Publications by authors named "Claudio C Cirne-Santos"

Article Synopsis
  • - The study focused on creating and analyzing new coumarin-imidazopyridine hybrid ligands and their zinc(II) complexes, achieving a successful synthesis with yields between 56-90%.
  • - The synthesized complexes showed significant antiviral effects against the Zika virus, with some demonstrating better activity than the standard antiviral ribavirin.
  • - Investigations into how these compounds work revealed they can disrupt both viral entry and replication, providing insights into their mechanisms and potential for further development.
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Introduction: Zika virus (ZIKV) is a flavivirus transmitted through the bites of infected Aedes mosquitoes. These viruses can also be transmitted through sexual contact, vertical transmission, and possibly transfusion. Most cases are asymptomatic, but symptoms can include rash, conjunctivitis, fever, and arthralgia, which are characteristic of other arboviruses.

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The CCCH-type zinc finger antiviral protein (ZAP) in humans, specifically isoforms ZAP-L and ZAP-S, is a crucial component of the cell's intrinsic immune response. ZAP acts as a post-transcriptional RNA restriction factor, exhibiting its activity during infections caused by retroviruses and alphaviruses. Its function involves binding to CpG (cytosine-phosphate-guanine) dinucleotide sequences present in viral RNA, thereby directing it towards degradation.

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Article Synopsis
  • - The study focuses on evaluating new quinolone derivatives as potential antiviral agents against herpes simplex virus (HSV) due to the emergence of resistant strains.
  • - In vitro tests showed that these compounds effectively inhibited HSV replication, particularly by suppressing ICP27 viral protein expression, with EC values ranging from 8 μM to 32 μM, and highlighted the importance of specific chemical structures for effectiveness.
  • - While these new derivatives exhibited lower antiviral activity than acyclovir, they demonstrated unique mechanisms of action, warranting further pre-clinical research to develop these agents as alternative HSV treatments.
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Zika virus (ZIKV) is an arthropod-borne flavivirus that reemerged in 2007 and, since then, has caused several outbreaks and spread to over 80 countries worldwide. Along with this, ZIKV infections have been associated with severe clinical outcomes, including neurological manifestations, especially in newborns, posing a major threat to human health. However, there are no licensed vaccines or specific antiviral agents available yet; thereby, there is an urgent need for the discovery of novel therapeutic strategies to fight this infection.

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Article Synopsis
  • The increasing prevalence of Zika and Chikungunya viruses, coupled with a lack of vaccines and antiviral treatments, highlights the need for new therapeutic approaches, particularly using natural compounds.
  • Research on the marine brown seaweed Canistrocarpus cervicornis demonstrated its potential antiviral properties, showing that its crude extract and an isolated compound called dolastane both effectively inhibit ZIKV and CHIKV infections in Vero cells.
  • Dolastane proved to be significantly more effective than the crude extract and a control antiviral, ribavirin, achieving around 90% reduction in infectivity for CHIKV and 64% for ZIKV, suggesting promising applications for this seaweed-derived compound in future antiviral strategies.
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This work reports the synthesis of quinolone-N-acylhydrazone hybrids, namely 6-R-N'-(2-hydxoxybenzylidene)-4-oxo-1,4-dihydroquinoline-3-carbohydrazide (R = H: 5a, F: 5b, Cl: 5c and Br: 5d), which exhibited excellent activity against arbovirus Zika (ZIKV) and Chikungunya (CHIKV). In vitro screening towards ZIKV and CHIKV inhibition revealed that all substances have significant antiviral activity, most of them being more potent than standard Ribavirin (5a-d: EC = 0.75-0.

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Article Synopsis
  • Chikungunya virus (CHIKV) is a re-emerging disease with no specific antiviral treatment, posing a serious public health threat.
  • Blood samples from patients displayed CHIKV symptoms, leading to the successful isolation of 3 virus strains which were characterized through sequencing to assess their similarity to recent Brazilian outbreaks.
  • Seaweed extracts showed significant antiviral effects against CHIKV, with specific extracts demonstrating low toxicity and optimal inhibition when added to infected cells within 16 hours, suggesting their potential as therapeutic agents against the virus.
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Thanks to recent advances in random amplification technologies, metagenomic surveillance expanded the number of novel, often unclassified viruses within the family Rhabdoviridae. Using a vector-enabled metagenomic (VEM) tool, we identified a novel rhabdovirus in Aedes cantans mosquitoes collected from Germany provisionally named Ohlsdorf virus (OHSDV). The OHSDV genome encodes the canonical rhabdovirus structural proteins (N, P, M, G and L) with alternative ORF in the P gene.

