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Electron microscopy of SIV treated under permeabilizing conditions revealed holes in the membrane of the virus. SIV samples that were untreated (A and D), treated under nonpermeabilizing conditions (B and E), or treated under permeabilizing conditions (C and F to I) were examined by transmission electron microscopy. Panels G and I are larger magnifications of the images in panels F and H, respectively. Magnifications: ϫ 4,000 (A), ϫ 20,000 (B to F and H), and ϫ 40,000 (G and I).
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Recent evidence suggests that human immunodeficiency virus type 1 (HIV-1) particles assemble and bud selectively through areas in the plasma membrane of cells that are highly enriched with glycosylphosphatidylinositol-anchored proteins and cholesterol, called lipid rafts. Since cholesterol is required to maintain lipid raft structure and function,...
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Citations
... Cyclodextrins (CDs) are sugar polymers structurally similar to native mucin glycoproteins and are compatible with nasal epithelial cells [11]. Known to interact and sequester viral membrane cholesterol, cyclodextrins have demonstrated antiviral properties against enveloped viruses by disrupting lipid rafts and cell cholesterol depletion [12][13][14]. This study describes the screening and characterization of the antiviral effects of various types of cyclodextrins to prevent and reduce the severity of mucocutaneous viral infection. ...
The emergence and mutation of pathogenic viruses have been occurring at an unprecedented rate in recent decades. The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed into a global public health crisis due to extensive viral transmission. In situ RNA mapping has revealed angiotensin-converting enzyme 2 (ACE2) expression to be highest in the nose and lower in the lung, pointing to nasal susceptibility as a predominant route for infection and the cause of subsequent pulmonary effects. By blocking viral attachment and entry at the nasal airway using a cyclodextrin-based formulation, a preventative therapy can be developed to reduce viral infection at the site of entry. Here, we assess the safety and antiviral efficacy of cyclodextrin-based formulations. From these studies, hydroxypropyl beta-cyclodextrin (HPBCD) and hydroxypropyl gamma-cyclodextrin (HPGCD) were then further evaluated for antiviral effects using SARS-CoV-2 pseudotypes. Efficacy findings were confirmed with SARS-CoV-2 Delta variant infection of Calu-3 cells and using a K18-hACE2 murine model. Intranasal pre-treatment with HPBCD-based formulations reduced viral load and inflammatory signaling in the lung. In vitro efficacy studies were further conducted using lentiviruses, murine hepatitis virus (MHV), and influenza A virus subtype H1N1. These findings suggest HPBCD may be used as an agnostic barrier against transmissible pathogens, including but not limited to SARS-CoV-2.
... The Gag proteins of several retroviruses, including HIV-1 (16,17,(28)(29)(30)(31)(32)(33), MLV (34), and HTLV-1 (35), have been shown to associate with detergent-resistant membranes, which serve as a biochemical surrogate for raft association. Depletion of cellular cholesterol impairs HIV-1 assembly by inhibiting the association of Gag with the PM (17,36), and removing cholesterol from the viral envelope disrupts HIV-1 particle infectivity (37)(38)(39). Together, these results indicate that the specialized lipid composition of the PM at viral assembly sites, and the raft-like properties of the viral envelope, play a critical role in the replication of HIV-1 and perhaps other retroviruses. However, the relationship between lipid composition and retroviral assembly, release, and maturation remains poorly understood. ...
... Previous studies have demonstrated that depletion of cholesterol or increasing levels of ceramide in target cells has a significant impact on HIV-1 infectivity (39,45,(56)(57)(58)(59), suggesting that raft-like microdomains in the PM function in promoting HIV-1 infection. To investigate whether inhibiting nSMase2 activity in target cells has an effect on HIV-1 infectivity, we treated TZM-bl target cells with a dose escalation of PDDC and then infected with WT HIV-1. ...
HIV-1 assembly occurs at the inner leaflet of the plasma membrane (PM) in highly ordered membrane microdomains. The size and stability of membrane microdomains is regulated by activity of the sphingomyelin hydrolase neutral sphingomyelinase 2 (nSMase2) that is localized primarily to the inner leaflet of the PM. In this study, we demonstrate that pharmacological inhibition or depletion of nSMase2 in HIV-1-producer cells results in a block in the processing of the major viral structural polyprotein Gag and the production of morphologically aberrant, immature HIV-1 particles with severely impaired infectivity. We find that disruption of nSMase2 also severely inhibits the maturation and infectivity of other primate lentiviruses HIV-2 and simian immunodeficiency virus, has a modest or no effect on nonprimate lentiviruses equine infectious anemia virus and feline immunodeficiency virus, and has no effect on the gammaretrovirus murine leukemia virus. These studies demonstrate a key role for nSMase2 in HIV-1 particle morphogenesis and maturation.
