title: The calmodulin antagonist W-7 (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride) inhibits DENV infection in Huh-7 cells.
abstract: 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 DENV 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 DENV replication.
authors.affiliation: Departmento de Infectómica y Patogénesis Molecular, CINVESTAV-IPN, México, D.F. 07360, Mexico.
authors.forename: Patricia
authors.initials: P
authors.lastname: Bautista-Carbajal
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, 775555 TX, United States.
authors.forename: Ruben
authors.initials: R
authors.lastname: Soto-Acosta
authors.affiliation: Departmento de Infectómica y Patogénesis Molecular, CINVESTAV-IPN, México, D.F. 07360, Mexico.
authors.forename: Antonio H
authors.initials: AH
authors.lastname: Angel-Ambrocio
authors.affiliation: Departmento de Infectómica y Patogénesis Molecular, CINVESTAV-IPN, México, D.F. 07360, Mexico.
authors.forename: Margot
authors.initials: M
authors.lastname: Cervantes-Salazar
authors.affiliation: Departmento de Infectómica y Patogénesis Molecular, CINVESTAV-IPN, México, D.F. 07360, Mexico; Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, 775555 TX, United States.
authors.forename: Circe I
authors.initials: CI
authors.lastname: Loranca-Vega
authors.affiliation: Departmento de Infectómica y Patogénesis Molecular, CINVESTAV-IPN, México, D.F. 07360, Mexico; Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, 775555 TX, United States.
authors.forename: Mayra
authors.initials: M
authors.lastname: Herrera-Martínez
authors.affiliation: Departmento de Infectómica y Patogénesis Molecular, CINVESTAV-IPN, México, D.F. 07360, Mexico. Electronic address: rmangel@cinvestav.mx.
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Del Angel
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D002147:Calmodulin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D045744:Cell Line, Tumor; D003715:Dengue / Q000378:metabolism / Q000821:virology*; D003716:Dengue Virus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D011485:Protein Binding; D013449:Sulfonamides / Q000494:pharmacology*; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D002147:Calmodulin; D013449:Sulfonamides; D017361:Viral Nonstructural Proteins; C017967:W 7
keywords: Calmudulin (CaM); Dengue virus (DENV) infection; Replicative complexes; W7