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The Importance of Epigallocatechin as a Scaffold for Drug Development against Flaviviruses.

ABSTRACT: Arboviruses such as Dengue, yellow fever, West Nile, and Zika are flaviviruses vector-borne RNA viruses transmitted biologically among vertebrate hosts by blood-taking vectors. Many flaviviruses are associated with neurological, viscerotropic, and hemorrhagic diseases, posing significant health and socioeconomic concerns as they adapt to new environments. Licensed drugs against them are currently unavailable, so searching for effective antiviral molecules is still necessary. Epigallocatechin molecules, a green tea polyphenol, have shown great virucidal potential against flaviviruses, including DENV, WNV, and ZIKV. The interaction of EGCG with the viral envelope protein and viral protease, mainly identified by computational studies, describes the interaction of these molecules with viral proteins; however, how the viral NS2B/NS3 protease interacts with epigallocatechin molecules is not yet fully deciphered. Consequently, we tested the antiviral potential of two epigallocatechin molecules (EGC and EGCG) and their derivative (AcEGCG) against DENV, YFV, WNV, and ZIKV NS2B/NS3 protease. Thus, we assayed the effect of the molecules and found that a mixture of the molecules EGC (competitive) and EGCG (noncompetitive) inhibited the virus protease of YFV, WNV, and ZIKV more effectively with IC₅₀ values of 1.17 ± 0.2 µM, 0.58 ± 0.07 µM, and 0.57 ± 0.05 µM, respectively. As these molecules fundamentally differ in their inhibitory mode and chemical structure, our finding may open a new line for developing more effective allosteric/active site inhibitors to combat flaviviruses infection.

SUBMITTER: Coronado MA

PROVIDER: S-EPMC10053286 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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The Importance of Epigallocatechin as a Scaffold for Drug Development against Flaviviruses.

Coronado Mônika A MA Gering Ian I Sevenich Marc M Olivier Danilo S DS Mastalipour Mohammadamin M Amaral Marcos S MS Willbold Dieter D Eberle Raphael J RJ

Pharmaceutics 20230301 3

Arboviruses such as Dengue, yellow fever, West Nile, and Zika are flaviviruses vector-borne RNA viruses transmitted biologically among vertebrate hosts by blood-taking vectors. Many flaviviruses are associated with neurological, viscerotropic, and hemorrhagic diseases, posing significant health and socioeconomic concerns as they adapt to new environments. Licensed drugs against them are currently unavailable, so searching for effective antiviral molecules is still necessary. Epigallocatechin mol ...[more]

PMID: 36986663

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Project description:The Flaviviridae are a family of positive-sense, single-stranded RNA enveloped viruses, and their members belong to a single genus, Flavivirus. Flaviviruses are found in mosquitoes and ticks; they are etiological agents of: dengue fever, Japanese encephalitis, West Nile virus infection, Zika virus infection, tick-borne encephalitis, and yellow fever, among others. Only a few flavivirus vaccines have been licensed for use in humans: yellow fever, dengue fever, Japanese encephalitis, tick-borne encephalitis, and Kyasanur forest disease. However, improvement is necessary in vaccination strategies and in understanding of the immunological mechanisms involved either in the infection or after vaccination. This is especially important in dengue, due to the immunological complexity of its four serotypes, cross-reactive responses, antibody-dependent enhancement, and immunological interference. In this context, mucosal vaccines represent a promising alternative against flaviviruses. Mucosal vaccination has several advantages, as inducing long-term protective immunity in both mucosal and parenteral tissues. It constitutes a friendly route of antigen administration because it is needle-free and allows for a variety of antigen delivery systems. This has promoted the development of several ways to stimulate immunity through the direct administration of antigens (e.g., inactivated virus, attenuated virus, subunits, and DNA), non-replicating vectors (e.g., nanoparticles, liposomes, bacterial ghosts, and defective-replication viral vectors), and replicating vectors (e.g., Salmonella enterica, Lactococcus lactis, Saccharomyces cerevisiae, and viral vectors). Because of these characteristics, mucosal vaccination has been explored for immunoprophylaxis against pathogens that enter the host through mucosae or parenteral areas. It is suitable against flaviviruses because this type of immunization can stimulate the parenteral responses required after bites from flavivirus-infected insects. This review focuses on the advantages of mucosal vaccine candidates against the most relevant flaviviruses in either humans or animals, providing supporting data on the feasibility of this administration route for future clinical trials.

Dataset Information

The Importance of Epigallocatechin as a Scaffold for Drug Development against Flaviviruses.

Publications

The Importance of Epigallocatechin as a Scaffold for Drug Development against Flaviviruses.

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