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

Patricia Bautista-Carbajal, Ruben Soto-Acosta, Antonio H. Angel-Ambrocio, Margot Cervantes-Salazar, Circe I. Loranca-Vega, Mayra Herrera-Martínez, Rosa M. del Angel

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)188-198
Number of pages11
JournalVirology
Volume501
DOIs
StatePublished - Jan 15 2017

Fingerprint

Dengue Virus
Virus Diseases
Calmodulin
Replicon
Viral RNA
Eukaryotic Cells
Viral Proteins
Virus Replication
Luciferases
Endoplasmic Reticulum
W 7
Ions
Calcium

Keywords

  • Calmudulin (CaM)
  • Dengue virus (DENV) infection
  • Replicative complexes
  • W7

ASJC Scopus subject areas

  • Virology

Cite this

Bautista-Carbajal, P., Soto-Acosta, R., Angel-Ambrocio, A. H., Cervantes-Salazar, M., Loranca-Vega, C. I., Herrera-Martínez, M., & del Angel, R. M. (2017). The calmodulin antagonist W-7 (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride) inhibits DENV infection in Huh-7 cells. Virology, 501, 188-198. https://doi.org/10.1016/j.virol.2016.12.004

The calmodulin antagonist W-7 (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride) inhibits DENV infection in Huh-7 cells. / Bautista-Carbajal, Patricia; Soto-Acosta, Ruben; Angel-Ambrocio, Antonio H.; Cervantes-Salazar, Margot; Loranca-Vega, Circe I.; Herrera-Martínez, Mayra; del Angel, Rosa M.

In: Virology, Vol. 501, 15.01.2017, p. 188-198.

Research output: Contribution to journalArticle

Bautista-Carbajal, P, Soto-Acosta, R, Angel-Ambrocio, AH, Cervantes-Salazar, M, Loranca-Vega, CI, Herrera-Martínez, M & del Angel, RM 2017, 'The calmodulin antagonist W-7 (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride) inhibits DENV infection in Huh-7 cells', Virology, vol. 501, pp. 188-198. https://doi.org/10.1016/j.virol.2016.12.004
Bautista-Carbajal P, Soto-Acosta R, Angel-Ambrocio AH, Cervantes-Salazar M, Loranca-Vega CI, Herrera-Martínez M et al. The calmodulin antagonist W-7 (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride) inhibits DENV infection in Huh-7 cells. Virology. 2017 Jan 15;501:188-198. https://doi.org/10.1016/j.virol.2016.12.004
Bautista-Carbajal, Patricia ; Soto-Acosta, Ruben ; Angel-Ambrocio, Antonio H. ; Cervantes-Salazar, Margot ; Loranca-Vega, Circe I. ; Herrera-Martínez, Mayra ; del Angel, Rosa M. / The calmodulin antagonist W-7 (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride) inhibits DENV infection in Huh-7 cells. In: Virology. 2017 ; Vol. 501. pp. 188-198.
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