490 results on '"antiviral effect"'
Search Results
452. Human recombinant myeloperoxidase antiviral activity on cytomegalovirus
- Author
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El Messaoudi, Kamal, Verheyden, Ann-Michèle, Thiry, Lise, Fourez, Sylvie, Tasiaux, Nicole, Bollen, Alex, Moguilevsky, Nicole, El Messaoudi, Kamal, Verheyden, Ann-Michèle, Thiry, Lise, Fourez, Sylvie, Tasiaux, Nicole, Bollen, Alex, and Moguilevsky, Nicole
- Abstract
SCOPUS: ar.j, FLWIN, info:eu-repo/semantics/published
- Published
- 2002
453. Role of nitric oxide on the replication of viral haemorrhagic septicemia virus (VHSV), a fish rhabdovirus
- Author
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Tafalla, Carolina, Figueras Huerta, Antonio, Novoa, Beatriz, Tafalla, Carolina, Figueras Huerta, Antonio, and Novoa, Beatriz
- Abstract
In the present work, we have studied the role of nitric oxide (NO) on the replication of viral haemorrhagic septicemia virus (VHSV), a virus which produces high mortalities in fish aquaculture worldwide and that is known to replicate in turbot (Scophthalmus maximus) head kidney macrophages. Viral infection of turbot kidney macrophages in vitro induced an up-regulation of NO production and we have tested whether this endogenous NO production induced by VHSV on macrophages had an antiviral effect using the NO synthase inhibitor, N-!-nitro-L-arginine (LNAME). When L-NAME was added to the VHSV-infected cultures, no increase on VHSV titer was observed, eventhough the inhibitor was capable of decreasing NO production. When exogenous NO was apported by the nitric oxide donor, glycerin trinitrate (GTN) an antiviral effect on VHSV was observed. The NO donor significantly inhibited VHSV replication on a turbot fibroblast cell line (TV-1) and on turbot kidney macrophages.
- Published
- 1999
454. Antiviral Effect of IDO in Mouse Fibroblast Cells During Influenza Virus Infection.
- Author
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Li F and Karlsson H
- Subjects
- 3-Hydroxyanthranilate 3,4-Dioxygenase genetics, Animals, Antiviral Agents pharmacology, Gene Expression Regulation, Viral, Gene Knockdown Techniques, Humans, Indoleamine-Pyrrole 2,3,-Dioxygenase antagonists & inhibitors, Influenza A virus physiology, Interferon-beta genetics, Mice, NIH 3T3 Cells, Orthomyxoviridae Infections virology, Tryptophan metabolism, Indoleamine-Pyrrole 2,3,-Dioxygenase pharmacology, Influenza A virus drug effects, Orthomyxoviridae Infections enzymology, Viral Proteins genetics, Virus Replication drug effects
- Abstract
While upregulation of 2,3-dioxygenase (IDO) accompanied by degradation of tryptophan along the kynurenine pathway have been reported to exert antimicrobial effects against a wide range of infectious agents, its role in the replication of influenza A virus remains uncertain. We performed experiments using influenza A/WSN/33 virus infection of mouse fibroblast cell-line (NIH-3T3) to study the effects of IDO on viral replication. Influenza infection resulted in prominent elevations of transcripts encoding IDO, interferon (IFN)-β, and segment 8 of the virus in NIH-3T3 cells. Introduction of siRNA targeted against IDO followed by infection resulted in further increased levels of viral RNA without altering IFN-β expression. Inhibition of IDO during the infection also resulted in reduction of virus-driven upregulation of 3-hydroxyanthranilate 3,4-dioxygenase (HAAO), but not kynurenine 3-monooxygenase (KMO), which are enzymes downstream in the kynurenine pathway. Thus, induction of IDO appears to contribute to limiting replication of the WSN/33 strain of influenza A virus in murine NIH-3T3 cells.
- Published
- 2017
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455. Eupatorium fortunei and Its Components Increase Antiviral Immune Responses against RNA Viruses.
