Non-Toxic Virucidal Macromolecules Show High Efficacy Against Influenza Virus Ex Vivo and In Vivo.
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ABSTRACT:
SUBMITTER: Kocabiyik O
PROVIDER: S-EPMC7856883 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundHand washing is an important targeted hygiene intervention for limiting the spread of infectious agents, including the Ebola virus, which continues to re-emerge. We have assessed the virucidal efficacy of a commercially available liquid hand wash product (LHW) for inactivating Ebola virus.MethodsThe ASTM E1052-11 Standard was used to evaluate the efficacy of an LHW containing the microbicidal active salicylic acid for inactivating Ebola virus - Makona variant suspended in an organic load. Three concentrations (12.5%, 25%, 50%) of three lots of LHW prepared in 440 ppm hard water were evaluated at room temperature for 20, 30, and 60 s contact time.ResultsA 25% solution of the LHW caused 4.5 log10 and 4.8 log10 reduction in Ebola virus titer within 20 and 30 s, respectively. The efficacy of a 12.5% LHW solution was lower (1.9 and 2.0 log10 reduction in titer within 20 and 30 s, respectively). The efficacy of the 50% LHW solution could not be measured, due to inability to sufficiently neutralize the LHW at the end of exposure.ConclusionThese results suggest the potential utility of an appropriately formulated liquid hand wash agent during Ebola virus disease outbreaks for use within healthcare, community, and home settings. Such an LHW should also be effective against other enveloped viruses, such as the pandemic coronavirus SARS-CoV-2.
| S-EPMC8336303 | biostudies-literature
Project description:Intracellular delivery of biomolecules, such as proteins and siRNAs, into primary immune cells, especially resting lymphocytes, is a challenge. Here we describe the design and testing of microfluidic intracellular delivery systems that cause temporary membrane disruption by rapid mechanical deformation of human and mouse immune cells. Dextran, antibody and siRNA delivery performance is measured in multiple immune cell types and the approach's potential to engineer cell function is demonstrated in HIV infection studies.
| S-EPMC4395260 | biostudies-literature
Project description:The use of vaccines is the most effective and reliable method for the prevention of viral infections. However, research on evaluation of effective therapeutic agents for use in treatment after infection is necessary. Zanamivir was administered through inhalation for treatment of pandemic influenza A/H1N1 in 2009. However, the emergence of drug-resistant strains can occur rapidly. Alloferon, an immunomodulatory drug developed as an NK cell activator, exerts antiviral effects against various viruses, particularly influenza viruses. Therefore, alloferon and zanamivir were administered in combination in an effort to improve the antiviral effect of zanamivir by reducing H1N1 resistance. First, we confirmed that administration of combined treatment would result in effective inhibition of viral proliferation in MDCK and A549 cells infected with H1N1. Production of IL-6 and MIP-1α in these cells and the activity of p38 MAPK and c-Jun that are increased by H1N1 were inhibited by combined treatment. Mice were then infected intranasally with H1N1, and examination of the antiviral efficacy of the alloferon/zanamivir combination was performed. The results showed that combined treatment after infection with H1N1 prevented weight loss, increased the survival rate, and improved lung fibrosis. Combined treatment also resulted in reduced infiltration of neutrophils and macrophages into the lungs. Combined treatment effectively inhibited the activity of p38 MAPK and c-Jun in lung tissue, which was increased by infection with H1N1. Therefore, the combination of alloferon/zanamivir effectively prevents the development of H1N1-mediated inflammation in the lungs by inhibiting the production of inflammatory mediators and migration of inflammatory cells into lung tissue.
| S-EPMC9820929 | biostudies-literature
Project description:The annual spread of influenza A virus (IAV) infection is a global concern. We examined the IAV-inactivating potential of theaflavin-concentrated tea extract TY-1, which contains abundant polyphenols, including concentrated theaflavins and catechins. TY-1 exhibited concentration- and time-dependent virucidal activity against IAV. Specifically, 5.0 mg/mL TY-1 induced a 1.33 and ≥ 5.17 log10 50% tissue culture infective dose/mL reduction of the viral titer compared with dextrin as the diluent control within 30 min and 6 h reaction time, respectively. The high virucidal activity of TY-1 was attributed to the combined additive activities of multiple virucidal components, including theaflavins, which led to an investigation of the virucidal mechanism of action of TY-1. Western blotting revealed that TY-1 treatment reduced the band intensity of hemagglutinin and induced the appearance of additional high molecular mass bands/ladders. In addition, TY-1 treatment also reduced the band intensity of neuraminidase (NA). A hemagglutination assay revealed that TY-1 reduced hemagglutination activity, and an NA assay revealed reduced NA activity. These results indicated that TY-1 caused structural abnormalities in IAV spike proteins, possibly leading to their destruction. Reverse transcription polymerase chain reaction (PCR) targeting the IAV genome and electron microscopic observation of viral particles revealed that upon application of TY-1, the PCR products dissipated, which indicates that TY-1 destroyed the IAV genome, and the number of viral particles reduced. Overall, TY-1 exhibited multiple modes of IAV-inactivating activity. Our findings support the possible future practical use of TY-1 as a virucidal supplemental agent that can contribute to IAV infection control.