... HPbCD prevents HIV-1 and SIV infection of target cells in vitro at both at the cellular and viral level. Whereas HPbCD extracts cholesterol from plasma membrane lipid rafts which are necessary for HIV entry and egress (42,43), HPbCD also depletes cholesterol from viral envelopes, leading to viral inactivation (44,45). In vivo, however, the role of HPbCD in reducing viral infection and replication is less clear. ...
SIV infection of nonhuman primates is the principal model system for assessing HIV disease progression and therapeutic development. HPβCD has recently been incorporated as a solubilizing agent in coformulations of ARVs in SIV-infected nonhuman primates.
... Более того, еще одним вариантом может стать наличие хелаторов холестерина. Установлена также эффективность снижения инфекционности других вирусов, действующих на вирусную мембрану [46]. Ингибирующая активность, обусловленная синергетическим действием веществ, была выявлена при различных комбинациях воздействия экстрактом бузины. ...
Anthocyanins and polyphenols are the main biologically active substances in elderberry. Extraction methods exert a significant effect on the extraction effectiveness, bioavailability and preservation of biologically active compounds. The aim of this work was a review of the published results of scientific studies of elderberry and products of its processing, their effect on the body, as well as examination of methods for extraction and encapsulation of biologically active substances of elderberry. The review includes papers in English and Russian. A search for foreign literature in English on this theme was carried out in the bibliographic databases Google Scholar, Scopus, Web of Science, Elsevier, ResearchGate. To select scientific papers in Russian, a search was done in the scientific electronic library eLIBRARY.RU by keywords. The review of the scientific publications shows that the results of numerous studies confirm the high antioxidant activity of elderberry (Sambucus nigra L.), as well as wild elderberry (Sambucus ebulus), growing on the territory of the Belarus Republic and in other countries of Europe, Asia, North Africa and North America. This plant is applied in the traditional medicine and is used in the food industry as raw materials for creation of prophylactic and functional products due to the presence in the chemical composition of elderberry (Sambucus nigra L.) of bioactive flavonoids such as quercetin, kempherol and rutin, and other phenolic compounds. Bioactive compounds of elderberry possess several unique biological and pharmacological properties including the antioxidant, anti-tumor, anti-depressive, anti-diabetic, antiviral and antibacterial activities. To extract bioactive substances from elderberry, traditional extraction methods are used, such as maceration and Soxhlet extraction, as well as modern promising “green” technologies (for example, supercritical fluids, pulsed electric field, emulsion liquid extraction, microwave-assisted and ultrasound-assisted extraction). To preserve and protect biologically active substances in elderberry, encapsulation methods that are most effective are employed. The materials of this paper can be used in future studies on optimization of extraction processes to increase the nutritional value and antioxidant activity of new functional foods, food additives and products of pharmaceutical industry.
... Additionally, due to a wide range of binding motifs, pillararenes offer the potential to interact directly with viruses and inhibit infection, for instance, it was reported for human papillomavirus [119]. To date, the use of other macrocycles as antivirals is also limited by few examples [120,121], including a recent report on the inhibition of a large variety of viruses, including herpes simplex virus 2 (HSV-2), respiratory syncytial virus (RSV), and SARS-CoV-2, by cucurbit[n]urils via host-guest supramolecular interactions between viral surface proteins and the cavity of cucurbit[n]urils [122]. ...
Since their discovery in 2008 by N. Ogoshi and co-authors, pillararenes (PAs) have become popular hosts for molecular recognition and supramolecular chemistry, as well as other practical applications. The most useful property of these fascinating macrocycles is their ability to accommodate reversibly guest molecules of various kinds, including drugs or drug-like molecules, in their highly ordered rigid cavity. The last two features of pillararenes are widely used in various pillararene-based molecular devices and machines, stimuli-responsive supramolecular/host–guest systems, porous/nonporous materials, organic–inorganic hybrid systems, catalysis, and, finally, drug delivery systems. In this review, the most representative and important results on using pillararenes for drug delivery systems for the last decade are presented.
... La infectividad del virus de influenza (7) , del virus del moquillo canino (8) y del virus de la hepatitis B (VHB) (9) es sensible al agotamiento de colesterol de la membrana viral, mientras que, el virus de la leucemia murina (10) , del Ébola y del virus Marburg (11) son sensibles al agotamiento del colesterol de la membrana celular del huésped. El colesterol de las membranas se requiere para la infección por el virus de la inmunodeficiencia humana (VIH) (12,13) , el virus de la gastroenteritis (14,15) , el virus de la enfermedad de Borna (16) y los Herpesvirus (17)(18)(19)(20) ; mientras que, la infección por el virus de la estomatitis vesicular, demostró ser independiente del agotamiento del colesterol celular y viral (8,21) . Con respecto al DENV, los resultados sobre la función del colesterol celular para la infección son controvertidos. ...