- Author
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Choi JG, Lee H, Hwang YH, Lee JS, Cho WK, and Ma JY
- Abstract
Eupatorium fortunei (EF) has long been used as herbal medicine in Korea, China, and Asian countries to treat a variety of diseases. Recent studies have reported that EF has anti-metastatic, anti-angiogenic, anti-bacterial, and anti-oxidant activities, as well as activities against malignant metastatic human cancers. The effect of EF and its components on viruses has not been reported. In the present study, the antiviral activity and mechanism of action of an aqueous extract of EF (WEF) and its components were evaluated in vitro . We found that pretreatment with WEF markedly reduced viral replication, as evaluated using a green fluorescent protein (GFP)-tagged virus (influenza A virus, Newcastle disease virus, and vesicular stomatitis virus) in murine RAW 264.7 macrophage cells. We demonstrated that WEF induces the production of type I IFN including pro-inflammatory cytokines. Additionally, we identified the active anti-viral components of WEF as quercetin, psoralen, and quercitrin. Thus, WEF and its active components are immunomodulators of the innate immune response in murine macrophages, a finding that is potentially useful to developing prophylactic or therapeutic treatments against a range of viruses.
- Published
- 2017
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- View/download PDF
456. Antiviral effects of Retro-2 cycl and Retro-2.1 against Enterovirus 71 in vitro and in vivo.
- Author
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Dai W, Wu Y, Bi J, Lu X, Hou A, Zhou Y, Sun B, Kong W, Barbier J, Cintrat JC, Gao F, Gillet D, Su W, and Jiang C
- Subjects
- Animals, Antiviral Agents toxicity, Benzamides toxicity, Cell Line, Cell Survival drug effects, Disease Models, Animal, Enterovirus A, Human physiology, Humans, Inhibitory Concentration 50, Mice, Inbred BALB C, Microbial Sensitivity Tests, Survival Analysis, Thiophenes toxicity, Antiviral Agents administration & dosage, Antiviral Agents pharmacology, Benzamides administration & dosage, Benzamides pharmacology, Enterovirus A, Human drug effects, Hand, Foot and Mouth Disease drug therapy, Thiophenes administration & dosage, Thiophenes pharmacology, Virus Release drug effects
- Abstract
Enterovirus 71 (EV71) is one of the causative pathogens of hand, foot and mouth disease (HFMD), especially the form associated with fatal neurological disorders. Sustained outbreaks of EV71 infections remain a serious health threat worldwide. However, no antiviral agent against EV71 for clinical therapy has been approved. Retro-2
cycl and Retro-2.1 are inhibitors of several pathogens specifically targeting the intracellular vesicle transport, which also participates in the EV71 lifecycle processes including progeny virus release. Here, we reported that Retro-2cycl and Retro-2.1, respectively, could inhibit EV71 infection with 50% effective concentrations of 12.56 μM and 0.05 μM in a cytopathic effect inhibition assay and showed relatively low cytotoxicity with 50% cytotoxicity concentrations of more than 500 μM and 267.80 μM. Preliminary mechanism studies revealed that Retro-2cycl and Retro-2.1 did not inhibit EV71 protein synthesis or RNA replication but could block progeny EV71 release specifically. Furthermore, administration of Retro-2cycl at the dose of 10 mg/kg significantly protected 90% of newborn mice from lethal EV71 challenge. Consequently, our results for the first time identified Retro-2cycl and Retro-2.1 as effective inhibitors of EV71 as well as lead compounds, which would contribute to anti-EV71 drug development. We also identified progeny virus release and the intracellular vesicle transport as antiviral targets for EV71., (Copyright © 2017 Elsevier B.V. All rights reserved.)- Published
- 2017
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457. Lignins and Their Derivatives with Beneficial Effects on Human Health.
- Author
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Vinardell MP and Mitjans M
- Subjects
- Animals, Antioxidants pharmacology, Antioxidants therapeutic use, Antiviral Agents pharmacology, Antiviral Agents therapeutic use, Drug Delivery Systems, Humans, Immunologic Factors pharmacology, Immunologic Factors therapeutic use, Lignin analogs & derivatives, Lignin therapeutic use, Health Promotion, Lignin pharmacology
- Abstract
A review of the pharmacological applications of lignins provides evidence of their protective role against the development of different diseases. In many cases, the effects of lignins could be explained by their antioxidant capacity. Here, we present a systematic review of the literature from the period 2010-2016 which provides information concerning new applications of lignins derived from recent research. The most promising findings are reported, including the methodologies employed and results obtained with lignins or their derivatives which may improve human health. We highlight potential applications in the treatment of obesity, diabetes, thrombosis, viral infections and cancer. Moreover, we report both that lignins can be used in the preparation of nanoparticles to deliver different drugs and also their use in photoprotection., Competing Interests: The authors declare no conflict of interest.
