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, Rubén; Ángel-Ambrocio, Antonio H.; Cervantes-Salazar, Margot; Loranca-Vega, Circe I.; Herrera-Martínez, Mayra; Ángel, Rosa M. del

doi:10.1016/j.virol.2016.12.004

Cited by 16 publications

(9 citation statements)

References 39 publications

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“…Alprazolam and dilazep found to be effective in Influenza Virus Infection and HIV, respectively, and danaprevir is a hepatitis C virus protease inhibitor (Freire-Garabal et al, 1993;Zeng et al, 2014;Gane et al, 2014). Apart from that, the calmodulin antagonist and topoisomerase I inhibitor have reported antiviral activity against the Dengue virus and HIV infection (Bautista-Carbajal, 2017;Showalter & Blair, 2016). Therapeutically targeting the kinases such as PI3K and P38 kinase found to be useful in viral infection (Wu et al, 2015, Griego et al, 2000.…”

Section: Discussionmentioning

confidence: 99%

Host transcriptome-guided drug repurposing for COVID-19 treatment: a meta-analysis based approach

Loganathan

Ramachandran

Shankaran

et al. 2020

PeerJ

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Background Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been declared a pandemic by the World Health Organization, and the identification of effective therapeutic strategy is a need of the hour to combat SARS-CoV-2 infection. In this scenario, the drug repurposing approach is widely used for the rapid identification of potential drugs against SARS-CoV-2, considering viral and host factors. Methods We adopted a host transcriptome-based drug repurposing strategy utilizing the publicly available high throughput gene expression data on SARS-CoV-2 and other respiratory infection viruses. Based on the consistency in expression status of host factors in different cell types and previous evidence reported in the literature, pro-viral factors of SARS-CoV-2 identified and subject to drug repurposing analysis based on DrugBank and Connectivity Map (CMap) using the web tool, CLUE. Results The upregulated pro-viral factors such as TYMP, PTGS2, C1S, CFB, IFI44, XAF1, CXCL2, and CXCL3 were identified in early infection models of SARS-CoV-2. By further analysis of the drug-perturbed expression profiles in the connectivity map, 27 drugs that can reverse the expression of pro-viral factors were identified, and importantly, twelve of them reported to have anti-viral activity. The direct inhibition of the PTGS2 gene product can be considered as another therapeutic strategy for SARS-CoV-2 infection and could suggest six approved PTGS2 inhibitor drugs for the treatment of COVID-19. The computational study could propose candidate repurposable drugs against COVID-19, and further experimental studies are required for validation.

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Section: Discussionmentioning

confidence: 99%

Host transcriptome-guided drug repurposing for COVID-19 treatment: a meta-analysis based approach

Loganathan

Ramachandran

Shankaran

et al. 2020

PeerJ

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“…A calmodulin inhibitor W7 was reported to exhibit anti-dengue activity in a cellbased assay. The mechanism of action of this inhibitor may be due to its interaction with calmodulin which interacts with NS2A's calmodulin binding motif [136]. Although W7 could disrupt calmodulin and NS2A interactions, no compound optimization was carried The membrane topology of NS4B was obtained using biochemical analysis.…”

Section: Ns2a Inhibitorsmentioning

confidence: 99%

Structures and Dynamics of Dengue Virus Nonstructural Membrane Proteins

Kang

2022

Membranes

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Dengue virus is an important human pathogen threating people, especially in tropical and sub-tropical regions. The viral genome has one open reading frame and encodes one polyprotein which can be processed into structural and nonstructural (NS) proteins. Four of the seven nonstructural proteins, NS2A, NS2B, NS4A and NS4B, are membrane proteins. Unlike NS3 or NS5, these proteins do not harbor any enzymatic activities, but they play important roles in viral replication through interactions with viral or host proteins to regulate important pathways and enzymatic activities. The location of these proteins on the cell membrane and the functional roles in viral replication make them important targets for antiviral development. Indeed, NS4B inhibitors exhibit antiviral activities in different assays. Structural studies of these proteins are hindered due to challenges in crystallization and the dynamic nature of these proteins. In this review, the function and membrane topologies of dengue nonstructural membrane proteins are presented. The roles of solution NMR spectroscopy in elucidating the structure and dynamics of these proteins are introduced. The success in the development of NS4B inhibitors proves that this class of proteins is an attractive target for antiviral development.

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“…51 There have been no efforts to date to develop inhibitors of NS2A; however, a known calmodulin inhibitor has been shown to inhibit the dengue virus. 51,52 The NS2B protein is a hydrophobic protein that serves as a cofactor to the NS3 protease. 53 NS2B has not been validated as an independent drug target, but only when in combination with NS3.…”

Section: ■ Viral Life Cyclesmentioning

confidence: 99%

“…During Dengue infection the viral protein NS2A interacts with calmodulin. A synthetic calmodulin inhibitor was shown to inhibit virus production, 52 suggesting that natural products that are calmodulin inhibitors could also be useful. In fact, plants and fungi have been a rich source of structurally diverse calmodulin inhibitors, and these should be further evaluated for their anti-Dengue effects.…”

Section: A Viral Proteinsmentioning

confidence: 99%

Natural Products with Potential to Treat RNA Virus Pathogens Including SARS-CoV-2

et al. 2020

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Three families of RNA viruses, the Coronaviridae , Flaviviridae , and Filoviridae , collectively have great potential to cause epidemic disease in human populations. The current SARS-CoV-2 ( Coronaviridae ) responsible for the COVID-19 pandemic underscores the lack of effective medications currently available to treat these classes of viral pathogens. Similarly, the Flaviviridae , which includes such viruses as Dengue, West Nile, and Zika, and the Filoviridae , with the Ebola-type viruses, as examples, all lack effective therapeutics. In this review, we present fundamental information concerning the biology of these three virus families, including their genomic makeup, mode of infection of human cells, and key proteins that may offer targeted therapies. Further, we present the natural products and their derivatives that have documented activities to these viral and host proteins, offering hope for future mechanism-based antiviral therapeutics. By arranging these potential protein targets and their natural product inhibitors by target type across these three families of virus, new insights are developed, and crossover treatment strategies are suggested. Hence, natural products, as is the case for other therapeutic areas, continue to be a promising source of structurally diverse new anti-RNA virus therapeutics.

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

Cited by 16 publications

References 39 publications

Host transcriptome-guided drug repurposing for COVID-19 treatment: a meta-analysis based approach

Host transcriptome-guided drug repurposing for COVID-19 treatment: a meta-analysis based approach

Structures and Dynamics of Dengue Virus Nonstructural Membrane Proteins

Natural Products with Potential to Treat RNA Virus Pathogens Including SARS-CoV-2

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