scholarly journals Metabolites of Seaweeds as Potential Agents for the Prevention and Therapy of Influenza Infection

Marine Drugs ◽  
2019 ◽  
Vol 17 (6) ◽  
pp. 373 ◽  
Author(s):  
Natalia Besednova ◽  
Tatiana Zaporozhets ◽  
Tatiana Kuznetsova ◽  
Ilona Makarenkova ◽  
Lydmila Fedyanina ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Broad Spectrum ◽  
Influenza Infection ◽  
Biologically Active ◽  
New Drugs ◽  
New Therapeutic Approaches ◽  
Or Genes ◽  
Prevention And Therapy

Context: Seaweed metabolites (fucoidans, carrageenans, ulvans, lectins, and polyphenols) are biologically active compounds that target proteins or genes of the influenza virus and host components that are necessary for replication and reproduction of the virus. Objective: This review gathers the information available in the literature regarding to the useful properties of seaweeds metabolites as potential agents for the prevention and therapy of influenza infection. Materials and methods: The sources of scientific literature were found in various electronic databases (i.e., PubMed, Web of Science, and ScienceDirect) and library search. The retrospective search depth is 25 years. Results: Influenza is a serious medical and social problem for humanity. Recently developed drugs are quite effective against currently circulating influenza virus strains, but their use can lead to the selection of resistant viral strains. In this regard, new therapeutic approaches and drugs with a broad spectrum of activity are needed. Metabolites of seaweeds fulfill these requirements. This review presents the results of in vitro and in vivo experimental and clinical studies about the effectiveness of these compounds in combating influenza infection and explains the necessity of their use as a potential basis for the creation of new drugs with a broad spectrum of activity.

scholarly journals In vivo effector function of influenza virus-specific cytotoxic T lymphocyte clones is highly specific.

1984 ◽  
Vol 160 (3) ◽  
pp. 814-826 ◽  
Author(s):  
A E Lukacher ◽  
V L Braciale ◽  
T J Braciale
Keyword(s):  
Influenza Virus ◽  
Adoptive Transfer ◽  
Defense Mechanism ◽  
Cytotoxic T Lymphocyte ◽  
Influenza Infection ◽  
Complete Recovery ◽  
Antiviral Effect ◽  
Virus Subtype

Cloned lines of murine cytotoxic T lymphocytes (CTL) directed to type A influenza virus confer complete protection upon adoptive transfer to syngeneic mice lethally infected by influenza virus. The exquisite specificity exhibited by a subtype-specific cloned CTL in culture is reflected in its capacity to eliminate pulmonary virus and mediate recovery only in those mice infected by the virus subtype recognized by this cloned line in vitro. A cross-reactive CTL cloned line protects mice infected by either of two influenza virus subtypes. In mice dually infected with two virus subtypes, the subtype-specific CTL clone only reduces lung virus levels of the recognized virus subtype and cannot prevent these mice from dying. In contrast, adoptive transfer of the cross-reactive CTL clone into mice simultaneously infected with two virus subtypes results in reduction of pulmonary titers of both subtypes and promotes complete recovery. These results directly implicate CTL as an important antiviral defense mechanism in experimental influenza infection. In addition, these results indicate that both the induction and expression of antiviral effector activity by CTL in vivo is highly specific and therefore favor the concept that CTL express their antiviral effect in vivo by direct cytolysis of infected cells.

scholarly journals Distinct Contributions of Vaccine-Induced Immunoglobulin G1 (IgG1) and IgG2a Antibodies to Protective Immunity against Influenza

2006 ◽  
Vol 13 (9) ◽  
pp. 981-990 ◽  
Author(s):  
Victor C. Huber ◽  
Raelene M. McKeon ◽  
Martha N. Brackin ◽  
Laura A. Miller ◽  
Rachael Keating ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Neutralizing Antibodies ◽  
Protective Immunity ◽  
Influenza Infection ◽  
Enzyme Linked Immunosorbent Assay ◽  
Replicon Particle ◽  
Antibody Isotypes ◽  
The Individual