El dengue es la arbovirosis con mayor incidencia a nivel mundial. Aproximadamente 100 millones de casos de dengue con signos de alarma y entre 250.000 y 500.000 casos de dengue grave, se registran anualmente. En Ecuador, en los últimos cuatro años se han registrado 83.472 casos de dengue. Estudios previos evidencian un incremento de los casos que cursan con disfunción hepática. El objetivo de este estudio fue analizar la asociación entre los niveles séricos de las enzimas aspartato aminotransferasa y alanino aminotransferasa y el perfil lipídico en pacientes con infección confirmada de Dengue. Se estudiaron 110 pacientes seleccionados sin distingo de edad, género o procedencia, cuyo diagnóstico fue confirmado virológica y serológicamente. Se incluyó un grupo control seronegativo al virus. En el perfil lipídico se evidenciaron diferencias significativas (p<0,003) en los valores de colesterol total y en infecciones secundarias; mientras que la frecuencia de elevación de ambas aminotransferasas fue alta en pacientes con dengue, no obstante, al comparar cuantitativamente los valores séricos no arrojaron cambios significativos, ni asociación. Se confirma la endemicidad del dengue, los cambios en el perfil lipídico, sin embargo, es evidente la necesidad de estudios poblacionales tomando en cuenta la genética de las poblaciones
... The effect of losing the infectivity of other viruses has been demonstrated, acting on the viral membrane. [108]. The inhibitory activity given by the synergistic action of the substances was demonstrated with various combinations of treatments with EDB extract. ...
Elderberries are appreciated for their antioxidant properties. Sambucus nigra L. is an extremely abundant plant in the wild flora of Romania, but it is underutilized. Elderberry is used in modern and traditional medicine due to the complex chemical composition of the fruit. The content of phenolic compounds is high (516–8974 mg/100 g DW), of which the most abundant are anthocyanins. Phenolic compounds are known for their beneficial effects on the body. Numerous studies have demonstrated the antioxidant capacity, antibacterial, antiviral, antidiabetic, and anticancer properties of the fruit. It is considered that most of the therapeutic properties of elderberries can be correlated with the antioxidant activity they have. S. nigra fruits are also used in the food industry. Some studies have shown that the therapeutic properties of elderberries can also be found in the products obtained from them. Therefore, this review aimed to describe the chemical composition of elderberries and products obtained from them, the positive effects on the body, and the methods by which the bioactive compounds can be extracted from the fruits and analyzed. This manuscript is useful for extraction optimization and characterization in order to valorize new functional foods, food supplements, and also in new pharmaceutical products.
... 20,21 Additionally, due to their wide range of binding motifs, macrocycles offer the potential to interact directly with viruses and inhibit infection. However, to date, the use of macrocycles as antivirals has been limited to modified macrocycles 22 or via indirect effects (for example, via binding cholesterol 23 ). Cucurbit[n]urils (CB[n]s) are barrel-shaped macrocycles composed of "n" glycoluril monomers/units linked by methylene bridges 24 that are produced in a range of ring sizes, which can then be separated into discrete sizes from n = 5−8 to 10. 25−27 Like other macrocycles, CB[n]s have a cavity capable of supramolecular binding to a range of guest molecules 28 with the larger CBs (CB [8] and CB [10]) capable of including two guests simultaneously. ...
Viruses are microscopic pathogens capable of causing disease and are responsible for a range of human mortalities and morbidities worldwide. They can be rendered harmless or destroyed with a range of antiviral chemical compounds. Cucurbit[n]urils (CB[n]s) are a family of macrocycle chemical compounds existing as a range of homologues; due to their structure, they can bind to biological materials, acting as supramolecular "hosts" to "guests", such as amino acids. Due to the increasing need for a nontoxic antiviral compound, we investigated whether cucurbit[n]urils could act in an antiviral manner. We have found that certain cucurbit[n]uril homologues do indeed have an antiviral effect against a range of viruses, including herpes simplex virus 2 (HSV-2), respiratory syncytial virus (RSV) and SARS-CoV-2. In particular, we demonstrate that CB[7] is the active homologue of CB[n], having an antiviral effect against enveloped and nonenveloped species. High levels of efficacy were observed with 5 min contact times across different viruses. We also demonstrate that CB[7] acts with an extracellular virucidal mode of action via host-guest supramolecular interactions between viral surface proteins and the CB[n] cavity, rather than via cell internalization or a virustatic mechanism. This finding demonstrates that CB[7] acts as a supramolecular virucidal antiviral (a mechanism distinct from other current extracellular antivirals), demonstrating the potential of supramolecular interactions for future antiviral disinfectants.
