryotic cells. In this paper, the effect of the calmodulin antagonist W-7 in DENV infection in Huh-7 cells was evaluated. W7 inhibited viral yield, NS1 secretion and viral RNA and protein synthesis. Moreover, luciferase activity, encoded by a DENY replicon, was also reduced. A decrease in the replicative complexes formation was clearly observed in W7 treated cells. Docking simulations suggest 2 possible mechanisms of action for W7: the direct inhibition of NS2B-NS3 activity and/or inhibition of the interaction between NS2A with Ca2+-CaM complex. This last possibility was supported by the in vitro interaction observed between recombinant NS2A and CaM. These results indicate that Ca2+-CaM plays an important role in DENY replication.

引用

页码：188 / 198

页数：11

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