- Published
- 2017
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458. Coptidis Rhizoma extract inhibits replication of respiratory syncytial virus in vitro and in vivo by inducing antiviral state.
- Author
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Lee BH, Chathuranga K, Uddin MB, Weeratunga P, Kim MS, Cho WK, Kim HI, Ma JY, and Lee JS
- Subjects
- Animals, Berberine Alkaloids pharmacology, Cell Line, Coptis chinensis, Humans, Immunologic Factors pharmacology, Interferon-beta metabolism, Interleukin-6 metabolism, Mice, Mice, Inbred BALB C, Plant Extracts pharmacology, Respiratory Syncytial Virus, Human drug effects, Antiviral Agents pharmacology, Drugs, Chinese Herbal pharmacology, Respiratory Syncytial Virus Infections drug therapy, Respiratory Syncytial Virus, Human growth & development, Virus Replication drug effects
- Abstract
Coptidis Rhizoma is derived from the dried rhizome of Ranunculaceous plants and is a commonly used traditional Chinese medicine. Although Coptidis Rhizoma is commonly used for its many therapeutic effects, antiviral activity against respiratory syncytial virus (RSV) has not been reported in detail. In this study, we evaluated the antiviral activities of Coptidis Rhizoma extract (CRE) against RSV in human respiratory tract cell line (HEp2) and BALB/c mice. An effective dose of CRE significantly reduces the replication of RSV in HEp2 cells and reduces the RSV-induced cell death. This antiviral activity against RSV was through the induction of type I interferon-related signaling and the antiviral state in HEp2 cells. More importantly, oral administration of CRE exhibited prophylactic effects in BALB/c mice against RSV. In HPLC analysis, we found the presence of several compounds in the aqueous fraction and among them; we confirmed that palmatine was related to the antiviral properties and immunemodulation effect. Taken together, an extract of Coptidis Rhizoma and its components play roles as immunomodulators and could be a potential source as promising natural antivirals that can confer protection to RSV. These outcomes should encourage further allied studies in other natural products.
- Published
- 2017
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459. Development of a Novel Site-Specific Pegylated Interferon Beta for Antiviral Therapy of Chronic Hepatitis B Virus.
- Author
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Tsuge M, Uchida T, Hiraga N, Kan H, Makokha GN, Abe-Chayama H, Miki D, Imamura M, Ochi H, Hayes CN, Shimozono R, Iwamura T, Narumi H, Suzuki T, Kainoh M, Taniguchi T, and Chayama K
- Subjects
- Animals, Cell Line, Tumor, Chemokine CXCL10 biosynthesis, DNA, Circular metabolism, DNA, Viral metabolism, Hep G2 Cells, Humans, Mice, Mice, SCID, Mice, Transgenic, Recombinant Proteins pharmacology, Treatment Outcome, Viral Load drug effects, Virus Replication drug effects, Antiviral Agents pharmacology, Hepatitis B Surface Antigens metabolism, Hepatitis B virus drug effects, Hepatitis B, Chronic drug therapy, Interferon-alpha pharmacology, Polyethylene Glycols pharmacology
- Abstract
Although nucleot(s)ide analogues and pegylated interferon alpha 2a (PEG-IFN-α2a) can suppress hepatitis B virus (HBV) replication, it is difficult to achieve complete HBV elimination from hepatocytes. A novel site-specific pegylated recombinant human IFN-β (TRK-560) was recently developed. In the present study, we evaluated the antiviral effects of TRK-560 on HBV replication in vitro and in vivo. In vitro and in vivo HBV replication models were treated with antivirals including TRK-560, and changes in HBV markers were evaluated. To analyze antiviral mechanisms, cDNA microarray analysis and an enzyme-linked immunoassay (ELISA) were performed. TRK-560 significantly suppressed the production of intracellular HBV replication intermediates and extracellular HBV surface antigen (HBsAg) ( P < 0.001 and P < 0.001, respectively), and the antiviral effects of TRK-560 were enhanced in combination with nucleot(s)ide analogues, such as entecavir and tenofovir disoproxil fumarate. The reduction in HBV DNA levels by TRK-560 treatment was significantly higher than that by PEG-IFN-α2a treatment both in vitro and in vivo ( P = 0.004 and P = 0.046, respectively), and intracellular HBV covalently closed circular DNA (cccDNA) reduction by TRK-560 treatment was also significantly higher than that by PEG-IFN-α2a treatment in vivo ( P = 0.0495). cDNA microarrays and ELISA for CXCL10 production revealed significant differences between TRK-560 and PEG-IFN-α2a in the induction potency of interferon-stimulated genes. TRK-560 shows a stronger antiviral potency via higher induction of interferon-stimulated genes and stronger stimulation of immune cell chemotaxis than PEG-IFN-α2a. As HBsAg loss and HBV cccDNA eradication are important clinical goals, these results suggest a potential role for TRK-560 in the development of more effective treatment for chronic hepatitis B infection., (Copyright © 2017 American Society for Microbiology.)
