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Water-Soluble Fullerene C₆₀ Derivatives Are Effective Inhibitors of Influenza Virus Replication.

ABSTRACT: The influenza virus genome features a very high mutation rate leading to the rapid selection of drug-resistant strains. Due to the emergence of drug-resistant strains, there is a need for the further development of new potent antivirals against influenza with a broad activity spectrum. Thus, the search for a novel, effective broad-spectrum antiviral agent is a top priority of medical science and healthcare systems. In this paper, derivatives based on fullerenes with broad virus inhibiting activities in vitro against a panel of influenza viruses were described. The antiviral properties of water-soluble fullerene derivatives were studied. It was demonstrated that the library of compounds based on fullerenes has cytoprotective activity. Maximum virus-inhibiting activity and minimum toxicity were found with compound 2, containing residues of salts of 2-amino-3-cyclopropylpropanoic acid (CC₅₀ > 300 µg/mL, IC₅₀ = 4.73 µg/mL, SI = 64). This study represents the initial stage in a study of fullerenes as anti-influenza drugs. The results of the study lead us conclude that five leading compounds (1-5) have pharmacological prospects.

SUBMITTER: Sinegubova EO

PROVIDER: S-EPMC10053623 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Water-Soluble Fullerene C<sub>60</sub> Derivatives Are Effective Inhibitors of Influenza Virus Replication.

Sinegubova Ekaterina O EO Kraevaya Olga A OA Volobueva Aleksandrina S AS Zhilenkov Alexander V AV Shestakov Alexander F AF Baykov Sergey V SV Troshin Pavel A PA Zarubaev Vladimir V VV Zarubaev Vladimir V VV

Microorganisms 20230307 3

The influenza virus genome features a very high mutation rate leading to the rapid selection of drug-resistant strains. Due to the emergence of drug-resistant strains, there is a need for the further development of new potent antivirals against influenza with a broad activity spectrum. Thus, the search for a novel, effective broad-spectrum antiviral agent is a top priority of medical science and healthcare systems. In this paper, derivatives based on fullerenes with broad virus inhibiting activi ...[more]

PMID: 36985255

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Project description:A new class of water-soluble C60 transfecting agents has been prepared using Hirsch-Bingel chemistry and assessed for their ability to act as gene-delivery vectors in vitro. In an effort to elucidate the relationship between the hydrophobicity of the fullerene core, the hydrophilicity of the water-solubilizing groups, and the overall charge state of the C60 vectors in gene delivery and expression, several different C60 derivatives were synthesized to yield either positively charged, negatively charged, or neutral chemical functionalities under physiological conditions. These fullerene derivatives were then tested for their ability to transfect cells grown in culture with DNA carrying the green fluorescent protein (GFP) reporter gene. Statistically significant expression of GFP was observed for all forms of the C60 derivatives when used as DNA vectors and compared to the ability of naked DNA alone to transfect cells. However, efficient in vitro transfection was only achieved with the two positively charged C60 derivatives, namely, an octa-amino derivatized C60 and a dodeca-amino derivatized C60 vector. All C60 vectors showed an increase in toxicity in a dose-dependent manner. Increased levels of cellular toxicity were observed for positively charged C60 vectors relative to the negatively charged and neutral vectors. Structural analyses using dynamic light scattering and optical microscopy offered further insights into possible correlations between the various derivatized C60 compounds, the C60 vector/DNA complexes, their physical attributes (aggregation, charge) and their transfection efficiencies. Recently, similar Gd@C60-based compounds have demonstrated potential as advanced contrast agents for magnetic resonance imaging (MRI). Thus, the successful demonstration of intracellular DNA uptake, intracellular transport, and gene expression from DNA using C60 vectors suggests the possibility of developing analogous Gd@C60-based vectors to serve simultaneously as both therapeutic and diagnostic agents.

Project description:The human body contains 60-70% water, depending on age. As a body fluid, it is not only a medium in which physical and chemical processes take place, but it is also one of the active mediators. Water is the richest substance with non-covalent hydrogen bonds. Water molecules, by themselves (in vacuum), are diamagnetic but when organized into clusters, they become diamagnetic or paramagnetic. Also, biomolecules (DNA, collagen, clathrin, and other proteins) have non-covalent hydrogen bonds in their structure. The interaction, as well as signal transmission, between water and biomolecules is achieved through the vibrations of covalent and non-covalent hydrogen bonds, which determine the state and dynamics of conformational changes in biomolecules. Disruptive conformational changes in biomolecules, cells, and tissues lead to their dysfunctionality, so they are a frequent cause of many disorders and diseases. For example, the rearrangement of hydrogen bonding due to mitochondrial disease mutation in cytochrome bc1 disturbs heme bH redox potential and spin state. In order to prevent and repair the dysfunctional conformational changes, a liquid substance was developed based on the second derivative of the C60 molecule (SD-C60), which has classical and quantum properties. The characterization of SD-C60 by UV-VIS-NIR, FTIR, TEM, and AFM/MFM was performed and it is shown that SD-C60 water layers generate vibrations with near-zero phase dispersion which are transmitted through Fibonacci's water chains to biomolecules. In comparison with previously published SD-C60 derivate (3HFWC, size until 10 nm, and 1-5 water layers), the improved formulation (3HFWC-W, size 10-25 nm, and 6-9 water layers) showed multiplied cytotoxic activity against melanoma cell lines of different aggressiveness. Apart from this, the mode of action was preserved and based on an induction of senescence rather than cell death. Importantly, high selectivity towards malignant phenotypes was detected. Observed effects can be ascribed to a machinery of hydrogen bonds, which are generated in SD-C60 and transmitted through water to biomolecules. This approach may open a new field in science and healthcare-a "water-based nanomedicine".

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Water-Soluble Fullerene C₆₀ Derivatives Are Effective Inhibitors of Influenza Virus Replication.

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Water-Soluble Fullerene C<sub>60</sub> Derivatives Are Effective Inhibitors of Influenza Virus Replication.

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Water-Soluble Fullerene C60 Derivatives Are Effective Inhibitors of Influenza Virus Replication.

Publications

Water-Soluble Fullerene C<sub>60</sub> Derivatives Are Effective Inhibitors of Influenza Virus Replication.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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Water-Soluble Fullerene C₆₀ Derivatives Are Effective Inhibitors of Influenza Virus Replication.