ABSTRACT Vaccination represents the most effective form of protection against influenza infection. While neutralizing antibodies are typically measured as a correlate of vaccine-induced protective immunity against influenza, nonneutralizing antibodies may contribute to protection or amelioration of disease. The goal of this study was to dissect the individual contributions of the immunoglobulin G1 (IgG1) and IgG2a antibody isotypes to vaccine-induced immunity against influenza virus. To accomplish this, we utilized an influenza vaccine regimen that selectively enhanced IgG1 or IgG2a antibodies by using either DNA or viral replicon particle (VRP) vectors expressing influenza virus hemagglutinin (HA) (HA-DNA or HA-VRP, respectively). After HA-DNA vaccination, neutralizing antibodies were detected by both in vitro (microneutralization) and in vivo (lung viral titer) methods and were associated with increased IgG1 expression by enzyme-linked immunosorbent assay (ELISA). Vaccination with HA-VRP did not strongly stimulate either neutralizing or IgG1 antibodies but did induce IgG2a antibodies. Expression of IgG2a antibodies in this context correlated with clearance of virus and increased protection against lethal influenza challenge. Increased induction of both antibody isotypes as measured by ELISA was a better correlate for vaccine efficacy than neutralization alone. This study details separate but important roles for both IgG1 and IgG2a expression in vaccination against influenza and argues for the development of vaccine regimens that stimulate and measure expression of both antibody isotypes.

scholarly journals Gentamicin Induced Microbiome Adaptations Associate With Increased BCAA Levels and Enhance Severity of Influenza Infection

2021 ◽  
Vol 11 ◽  
Author(s):  
Yakun Sun ◽  
Zhili He ◽  
Jiajia Li ◽  
Saisai Gong ◽  
Shunzong Yuan ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Gut Microbiota ◽  
Influenza Infection ◽  
Alpha Diversity ◽  
Virus Infections ◽  
Bone Marrow Derived Cells ◽  
Branched Chain ◽  
Lung Immunity

Involvement of gut microbiota in pulmonary disease by the gut-lung axis has been widely observed. However, the cross-talk messengers between respiratory mucosal immunity and gut microbiota are largely unknown. Using selective pharmacologic destruction of gut microenvironment mouse models, we found gut microbiota displayed significantly lower alpha diversity and relative abundance of bacteria in Gentamicin treated mice. Metagenomic studies revealed functional differences in gut bacteria in altering metabolic profiles in mice blood. Branched-chain amino acids (BCAAs) are the essential factors linked between gut and lung. During this process, selective destruction of gut microbiota by Gentamicin induced high levels of BCAAs, and the high levels of BCAAs impacted the lung immunity against influenza virus. In vivo, Gentamicin-treated mice or mice fed with high BCAAs diets displayed reduced survival. At the sites of infection, the number of CD11b+Ly6G+ cells decreased, and CD8+ T cells increased accompanied by exuberant expression of pro-inflammatory cytokines could result in tissue damage. CD11b+Ly6G+ cells transplantation conferred remarkable protection from influenza virus infections. In vitro, BCAAs promoted bone marrow-derived cells differentiation to dendritic cells. Taken together, these findings demonstrate that Gentamicin induced disruption of the gut microbiota leads to increased BCAA levels that suppress CD11b+Ly6c+ cell development in association with overactive CD8+ T responses which may contribute to enhanced severity of the viral infection.

scholarly journals A Novel Sulfonated Derivative of β-Cyclodextrin Effectively Inhibits Influenza A Virus Infection in vitro and in vivo

Acta Naturae ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 20-30 ◽  
Author(s):  
E. P. Goncharova ◽  
Y. A. Kostyro ◽  
A. V. Ivanov ◽  
M. A. Zenkova
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
High Efficiency ◽  
Influenza Infection ◽  
Lethal Infection ◽  
Novel Drugs ◽  
Infected Cells ◽  
Low Toxicity