- Published
- 2017
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460. Different antiviral effects of IFNα and IFNβ in an HBV mouse model.
- Author
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Zhou Y, Li S, Tang Z, Xu C, Huang S, Wu J, Dittmer U, Dickow J, Sutter K, Lu M, Yang D, and Song J
- Subjects
- Animals, Cytokines genetics, Cytokines metabolism, Disease Models, Animal, Gene Expression, Gene Transfer Techniques, Hepatitis B drug therapy, Hepatitis B Core Antigens blood, Hepatitis B Core Antigens genetics, Hepatitis B virus classification, Hepatitis B virus genetics, Humans, Interferon-alpha blood, Interferon-alpha pharmacology, Interferon-beta blood, Interferon-beta pharmacology, Liver metabolism, Liver pathology, Liver virology, Mice, Plasmids administration & dosage, Plasmids genetics, RNA, Messenger genetics, Transfection, Ubiquitins genetics, Ubiquitins metabolism, Viral Load, Virus Replication drug effects, Antiviral Agents pharmacology, Hepatitis B genetics, Hepatitis B virology, Hepatitis B virus drug effects, Interferon-alpha genetics, Interferon-beta genetics
- Abstract
Interferons α and β (IFNα and IFNβ) are type I interferons produced by the host to control pathogen propagation. However, only a minority of chronic hepatitis B (CHB) patients generate a sustained response after treatment with recombinant IFNα. The anti-HBV effect of IFNβ and the underlying mechanism are not well-understood. Here, we compared the antiviral activities of IFNα and IFNβ by application of IFNα or IFNβ expression plasmids using the well-established HBV hydrodynamic injection (HI) mouse model. Injection of IFNα expression plasmid could significantly reduce HBV serum markers including HBsAg, HBeAg and HBV DNA as well as the number of HBcAg positive cells in the liver, while IFNβ showed only a weak inhibition of HBV replication. In contrast to IFNβ, IFNα resulted in elevated expression levels of IFN stimulated genes (ISGs) as well as the proinflammatory cytokine interleukin 6 (IL6) in the liver. Moreover, IFNβ treated mice showed higher expression levels of the anti-inflammatory cytokines IL10 and TGFβ in the liver compared to IFNα. Our results demonstrated that both IFNα and IFNβ exert antiviral activities against HBV in HI mouse model, but IFNα is more effective than IFNβ., (Copyright © 2016 Elsevier GmbH. All rights reserved.)
- Published
- 2017
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461. Effect of silver nanoparticles on the metabolic rate, hematological response, and survival of juvenile white shrimp Litopenaeus vannamei.