... The most frequently reported CDs and CD derivative mechanisms of action include the virucidal activity and the inhibition of the early steps of virus replication. Notably, the virucidal activity was associated with the ability of CD to complex the cholesterol molecules of the host cell membrane or the viral lipid envelope, respectively, rendering the cell less susceptible to viral infections or causing a direct impairment of the viral particle [24][25][26][27][28][29][30]. Alternatively, Jones et al. recently reported the strong virucidal activity of CDs modified with mercaptoundecane sulfonic acids due to their mimicking action of key cellular receptors [31]. ...
Cyclodextrins and cyclodextrin derivatives were demonstrated to improve the antiviral potency of numerous drugs, but also to be endowed with intrinsic antiviral action. They are suitable building blocks for the synthesis of functionalized polymer structures with potential antiviral activity. Accordingly, four water-soluble hyper-branched beta cyclodextrin (βCD)-based anionic polymers were screened against herpes simplex virus (HSV-2), respiratory syncytial virus (RSV), rotavirus (HRoV), and influenza virus (FluVA). They were characterized by FTIR-ATR, TGA, elemental analyses, zeta-potential measurements, and potentiometric titrations, while the antiviral activity was investigated with specific in vitro assays. The polymer with the highest negative charge, pyromellitic dianhydride-linked polymer (P_PMDA), showed significant antiviral action against RSV and HSV-2, by inactivating RSV free particles and by altering HSV-2 binding to the cell. The polymer fraction with the highest molecular weight showed the strongest antiviral activity and both P_PMDA and its active fractions were not toxic for cells. Our results suggest that the polymer virucidal activity against RSV can be exploited to produce new antiviral materials to counteract the virus dissemination through the air or direct contact. Additionally, the strong HSV-2 binding inhibition along with the water solubility of P_PMDA and the acyclovir complexation potential of βCD are attractive features for developing new therapeutic topical options against genital HSV-2 infection.
... Lipid rafts are plasma membrane subdomains containing a high amount of cholesterol (Hooper 1999;Liao et al. 2001;Graham et al. 2003;Liao et al. 2003). They exist as distinct liquid-ordered membrane regions that are resistant to extraction with nonionic detergents. ...
... Previous reports showed that lipid components, such as cholesterol, sphingolipid, and phosphatidylinositol-4,5bisphosphate, play important roles in HIV-1 infection (Hooper 1999;Liao et al. 2001;Graham et al. 2003;Liao et al. 2003;Hogue et al. 2011;Kempf et al. 2015). Changes in the quantities or distributions of these lipids can lead to reduced entry, assembly, or release of virus, which delays viral replication Waheed et al. 2009;Mariani et al. 2014). ...
... Changes in the quantities or distributions of these lipids can lead to reduced entry, assembly, or release of virus, which delays viral replication Waheed et al. 2009;Mariani et al. 2014). Among these lipid components, cholesterol is most important for the maintenance of lipid raft formation and integrity (Kabouridis et al. 2000;Graham et al. 2003;Ivankin et al. 2012). The present study mainly focused on the role of GAL3 on cholesterol levels. ...
Galectin-3 (GAL3) is a β-galactoside-binding lectin expressed in CD4 T cells infected with human immunodeficiency virus-1 (HIV-1). GAL3 promotes HIV-1 budding by associating with ALIX and Gag p6. GAL3 has been shown to localize in membrane lipid rafts in dendritic cells and positively regulate cell migration. HIV-1 spreads between T cells by forming supramolecular structures (virological synapses [VSs]), whose integrity depends on lipid rafts. Here, we addressed the potential role of GAL3 in cell-to-cell transmission of HIV-1 in CD4 T cells. GAL3 expressed in donor cells was more important for facilitating HIV-1 cell-to-cell transfer than GAL3 expressed in target cells. GAL3 was found to be co-transferred with Gag from HIV-1-positive donor to HIV-1-negative target T cells. HIV-1 infection induced translocation of GAL3 together with Gag to the cell–cell interfaces and colocalize with GM1, where GAL3 facilitated VS formation. GAL3 regulated the coordinated transfer of Gag and flotillin-1 into plasma membrane fractions. Finally, depletion of GAL3 reduced the cholesterol levels in membrane lipid rafts in CD4 T cells. These findings provide evidence that endogenous GAL3 stimulates lipid raft components and facilitates intercellular HIV-1 transfer among CD4 T cells, offering another pathway by which GAL3 regulates HIV-1 infection. These findings may inform the treatment of HIV-1 infection based on targeting GAL3 to modulate lipid rafts.