The development of novel drugs against the influenza virus with high efficiency and low toxicity is an urgent and important task. Previous reports have demonstrated that compounds based on sulfo derivatives of oligo- and polysaccharides possess high antiviral activity. In this study, we have examined the ability of a novel sulfonated derivative of -cyclodextrin (KS-6469) to inhibit the influenza virus A/WSN/33 (H1N1) infection in vitro and in vivo. The antiviral potential of KS-6469 against the influenza virus was evaluated in Madin-Darby Canine Kidney epithelial cells treated with serially diluted KS-6469. We found out that KS-6469 completely inhibited viral reproduction after treatment of the infected cells with the compound for 48 h. Our data show that double intranasal treatment of mice with KS-6469 fully protected the animals from a lethal infection and significantly decreased the viral titers in the lungs of the infected animals. Thus, the novel sulfonated -cyclodextrin derivative KS-6469 is a promising candidate for the development of antiviral drugs for preventing and treating the influenza infection.

scholarly journals Potent and Broad-Spectrum Antimicrobial Activity of Analogs from the Scorpion Peptide Stigmurin

2019 ◽  
Vol 20 (3) ◽  
pp. 623 ◽  
Author(s):  
Bruno Amorim-Carmo ◽  
Alessandra Daniele-Silva ◽  
Adriana M. S. Parente ◽  
Allanny A. Furtado ◽  
Eneas Carvalho ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Broad Spectrum ◽  
Therapeutic Potential ◽  
Scorpion Venom ◽  
Rational Drug Design ◽  
Biologically Active ◽  
New Drugs ◽  
Structural Conformation ◽  
Native Peptide

Scorpion venom constitutes a rich source of biologically active compounds with high potential for therapeutic and biotechnological applications that can be used as prototypes for the design of new drugs. The aim of this study was to characterize the structural conformation, evaluate the antimicrobial activity, and gain insight into the possible action mechanism underlying it, for two new analog peptides of the scorpion peptide Stigmurin, named StigA25 and StigA31. The amino acid substitutions in the native sequence for lysine residues resulted in peptides with higher positive net charge and hydrophobicity, with an increase in the theoretical helical content. StigA25 and StigA31 showed the capacity to modify their structural conformation according to the environment, and were stable to pH and temperature variation—results similar to the native peptide. Both analog peptides demonstrated broad-spectrum antimicrobial activity in vitro, showing an effect superior to that of the native peptide, being non-hemolytic at the biologically active concentrations. Therefore, this study demonstrates the therapeutic potential of the analog peptides from Stigmurin and the promising approach of rational drug design based on scorpion venom peptide to obtain new anti-infective agents.

scholarly journals Marine Algae Metabolites as Promising Therapeutics for the Prevention and Treatment of HIV/AIDS

Metabolites ◽  
2019 ◽  
Vol 9 (5) ◽  
pp. 87 ◽  
Author(s):  
Natalya N. Besednova ◽  
Tatyana N. Zvyagintseva ◽  
Tatyana A. Kuznetsova ◽  
Ilona D. Makarenkova ◽  
Tatyana P. Smolina ◽  
...  
Keyword(s):  
Marine Algae ◽  
High Efficiency ◽  
Wide Spectrum ◽  
Antiretroviral Drugs ◽  
Biologically Active ◽  
New Drugs ◽  
Sulfated Polysaccharides ◽  
Natural Immunity