- Author
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Juarez-Moreno K, Mejía-Ruiz CH, Díaz F, Reyna-Verdugo H, Re AD, Vazquez-Felix EF, Sánchez-Castrejón E, Mota-Morales JD, Pestryakov A, and Bogdanchikova N
- Subjects
- Adolescent, Animals, Aquaculture methods, Humans, Oxygen Consumption drug effects, Particle Size, Penaeidae virology, Survival Analysis, White spot syndrome virus 1 growth & development, Antiviral Agents toxicity, Hemocytes drug effects, Metal Nanoparticles toxicity, Penaeidae drug effects, Penaeidae metabolism, Silver toxicity
- Abstract
White spot syndrome virus (WSSV) is highly lethal and contagious in shrimps; its outbreaks causes an economic crisis for aquaculture. Several attempts have been made to treat this disease; however, to date, there is no effective cure. Because of their antimicrobial activities, silver nanoparticles (AgNPs) are the most studied nanomaterial. Although the antiviral properties of AgNPs have been studied, their antiviral effect against viral infection in aquaculture has not been reported. The AgNPs tested herein are coated with polyvinylpyrrolidone (PVP) and possess multiple international certifications for their use in veterinary and human applications. The aim of this work was to evaluate the survival rate of juvenile white shrimps (Litopenaeus vannamei) after the intramuscular administration of AgNPs. For this, different concentrations of metallic AgNPs and PVP alone were injected into the organisms. After 96 h of administration, shrimp survival was more than 90% for all treatments. The oxygen consumption routine rate and total hemocyte count remained unaltered after AgNP injection, reflecting no stress caused. We evaluated whether AgNPs had an antiviral effect in shrimps infected with WSSV. The results revealed that the survival rate of WSSV-infected shrimps after AgNP administration was 80%, whereas the survival rate of untreated organisms was only 10% 96 h after infection. These results open up the possibility to explore the potential use of AgNPs as antiviral agents for the treatment of diseases in aquaculture organisms, particularly the WSSV in shrimp culture., (Copyright © 2016 Elsevier Ltd. All rights reserved.)
- Published
- 2017
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462. Protective effects of Phaseolus vulgaris lectin against viral infection in Drosophila.
- Author
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Ekowati H, Arai J, Damana Putri AS, Nainu F, Shiratsuchi A, and Nakanishi Y
- Subjects
- Animals, Drosophila genetics, Drosophila virology, Phaseolus, RNA, Messenger drug effects, RNA, Messenger metabolism, Receptors, Immunologic drug effects, Receptors, Immunologic genetics, Viral Load drug effects, Dicistroviridae, Drosophila drug effects, Mitogens pharmacology, Phytohemagglutinins pharmacology, Survival Rate, Virus Diseases virology
- Abstract
Phytohemagglutinin (PHA) isolated from the family of Phaseolus vulgaris beans is a promising agent against viral infection; however, it has not yet been demonstrated in vivo. We herein investigated this issue using Drosophila as a host. Adult flies were fed lectin approximately 12 h before they were subjected to a systemic viral infection. After a fatal infection with Drosophila C virus, death was delayed and survival was longer in flies fed PHA-P, a mixture of L4, L3E1, and L2E2, than in control unfed flies. We then examined PHA-L4, anticipating subunit L as the active form, and confirmed the protective effects of this lectin at markedly lower concentrations than PHA-P. In both experiments, lectin feeding reduced the viral load prior to the onset of fly death. Furthermore, we found a dramatic increase in the levels of the mRNAs of phagocytosis receptors in flies after feeding with PHA-L4 while a change in the levels of the mRNAs of antimicrobial peptides was marginal. We concluded that P. vulgaris PHA protects Drosophila against viral infection by augmenting the level of host immunity.
- Published
- 2017
- Full Text
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463. Heme oxygenase-1 metabolite biliverdin, not iron, inhibits porcine reproductive and respiratory syndrome virus replication.
