Efavirenz Repurposing Challenges: A Novel Nanomicelle-Based Antiviral Therapy Against Mosquito-Borne Flaviviruses DOI Creative Commons
Sara Maldonado,

Pedro Fuentes,

Ezequiel Bernabeu

et al.

Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(2), P. 241 - 241

Published: Feb. 12, 2025

Background/Objective: World Health Organization latest statistics state that 17% of infectious diseases are transmitted by vectors, causing more than 700,000 deaths each year. Particularly, dengue (DENV), Zika (ZIKV) and yellow fever (YFV) viral infections have generated international awareness due to their epidemic proportion risks spread. In this framework, the repositioning strategy Efavirenz (EFV) represents a key clinical feature improve different antiviral therapies. Therefore, development Soluplus®-based nanomicelles (NMs) loaded with EFV (10 mg/mL) for optimized oral pharmacotherapy against ZIKV, DENV YFV was investigated. Methods: EFV-NMs were obtained an acetone diffusion technique. Micellar size in vitro micellar interaction mucin assessed dynamic light scattering. cytocompatibility investigated A549 Vero cells activity evaluated. vivo bioavailability histological studies Wistar rats. Results: encapsulation within Soluplus® NMs increased drug's apparent aqueous solubility up 4803-fold unimodal distribution ~90 nm at 25 37 °C. also pH range 1.2-7.5 its storage physicochemical stability 4 °C confirmed over 2 years. assays dispersions resulted safe nanoformulations. Interestingly, EFV-loaded exhibited significantly higher compared solution all tested flaviviruses. addition, selectivity index (SI) values reveal considerably biological efficacy cell lines infection (SI > 10). Further, drug pharmacokinetics parameters enhanced after administration NMs, being biocompatible not damage gastrointestinal segments. Conclusions: Overall, our nanoformulation highlighted potential as novel delivery platform therapy.

Language: Английский

Exploiting Host Kinases to Combat Dengue Virus Infection and Disease DOI Creative Commons
Natasha M. Bourgeois, Ling Wei, Alexis Kaushansky

et al.

Antiviral Research, Journal Year: 2025, Volume and Issue: unknown, P. 106172 - 106172

Published: May 1, 2025

Language: Английский

Citations

0

Exploring the Therapeutic Potential of Polygonum aviculare L. compounds against Dengue Virus through Computational Methods DOI

Zainab Irfan,

Sumaiya Tariq,

M. Sarwar

et al.

Journal of Herbal Medicine, Journal Year: 2025, Volume and Issue: unknown, P. 101027 - 101027

Published: May 1, 2025

Language: Английский

Citations

0

Artificial intelligence in anti-dengue drug development DOI Creative Commons
Miah Roney

Intelligent Pharmacy, Journal Year: 2024, Volume and Issue: 2(5), P. 721 - 722

Published: Feb. 1, 2024

Dengue fever is a mosquito-borne illness that affects millions of people worldwide. Artificial intelligence (AI) being employed in the battle against it. AI used to analyse dengue immune repertoires, which may yield hitherto unheard-of insights into complexities adaptive immunity, help development novel treatments, and influence creation vaccines. This AI-driven strategy contribute therapies are more potent.

Language: Английский

Citations

3

Antiviral actions of natural compounds against dengue virus RNA dependent RNA polymerase: insights from molecular dynamics and Gibbs free energy landscape DOI
Ali A. Rabaan, Nawal Al Kaabi,

Muzaheed Muzaheed

et al.

Journal of Biomolecular Structure and Dynamics, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 18

Published: March 5, 2024

Dengue fever, a major global health challenge, affects nearly half the world's population and lacks effective treatments or vaccines. Addressing this, our study focused on natural compounds that potentially inhibit dengue virus's RNA-dependent RNA polymerase (RdRp), crucial target in viral replication cycle. Utilizing MTiOpenScreen webserver, we screened 1226 from NP-lib database. This screening identified four promising ZINC000059779788, ZINC0000044404209, ZINC0000253504517 ZINC0000253499146), each demonstrating high negative binding energies between −10.4 −9.9 kcal/mol, indicative of strong potential as RdRp inhibitors. These underwent rigorous validation through re-docking detailed 100 ns molecular dynamics (MD) simulation. analysis affirmed dynamic stability protein-ligand complexes, critical factor effectiveness drug candidates. Additionally, conducted essential free energy landscape calculations to understand structural transitions protein upon ligand binding, providing valuable insights into mechanism inhibition. Our findings present these molecules therapeutic agents against virus. By targeting allosteric site RdRp, offer novel approach hinder process. research significantly contributes search for anti-dengue treatments, positioning key players virus control strategies.

Language: Английский

Citations

3

Efavirenz Repurposing Challenges: A Novel Nanomicelle-Based Antiviral Therapy Against Mosquito-Borne Flaviviruses DOI Creative Commons
Sara Maldonado,

Pedro Fuentes,

Ezequiel Bernabeu

et al.

Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(2), P. 241 - 241

Published: Feb. 12, 2025

Background/Objective: World Health Organization latest statistics state that 17% of infectious diseases are transmitted by vectors, causing more than 700,000 deaths each year. Particularly, dengue (DENV), Zika (ZIKV) and yellow fever (YFV) viral infections have generated international awareness due to their epidemic proportion risks spread. In this framework, the repositioning strategy Efavirenz (EFV) represents a key clinical feature improve different antiviral therapies. Therefore, development Soluplus®-based nanomicelles (NMs) loaded with EFV (10 mg/mL) for optimized oral pharmacotherapy against ZIKV, DENV YFV was investigated. Methods: EFV-NMs were obtained an acetone diffusion technique. Micellar size in vitro micellar interaction mucin assessed dynamic light scattering. cytocompatibility investigated A549 Vero cells activity evaluated. vivo bioavailability histological studies Wistar rats. Results: encapsulation within Soluplus® NMs increased drug's apparent aqueous solubility up 4803-fold unimodal distribution ~90 nm at 25 37 °C. also pH range 1.2-7.5 its storage physicochemical stability 4 °C confirmed over 2 years. assays dispersions resulted safe nanoformulations. Interestingly, EFV-loaded exhibited significantly higher compared solution all tested flaviviruses. addition, selectivity index (SI) values reveal considerably biological efficacy cell lines infection (SI > 10). Further, drug pharmacokinetics parameters enhanced after administration NMs, being biocompatible not damage gastrointestinal segments. Conclusions: Overall, our nanoformulation highlighted potential as novel delivery platform therapy.

Language: Английский

Citations

0