| S-EPMC8456404 | biostudies-literature
Project description:The defense against influenza virus (IV) infections still poses a series of challenges. The current antiviral arsenal against influenza viruses is in fact limited; therefore, the development of new anti-influenza strategies effective against antigenically different viruses is an urgent priority. Bioactive compounds derived from medicinal plants and fruits may provide a natural source of candidates for such broad-spectrum antivirals. In this regard, cranberry (Vaccinium macrocarpon Aiton) extracts on the basis of their recognized anti-adhesive activities against bacteria, may provide potential compounds able to prevent viral attachment to target cells. Nevertheless, only few studies have so far investigated the possible use of cranberry extracts as an antiviral tool. This study focuses on the suitability of a cranberry extract as a direct-acting anti-influenza compound. We show that the novel cranberry extract Oximacro® inhibits influenza A and B viruses (IAV, IBV) replication in vitro because of its high content of A-type proanthocyanidins (PAC-A) dimers and trimers. Mechanistic studies revealed that Oximacro® prevents attachment and entry of IAV and IBV into target cells and exerts a virucidal activity. Oximacro® was observed to interact with the ectodomain of viral hemagglutinin (HA) glycoprotein, thus suggesting the interference with HA functions and a consequent loss of infectivity of IV particles. Fluorescence spectroscopy revealed a reduction in the intrinsic fluorescence of HA protein after incubation with purified dimeric PAC-A (PAC-A2), thus confirming a direct interaction between HA and Oximacro® PAC-A2. In silico docking simulations further supported the in vitro results and indicated that among the different components of the Oximacro® chemical profile, PAC-A2 exhibited the best binding propensity with an affinity below 10 nM. The role of PAC-A2 in the anti-IV activity of Oximacro® was eventually confirmed by the observation that it prevented IAV and IVB replication and caused the loss of infectivity of IV particles, thus indicating PAC-A2 as the major active component of Oximacro®. As a whole, these results suggest Oximacro® as a potential candidate to create novel antiviral agents of natural origin for the prevention of IV infections.
| S-EPMC6090095 | biostudies-literature
Project description:Recent advances in class II tetramer staining technology have allowed reliable direct ex vivo visualization of antigen-specific CD4 T cells. In order to define the frequency and phenotype of a prototype response to a nonpersistent pathogen, we have used such techniques to analyze influenza virus-specific memory CD4 T cells directly from blood. These responses are stably detectable ex vivo at low frequencies (range, 0.00012 to 0.0061% of CD4 T cells) and display a distinct "central memory" CD62L(+) phenotype.
| S-EPMC421690 | biostudies-other
Project description:Influenza A(H1N1)pdm virus caused the first human pandemic of the 21st century. Although various probiotic Lactobacillus species have been shown to have anti-microbial effects against pneumonia-inducing pathogens, the prophylactic efficacy and mechanisms behind their protection remain largely unknown. Here, we evaluated the prophylactic efficacy of heat-killed Lactobacillus pentosus b240 against lethal influenza A(H1N1)pdm virus infection in a mouse model. To further define the protective responses induced by b240, we performed virologic, histopathologic, and transcriptomic analyses on the mouse lungs. Although we did not observe an appreciable effect of b240 on virus growth, cytokine production, or histopathology, gene expressional analysis revealed that oral administration of b240 differentially regulates antiviral gene expression in mouse lungs. Our results unveil the possible mechanisms behind the protection mediated by b240 against influenza virus infection and provide new insights into probiotic therapy. Six-week-old female BALB/c mice were used in the study. Oral administration of b240 was initiated in mice at six weeks of age. Mice were orally administered heat-killed Lactobacillus pentosus b240 every day at a dose of 10 mg/mouse in 200 μl of buffered saline for 5 weeks. The control group received saline. To investigate the effects of oral administration of b240 on host immune responses to CA04 virus infection, 9 mice per group were infected with 10 MLD50 of CA04 virus on day 21 post-b240 administration. Three mice per group were euthanized on days 1, 3, and 6 post-infection and their lungs were collected. To investigate the immune responses induced by oral administration of b240 in the lungs of uninfected mice, 15 mice per group were mock-infected with PBS on day 21 post-b240 administration. Three mice per group were euthanized on days 14, 21, 22, 24, and 27 post-b240 administration (-7, 0, 1, 3, and 6 days post-mock infection) and their lungs were collected. These lung tissues were subjected to microarray analysis (three biological replicates per each group).