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  • - Mayaro virus (MAYV) is an arthropod-borne virus linked to prolonged joint pain, and currently, there are no effective antiviral drugs or vaccines available for its treatment.
  • - Researchers evaluated seven new thieno[2,3-b]pyridine derivatives, finding they could effectively reduce MAYV viral production in non-toxic concentrations in cell cultures.
  • - One promising derivative not only inhibited MAYV early in the replication process but also impacted the virus's later stages, indicating its potential as an antiviral treatment for alphaviruses, though further in vivo studies are needed.
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  • Research on dolabellane diterpenes from brown algae indicates strong anti-HIV-1 activity, but similar studies on those from octocorals are lacking.
  • Two dolabellane compounds were isolated from the Caribbean octocoral Eunicea laciniata, showing low anti-HIV-1 activity and toxicity.
  • Derivatives of the main dolabellane were created and demonstrated a 100-fold increase in anti-HIV-1 potency, particularly compounds 3 and 5, suggesting they are promising antiviral agents regardless of their ring junction configuration.
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Article Synopsis
  • - The marine alga Dictyota pfaffii from Northeast Brazil produces dolabellane diterpenes, which could be developed into antiviral drugs targeting HIV-1 by inhibiting reverse transcriptase (RT).
  • - Researchers discovered three new diterpenes, dolabelladienols A-C, and confirmed their structures using techniques like NMR and X-ray diffraction.
  • - Compounds 1 and 2 showed strong anti-HIV-1 activity (IC50 = 2.9 and 4.1 μM) with low toxicity to tumor cells, suggesting they are promising candidates for anti-HIV therapies.
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The emergence of a multidrug-resistant HIV-1 strain and the toxicity of anti-HIV-1 compounds approved for clinical use are the most significant problems facing antiretroviral therapies. Therefore, it is crucial to find new agents to overcome these issues. In this study, we synthesized a series of new oxoquinoline acyclonucleoside phosphonate analogues (ethyl 1-[(diisopropoxyphosphoryl)methyl]-4-oxo-1,4-dihydroquinoline-3-carboxylates 3a-3k), which contained different substituents at the C6 or C7 positions of the oxoquinoline nucleus and an N1-bonded phosphonate group.

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In the present article, we describe the synthesis, anti-HIV1 profile and molecular modeling evaluation of 11 oxoquinoline derivatives. The structure-activity relationship analysis revealed some stereoelectronic properties such as LUMO energy, dipole moment, number of rotatable bonds, and of hydrogen bond donors and acceptors correlated with the potency of compounds. We also describe the importance of substituents R(2) and R(3) for their biological activity.

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The synthetic n-alkyl esters of gallic acid (GA), also known as gallates, especially propyl, octyl and dodecyl gallates, are widely employed as antioxidants by food and pharmaceutical industries. The inhibitory effects of GA and 15 gallates on Herpes Simplex Virus type 1 (HSV-1) and Human Immunodeficiency Virus (HIV-1) replication were investigated here. After a preliminary screening of these compounds, GA and pentyl gallate (PG) seemed to be the most active compounds against HSV-1 replication and their mode of action was characterized through a set of assays, which attempted to localize the step of the viral multiplication cycle where impairment occurred.

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We describe in this paper that the chloroxoquinolinic ribonucleoside 6-chloro-1,4-dihydro-4-oxo-1-(beta-D-ribofuranosyl)-quinoline-3-carboxylic acid (compound A) inhibits the HIV-1 replication in human primary cells. We initially observed that compound A inhibited HIV-1 infection in peripheral blood mononuclear cells (PBMCs) in a dose-dependent manner, resulting in an EC(50) of 1.5 +/- 0.

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We recently described that a dollabelane diterpene isolated from the marine algae Dictyota pfaffii (Dolabelladienetriol) inhibits the human immunodeficiency virus type 1 (HIV-1) enzyme reverse transcriptase (RT), and HIV-1 replication in primary cells. Based on these findings, we investigated additional antiretroviral properties of Dolabelladienetriol. Here, we describe that Dolabelladienetriol blocked the synthesis and integration of HIV-1 provirus and completely abrogated viral replication in primary cells.

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We describe in this paper that the dolabellane diterpene 8,10,18-trihydroxy-2,6-dolabelladiene (3), isolated from the marine algae Dictyota pfaffii, inhibits the HIV-1 infection in human primary cells and tumor cell lines. We initially observed that compound 3 inhibited the activity of a purified HIV-1 enzyme reverse transcriptase (RT) in a dose-dependent manner, with an IC (50) value of 16.5 +/- 4.

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The Iboga alkaloid congener 18-methoxycoronaridine (18-MC) exhibits in vitro leishmanicidal and in vivo anti-addiction properties. In this paper, we describe that 18-MC inhibits HIV-1 infection in human peripheral blood mononuclear cells (PBMCs) and monocyte-derived macrophages. We found that 18-MC inhibits the replication of primary isolates of HIV-1 in a dose-dependent manner, regardless of the preferential chemokine receptor usage of the isolates, at non-cell-toxic concentrations.

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