- Author
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Zhang A, Duan H, Li N, Zhao L, Pu F, Huang B, Wu C, Nan Y, Du T, Mu Y, Zhao Q, Sun Y, Zhang G, Hiscox JA, Zhou EM, and Xiao S
- Subjects
- Animals, Biliverdine metabolism, Heme Oxygenase-1 genetics, Iron metabolism, Porcine Reproductive and Respiratory Syndrome pathology, Porcine Reproductive and Respiratory Syndrome virology, Porcine respiratory and reproductive syndrome virus pathogenicity, Swine, Heme Oxygenase-1 metabolism, Porcine Reproductive and Respiratory Syndrome genetics, Porcine respiratory and reproductive syndrome virus genetics, Virus Replication genetics
- Abstract
Porcinereproductiveandrespiratorysyndromevirus (PRRSV) causes significant economic losses to the pork industry worldwide. Previously, we demonstrated that heme oxygenase-1 (HO-1) interferes with PRRSV replication. To elucidate the mechanisms involved, here we assess whether the HO-1 downstream metabolites biliverdin (BV) and/or iron mediate the HO-1 antiviral effect. We demonstrate a BV concentration-dependent suppression of PRRSV replication and show that virions are not directly inactivated by BV. Additionally, BV or N-acetyl cysteine (NAC) significantly reduced reactive oxygen species (ROS) in PRRSV-infected MARC-145 cells; however, because NAC did not reduce viral load, the BV antiviral effect is independent of decreased ROS levels. Moreover, a secondary metabolite of BV, bilirubin (BR), specifically mediates this anti-PRRSV activity via a nitric oxide (NO)-dependent cGMP/PKG signaling pathway. While increased iron via addition of FeCl
3 did not interfere with PRRSV replication, iron depletion by deferoxamine (DFO) after cobalt-protoporphyrin IX induction of HO-1 did not restore PRRSV replication. Collectively, our findings identify a HO-1-BV/BR-NO-cGMP/PKG cascade as a novel pathway underlying the host cell antiviral effect. These results provide a unique insight into the molecular mechanisms underlying the antiviral effects of the stress-responsive protein HO-1 during PRRSV infection., (Copyright © 2016 Elsevier Inc. All rights reserved.)- Published
- 2017
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464. Antiviral effect of a polysaccharide from Sclerotium glucanicum towards herpes simplex virus type 1 infection
- Author
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Magda Marchetti, Valeria Pietropaolo, Annamarta Degener, Lucilla Seganti, Rosario Nicoletti, Nicola Orsi, and S. Pisani
- Subjects
Cell Survival ,Pharmaceutical Science ,herpes simplex virus type 1 ,Herpesvirus 1, Human ,Viral Plaque Assay ,Biology ,antiviral effect ,Polysaccharide ,medicine.disease_cause ,Virus Replication ,Antiviral Agents ,Virus ,Analytical Chemistry ,Microbiology ,scleroglucan ,Polysaccharides ,Drug Discovery ,Chlorocebus aethiops ,medicine ,Animals ,Antigens, Viral ,Glucans ,Vero Cells ,Pharmacology ,Virus quantification ,chemistry.chemical_classification ,Organic Chemistry ,Glycosidic bond ,Plants ,Membrane glycoproteins ,Herpes simplex virus ,Complementary and alternative medicine ,Viral replication ,chemistry ,Vero cell ,biology.protein ,Molecular Medicine - Abstract
Among different neutral polysaccharides from natural sources, scleroglucan from Sclerotium glucanicum significantly inhibits the replication of herpes simplex virus type 1 on Vero cells. Scleroglucan belongs to a class of exopolymers, expressed by members of genus Sclerotium and consists of a linear beta-1,3-linked glucopyranose with side chains of single glucopyranose residues linked through beta-1,6 glycosidic bonds. The effective antiviral concentration of this polysaccharide is far from the cytotoxicity threshold and consequently this natural product possesses a good selectivity index. Results obtained in experiments carried out in order to clarify the mechanism of action of this carbohydrate indicate that the block of infection occurs during the very early phases of the viral mutliplication cycle since the highest inhibitory effect took place when it was added during the attachment step. The antiviral effect of scleroglucan seems to be related to its binding with membrane glycoproteins of HSV-1 particles which impedes the complex interactions of the virus with the cell plasma membrane.
