Avaliação do teor de geranina como marcador de um derivado vegetal de Spondias mombin L. e do seu potencial efeito antiherpético
The herpes simplex virus type-1 (HSV-1) promotes a permanent infection of high prevalence in adults, with potential implications in immunocompromised individuals. Standard therapy for the treatment of symptoms of HSV infections includes acyclovir and its analogues, which have the same mechanism o...
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Formato: | doctoralThesis |
Idioma: | pt_BR |
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Universidade Federal do Rio Grande do Norte
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Endereço do item: | https://repositorio.ufrn.br/handle/123456789/32776 |
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Resumo: | The herpes simplex virus type-1 (HSV-1) promotes a permanent infection of high
prevalence in adults, with potential implications in immunocompromised individuals.
Standard therapy for the treatment of symptoms of HSV infections includes acyclovir
and its analogues, which have the same mechanism of action, act by inhibiting the DNA
polymerase enzyme involved in the synthesis of new virions in the infected cell.
Medicinal plants have shown promising antiviral effect as Spondias mombin species
(Anacardiaceae), popularly known as cajazeira, is a fruitful plant, distributed in Brazil
and other countries in the Americas. S. mombin presents non-clinical evidence of
antiviral effect, added to popular use to treat herpes. Its antiviral action is mainly related
to the presence of hydrolyzable tannins which act against HSV-1 and coxsakie virus,
and one of the bioactive metabolites appears to be geraniin. In this sense, this study
aimed to investigate the mechanism of antiviral action of the extract and fractions of the
leaves of S. mombin and geraniin against HSV-1, as well as to identify the substances
present in the extract and quantify the content of geraniin. For this, the phytochemical
profile of the extract by LC-MS and the geraniin content was quantified by a method
developed and validated by UFLC-DAD. For biological assays, different concentrations
of samples were used to evaluate the in vitro antiherpes activity (anti-HSV-1) in
virucidal, post-infection, attachment, and penetration assays. The mechanism of action
of geraniin was investigated considering the glycoproteins gB and gD of HSV-1 surface
as potential molecular targets. Molecular docking simulations were carried out for both
in order to determine the possible binding mode position of geraniin at the activity sites.
The binding mode position was posteriorly optimized considering the flexibility of the
glycoproteins. The chemical analysis of samples was performed by LC‑MS and
revealed the presence of 22 substances, which are hydrolysable tannins, O-glycosylated
flavonoids, phenolic acids, and a carbohydrate. The extract, tannin-rich fraction and
geraniin showed important in vitro virucidal activity through blocking viral attachment
but showed no relevant inhibition of viral penetration. The in silico approaches
demonstrated a high number of potential strong intermolecular interactions as hydrogen
bonds between geraniin and the activity site of the glycoproteins, particularly the
glycoprotein gB. In silico experiments indicated that geraniin is at least partially
responsible for the anti-herpes activity through interaction with the viral surface
glycoprotein gB, which is responsible for viral adsorption. Additionally, the quantitative
analyses of geraniin in the extract by UFLC-DAD presents a content of 193.8 µg of
geraniin per mg of extract. These results highlight the therapeutic potential of S.
mombin antiherpes treatment and provides support for its popular purposes. However,
further studies are required to validate the antiviral activities in vivo, as well as efficacy
in humans. |
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