| 2020 | Larvicidal Activity of Cinnamic Acid Derivatives: Investigating Alternative Products for L. Control. | Molecules | The mosquito transmits the virus that causes dengue, yellow fever, Zika and Chikungunya viruses, and in several regions of the planet represents a vector of great clinical importance. In terms of mortality and morbidity, infections caused by are among the most serious arthropod transmitted viral diseases. The present study investigated the larvicidal potential of seventeen cinnamic acid derivatives against fourth stage larvae. The larvicide assays were performed using larval mortality rates to determine lethal concentration (LC). Compounds containing the medium alkyl chains butyl cinnamate () and pentyl cinnamate () presented excellent larvicidal activity with LC values of around 0.21-0.17 mM, respectively. While among the derivatives with aryl substituents, the best LC result was 0.55 mM for benzyl cinnamate (). The tested derivatives were natural compounds and in pharmacology and antiparasitic studies, many have been evaluated using biological models for environmental and toxicological safety. Molecular modeling analyses suggest that the larvicidal activity of these compounds might be due to a multi-target mechanism of action involving inhibition of a carbonic anhydrase (CA), a histone deacetylase (HDAC2), and two sodium-dependent cation-chloride co-transporters (CCC2 e CCC3). |
| 2015 | Alterations of Nuclear Architecture and Epigenetic Signatures during African Swine Fever Virus Infection. | Viruses | Viral interactions with host nucleus have been thoroughly studied, clarifying molecular mechanisms and providing new antiviral targets. Considering that African swine fever virus (ASFV) intranuclear phase of infection is poorly understood, viral interplay with subnuclear domains and chromatin architecture were addressed. Nuclear speckles, Cajal bodies, and promyelocytic leukaemia nuclear bodies (PML-NBs) were evaluated by immunofluorescence microscopy and Western blot. Further, efficient PML protein knockdown by shRNA lentiviral transduction was used to determine PML-NBs relevance during infection. Nuclear distribution of different histone H3 methylation marks at lysine's 9, 27 and 36, heterochromatin protein 1 isoforms (HP1α, HPβ and HPγ) and several histone deacetylases (HDACs) were also evaluated to assess chromatin status of the host. Our results reveal morphological disruption of all studied subnuclear domains and severe reduction of viral progeny in PML-knockdown cells. ASFV promotes H3K9me3 and HP1β foci formation from early infection, followed by HP1α and HDAC2 nuclear enrichment, suggesting heterochromatinization of host genome. Finally, closeness between DNA damage response factors, disrupted PML-NBs, and virus-induced heterochromatic regions were identified. In sum, our results demonstrate that ASFV orchestrates spatio-temporal nuclear rearrangements, changing subnuclear domains, relocating Ataxia Telangiectasia Mutated Rad-3 related (ATR)-related factors and promoting heterochromatinization, probably controlling transcription, repressing host gene expression, and favouring viral replication. |