- Published
- 1996
465. Fructus Amomi Cardamomi Extract Inhibit Coxsackievirus-B3 Induced Myocarditis in Murine Myocarditis Model.
- Author
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Lee YG, Park JH, Jeon ES, Kim JH, and Lim BK
- Subjects
- Animals, Coxsackievirus Infections virology, Disease Models, Animal, Enterovirus B, Human physiology, Humans, Male, Mice, Mice, Inbred BALB C, Myocarditis virology, Virus Replication drug effects, Antiviral Agents administration & dosage, Coxsackievirus Infections drug therapy, Elettaria chemistry, Enterovirus B, Human drug effects, Myocarditis drug therapy, Plant Extracts administration & dosage
- Abstract
Coxsackievirus B3 (CVB3) is the main cause of acute myocarditis and dilated cardiomyopathy. Plant extracts are considered as useful materials to develop new antiviral drugs. We had previously selected candidate plant extracts, which showed anti-inflammatory effects. We examined the antiviral effects by using a HeLa cell survival assay. Among these extracts, we chose the Amomi Cardamomi ( Amomi ) extract, which showed strong antiviral effect and preserved cell survival in CVB3 infection. We investigated the mechanisms underlying the ability of Amomi extract to inhibit CVB3 infection and replication. HeLa cells were infected by CVB3 with or without Amomi extract. Erk and Akt activities, and their correlation with virus replication were observed. Live virus titers in cell supernatants and viral positive- and negative-strand RNA amplification were measured. Amomi extract significantly increased HeLa cell survival in different concentrations (100-10 µg/ml). CVB3 capsid protein VP1 expression (76%) and viral protease 2A-induced eIF4G1 cleavage (70%) were significantly decreased in Amomi extract (100 µg/ml) treated cells. The levels of positive- (20%) and negative-strand (80%) RNA were dramatically decreased compared with the control, as revealed by reverse transcription-PCR. In addition, Amomi extract improved mice survival (51% vs 26%) and dramatically reduced heart inflammation in a CVB3-induced myocarditis mouse model. These results suggested that Amomi extract significantly inhibited Enterovirus replication and myocarditis damage. Amomi may be developed as a therapeutic drug for Enterovirus .
- Published
- 2016
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466. Antiviral activity of KR-23502 targeting nuclear export of influenza B virus ribonucleoproteins.
- Author
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Jang Y, Lee HW, Shin JS, Go YY, Kim C, Shin D, Malpani Y, Han SB, Jung YS, and Kim M
- Subjects
- Cell Nucleus metabolism, Humans, Influenza B virus chemistry, Influenza B virus genetics, Influenza, Human drug therapy, Mutation, RNA, Viral, Ribonucleoproteins chemistry, Ribonucleoproteins genetics, Viral Proteins metabolism, Virus Replication drug effects, Active Transport, Cell Nucleus drug effects, Antiviral Agents pharmacology, Benzofurans pharmacology, Influenza B virus drug effects, Ribonucleoproteins drug effects, Viral Matrix Proteins drug effects
- Abstract
The spiro compound 5,6-dimethyl-3H,3'H-spiro(benzofuran-2,1'-isobenzofuran)-3,3'-dione (KR-23502) has antiviral activity against influenza A and more potently B viruses. The aim of this study is to elucidate its mechanism of action. Subcellular localization and time-course expression of influenza B viral proteins, nucleoprotein (NP) and matrix protein 1 (M1), showed that KR-23502 reduced their amounts within 5 h post-infection. Early steps of virus life cycle, including virus entry, nuclear localization of NP and viral RNA-dependent RNA replication, were not affected by KR-23502. Instead it interrupted a later event corresponding to nuclear export of NP and M1 proteins. Delivery of viral ribonucleoprotein (vRNP)-M1 complex has been known to be mediated by the viral nuclear export protein (NEP) through interaction with cellular chromosomal maintenance 1 (CRM1) protein. In this study, we experimentally demonstrated that the compound targets the nuclear export of vRNP. Moreover, a single mutation (aspartate to glycine) at amino acid position 54 in M1 [M1(D54G)] was detected after 18 passages in the presence of KR-23502 with a 2-fold increase in 50% effective concentration indicating that this compound has a relatively high genetic barrier to resistance. Interestingly, it was observed that proteasome-mediated degradation of M1(D54G) was attenuated by KR-23502. In conclusion, we suggest that KR-23502 shows its anti-influenza activity by downregulating NEP/CRM1-mediated nuclear export of influenza vRNP and M1. KR-23502 provides a core chemical skeleton for further structure-based design of novel antivirals against influenza viruses., (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Published
- 2016
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467. Antiviral activity of selected flavonoids against Chikungunya virus.