2013-03-29 | E-GEOD-43764 | biostudies-arrayexpress
Project description:BackgroundVRC01, a potent, broadly neutralizing monoclonal antibody, inhibits simian-HIV infection in animal models. The HVTN 104 study assessed the safety and pharmacokinetics of VRC01 in humans. We extend the clinical evaluation to determine intravenously infused VRC01 distribution and protective function at mucosal sites of HIV-1 entry.MethodsHealthy, HIV-1-uninfected men (n = 7) and women (n = 5) receiving VRC01 every 2 months provided mucosal and serum samples once, 4-13 days after infusion. Eleven male and 8 female HIV-seronegative volunteers provided untreated control samples. VRC01 levels were measured in serum, secretions, and tissue, and HIV-1 inhibition was determined in tissue explants.ResultsMedian VRC01 levels were quantifiable in serum (96.2 μg/mL or 1.3 pg/ng protein), rectal tissue (0.11 pg/ng protein), rectal secretions (0.13 pg/ng protein), vaginal tissue (0.1 pg/ng protein), and cervical secretions (0.44 pg/ng protein) from all recipients. VRC01/IgG ratios in male serum correlated with those in paired rectal tissue (r = 0.893, P = 0.012) and rectal secretions (r = 0.9643, P = 0.003). Ex vivo HIV-1Bal26 challenge infected 4 of 21 rectal explants from VRC01 recipients versus 20 of 22 from controls (P = 0.005); HIV-1Du422.1 infected 20 of 21 rectal explants from VRC01 recipients and 12 of 12 from controls (P = 0.639). HIV-1Bal26 infected 0 of 14 vaginal explants of VRC01 recipients compared with 23 of 28 control explants (P = 0.003).ConclusionIntravenous VRC01 distributes into the female genital and male rectal mucosa and retains anti-HIV-1 functionality, inhibiting a highly neutralization-sensitive but not a highly resistant HIV-1 strain in mucosal tissue. These findings lend insight into VRC01 mucosal infiltration and provide perspective on in vivo protective efficacy.FundingNational Institute of Allergy and Infectious Diseases and Bill & Melinda Gates Foundation.
| S-EPMC8363291 | biostudies-literature
Project description:Oral delivery of macromolecules requires permeation enhancers (PEs) adaptable to formulation. Sucrose laurate (SL) (D1216), a food grade surfactant, was assessed in Caco-2 monolayers, isolated rat intestinal tissue mucosae, and rat intestinal instillations. Accordingly, 1 mM SL increased the apparent permeability coefficient (Papp) of [14C]-mannitol and reduced transepithelial electrical resistance (TEER) across monolayers. It altered expression of the tight junction protein, ZO-1, increased plasma membrane potential, and decreased mitochondrial membrane potential in Caco-2 cells. The concentrations that increased flux were of the same order as those that induced cytotoxicity. In rat colonic tissue mucosae, the same patterns emerged in respect to the concentration-dependent increases in paracellular marker fluxes and TEER reductions with 5 mM being the key concentration. While the histology revealed some perturbation, ion transport capacity was retained. In rat jejunal and colonic instillations, 50 and 100 mM SL co-administered with insulin induced blood glucose reductions and achieved relative bioavailability values of 2.4% and 8.9%, respectively, on a par with the gold standard PE, sodium caprate (C10). The histology of the intestinal loops revealed little damage. In conclusion, SL is a candidate PE with high potential for emulsion-based systems. The primary action is plasma membrane perturbation, leading to tight junction openings and a predominant paracellular flux.
| S-EPMC6921008 | biostudies-literature
Project description:Human noroviruses are the major cause of non-bacterial acute gastroenteritis worldwide. Since no therapeutic agent has been proven to prevent human norovirus infection yet, preventive healthcare interventions to block the infection routes play an important role in infection control. One of the possible infection routes of human noroviruses are through contaminated hands, but no hand antiseptics have been proven effective. Olanexidine gluconate is a new biguanide compound that has already been approved for sale as an antiseptic for the surgical field in Japan. A new hand antiseptic was developed using olanexidine gluconate in this study, and its virucidal efficacy against human noroviruses was evaluated using modified RT-qPCR that can account for genome derived from intact viruses using RNase A and photo-reactive intercalators. We tested the virucidal efficacy of five materials; two olanexidine gluconate antiseptics (hand rub formulation and surgical field formulation), two kinds of ethanol solutions at different pH (approx. 3 or 7), and a base component of olanexidine gluconate hand rub formulation against 11 human norovirus genotypes by culture-independent methods. The infectivity of murine norovirus (MNV), a surrogate for human norovirus, was significantly reduced after use of the antiseptics. The olanexidine gluconate hand rub demonstrated the strongest virucidal efficacy against human norovirus among the five tested materials. This study showed that olanexidine gluconate has the potential to become a strong tool for the prevention of human norovirus infection.
| S-EPMC7225205 | biostudies-literature