This review presents an analysis of works devoted to the anti-human immunodeficiency virus (HIV) activity of algae metabolites—sulfated polysaccharides (fucoidans, carrageenans), lectins, laminarans, and polyphenols. Despite the presence of a significant number of antiretroviral drugs, the development of new therapeutic and prophylactic agents against this infection remains very urgent problem. This is due to the variability of HIV, the absence of an animal model (except monkeys) and natural immunity to this virus and the toxicity of therapeutic agents and their high cost. In this regard, the need for new therapeutic approaches and broad-spectrum drugs, which in addition to antiviral effects can have anti-inflammatory, antioxidant, and immunomodulatory effects, and to which the minimum resistance of HIV strains would be formed. These requirements meet the biologically active substances of marine algae. The results of experimental and clinical studies conducted in vitro and in vivo are presented, and the issues of the anti-HIV activity of these compounds are considered depending on their structural features. On the whole, the presented data prove the high efficiency of seaweed metabolites and justify the possibility of their use as a potential basis for the development of new drugs with a wide spectrum of activity.

scholarly journals Morpholine derivatives as potential agents for neurological manifestations of nervous system diseases

2020 ◽  
Vol 2 (1) ◽  
pp. 16-35
Author(s):  
Veronika A. Prikhodko ◽  
Yuriy I. Sysoev ◽  
Sergey Okovityi
Keyword(s):  
Nervous System ◽  
Social Impact ◽  
Neurological Diseases ◽  
Clinical Manifestations ◽  
Biologically Active ◽  
New Drugs ◽  
In Vivo Studies ◽  
Morpholine Derivatives

Diseases of the nervous system, especially those of vascular, traumatic, and neurodegenerative nature, are characterized by high prevalence, disability and mortality rates, and therefore have a particularly big medical and social impact. Currently, pharmacotherapy options for these diseases are limited to a relatively small number of clinically proven drugs, which is largely due to the difficulties associated with the translation of preclinical studies results. This explains the essential importance of discovering and developing new drugs, both effective and safe, that could be used to reduce clinical manifestations of neurological disorders. The present review is aimed to give a detailed account of several biologically active derivatives of morpholine, a six-membered heterocyclic compound. As demonstrated by a number of in vitro and in vivo studies using cell and animal models, morpholine derivatives should be considered viable drug candidates for a broad range of neurological diseases.

scholarly journals Aglycone polyether ionophores as broad-spectrum agents inhibit multiple enveloped viruses including SARS-CoV-2 in vitro and successfully cure JEV infected mice

2020 ◽  
Author(s):  
Jia-Qi Li ◽  
Minjian Huang ◽  
Ya-Nan Zhang ◽  
Ran Liu ◽  
Zhe-Rui Zhang ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Broad Spectrum ◽  
Chikungunya Virus ◽  
Mechanistic Studies ◽  
Global Risk ◽  
Enveloped Viruses ◽  
Zoonotic Viruses ◽  
Full Protection

AbstractInfections with zoonotic viruses, such as flaviviruses, influenza virus, and the SARS-CoV-2 pandemic coronavirus constitute an increasing global risk. Hence, an urgent need exists for the development of broad-spectrum antivirals to prevent such outbreaks. Here, we show that the maduramycin and CP-80,219 aglycone polyether ionophores exhibit effective broad-spectrum antiviral activity, against various viruses, including Japanese encephalitis virus (JEV), Dengue virus (DENV), Zika virus (ZIKV), and Chikungunya virus (CHIKV), while also exhibiting promising activity against PR8 influenza virus and SARS-CoV-2. Moreover, liposome-encapsulated maduramycin and CP-80,219 provide full protection for mice from infection with JEV in vivo. Mechanistic studies suggest that aglycone polyether ionophores primarily inhibit the viral replication step without blocking endosome acidification to promote the fusion between viral and cellular membranes. The successful application of liposomes containing aglycone polyether ionophores in JEV-infected mice offers hope to the development of broad-spectrum antiviral drugs like penicillin back to 1940s.

scholarly journals A molecularly engineered antiviral banana lectin inhibits fusion and is efficacious against influenza virus infection in vivo

2020 ◽  
Vol 117 (4) ◽  
pp. 2122-2132 ◽  
Author(s):  
Evelyn M. Covés-Datson ◽  
Steven R. King ◽  
Maureen Legendre ◽  
Auroni Gupta ◽  
Susana M. Chan ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Broad Spectrum ◽  
Parent Compound ◽  
Influenza Virus Infection ◽  
Amino Acid Mutation ◽  
Spectrum Activity ◽  
Therapeutic Administration ◽  
Broad Spectrum Activity

There is a strong need for a new broad-spectrum antiinfluenza therapeutic, as vaccination and existing treatments are only moderately effective. We previously engineered a lectin, H84T banana lectin (H84T), to retain broad-spectrum activity against multiple influenza strains, including pandemic and avian, while largely eliminating the potentially harmful mitogenicity of the parent compound. The amino acid mutation at position 84 from histidine to threonine minimizes the mitogenicity of the wild-type lectin while maintaining antiinfluenza activity in vitro. We now report that in a lethal mouse model H84T is indeed nonmitogenic, and both early and delayed therapeutic administration of H84T intraperitoneally are highly protective, as is H84T administered subcutaneously. Mechanistically, attachment, which we anticipated to be inhibited by H84T, was only somewhat decreased by the lectin. Instead, H84T is internalized into the late endosomal/lysosomal compartment and inhibits virus–endosome fusion. These studies reveal that H84T is efficacious against influenza virus in vivo, and that the loss of mitogenicity seen previously in tissue culture is also seen in vivo, underscoring the potential utility of H84T as a broad-spectrum antiinfluenza agent.

Nitration of human plasminogen by RAW 264.7 macrophages reduces streptokinase-induced plasmin activity

2006 ◽  
Vol 44 (2) ◽  
Author(s):  
Chinhnam Hathuc ◽  
Ricardo Hermo ◽  
John Schulze ◽  
Alejandro Gugliucci
Keyword(s):  
Nitrosative Stress ◽  
Inflammatory Cells ◽  
New Drugs ◽  
Plasmin Activity ◽  
New Therapeutic Approaches ◽  
Raw264.7 Macrophages ◽  
Human Plasminogen ◽  
Functional Inactivation

AbstractDespite many years of study, clinical trials of new drugs to prevent thrombosis have often been disappointing. Part of the problem lies in our incomplete understanding of the regulation of plasminogen activation and/or inhibition in vivo. We have previously shown that in vitro nitration of plasminogen in plasma by peroxynitrite resulted in decreased plasmin activity. We hypothesized that macrophages may be agents of plasminogen nitration and designed this study to prove this hypothesis. We first better characterized our previous observations using purified plasminogen instead of whole plasma, studied the time and concentration dependence of these reactions, and co-incubated plasminogen with macrophages, as well as with non-inflammatory cells as controls, to assess nitration and impaired activity. When plasminogen (10μmol/L) is incubated in the presence of SIN-1 (0.01–2mmol/L), plasmin activity (generated by streptokinase) is reduced in a time- and concentration-dependent fashion. We performed experiments incubating human plasminogen in the presence of murine RAW264.7 macrophages, allowing for free diffusion of reactive oxygen species, while preventing the action of proteases. In this way we show that incubation of plasminogen with macrophages also decreases plasmin activity, while increasing nitration of the molecule, an effect that is already apparent after 2h and reaches a plateau of 60% inhibition after 24h of incubation. This effect appears specific for macrophages, since 31EG4 murine mammary cells used in parallel and under the same conditions failed to produce any deleterious changes in plasminogen. Our data on quick functional inactivation of plasminogen by nitration, mediated by macrophages, adds a new pathophysiological dimension to our previous work showing plasminogen as a target for peroxynitrite damage. Nitrosative stress may be implicated in impaired fibrinolysis. New therapeutic approaches for nitrosative stress in atherosclerosis and diabetes should limit the formation of superoxides and peroxynitrite.

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