- Author
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Lani R, Hassandarvish P, Shu MH, Phoon WH, Chu JJ, Higgs S, Vanlandingham D, Abu Bakar S, and Zandi K
- Subjects
- Animals, Antiviral Agents chemistry, Biological Products pharmacology, Cell Line, Chikungunya virus genetics, Cricetinae, Dose-Response Relationship, Drug, Drug Evaluation, Preclinical, Flavonoids chemistry, Genotype, Inhibitory Concentration 50, Vero Cells, Virus Replication drug effects, Antiviral Agents pharmacology, Chikungunya virus drug effects, Flavonoids pharmacology
- Abstract
This study focuses on the antiviral activity of selected flavonoids against the Chikungunya virus (CHIKV), a mosquito-transmitted virus that can cause incapacitating arthritis in infected individuals. Based on the results of screening on Vero cells, the tested compounds were evaluated further with various assays, including cytotoxicity assay, virus yield assay by quantitative reverse transcription polymerase chain reaction (qRT-PCR), virus RNA replication assay with a CHIKV replicon cell line, Western blotting, and quantitative immunofluorescence assay. Baicalein, fisetin, and quercetagetin displayed potent inhibition of CHIKV infection, with 50% inhibitory concentrations [IC50] of 1.891 μg/ml (6.997 μM), 8.444 μg/ml (29.5 μM), and 13.85 μg/ml (43.52 μM), respectively, and with minimal cytotoxicity. The time-of-addition studies and various antiviral assays demonstrated that baicalein and quercetagetin mainly inhibited CHIKV binding to the Vero cells and displayed potent activity against extracellular CHIKV particles. The qRT-PCR, immunofluorescence assay, and Western blot analyses indicated that each of these flavonoids affects CHIKV RNA production and viral protein expression. These data provide the first evidence of the intracellular anti-CHIKV activity of baicalein, fisetin, and quercetagetin., (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Published
- 2016
- Full Text
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468. Antiviral activity of various interferons and pro-inflammatory cytokines in non-transformed cultured hepatocytes infected with hepatitis B virus.
- Author
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Isorce N, Testoni B, Locatelli M, Fresquet J, Rivoire M, Luangsay S, Zoulim F, and Durantel D
- Subjects
- Antigens, Viral immunology, Antigens, Viral metabolism, Cell Line, Cells, Cultured, DNA, Viral, Hepatocytes drug effects, Humans, Immunity, Innate, Immunologic Factors pharmacology, RNA, Viral, Virus Replication drug effects, Antiviral Agents pharmacology, Cytokines pharmacology, Hepatitis B virus drug effects, Hepatitis B virus physiology, Hepatocytes virology, Inflammation Mediators pharmacology, Interferons pharmacology
- Abstract
In HBV-infected patients, therapies with nucleoside analogues or IFNα remain ineffective in eradicating the infection. Our aim was to re-analyze the anti-HBV activity of a large panel of IFNs and cytokines in vitro using non-transformed cultured hepatocytes infected with HBV, to identify new immune-therapeutic options. HepaRG cells and primary human hepatocytes were infected with HBV and, when infection was established, treated with various concentrations of different IFNs or inflammatory cytokines. Viral parameters were evaluated by quantifying HBV nucleic acids by qPCR and Southern Blot, and secreted HBV antigens were evaluated using ELISA. The cytokines tested were type-I IFNs, IFNγ, type-III IFNs, TNFα, IL-6, IL-1β, IL-18 as well as nucleos(t)ide analogues tenofovir and ribavirin. Cytokines and drugs, with the exception of IL-18 and ribavirin, exhibited a suppressive effect on HBV replication at least as strong as, but often stronger than, IFNα. The cytokine presenting the highest effect on HBV DNA was IL-1β, which exerted its inhibition within picomolar range. Importantly, we noticed differential effects on other parameters (HBV RNA, HBeAg, HBsAg) between both IFNs and inflammatory cytokines, thus suggesting different mechanisms of action. The combination of IL-1β and already used therapies, i.e. IFNα or tenofovir, demonstrated a stronger or similar anti-HBV activity. IL-1β was found to have a very potent antiviral effect against HBV in vitro. HBV was previously shown to promptly inhibit IL-1β production in Kupffer cells. Strategies aiming at unlocking this inhibition and restoring local production of IL-1β may help to further inhibit HBV replication in vivo., (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Published
- 2016
- Full Text
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469. Novel antiviral effect of lithium chloride on mammalian orthoreoviruses in vitro.
- Author
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Chen Y, Kong D, Cai G, Jiang Z, Jiao Y, Shi Y, Li H, and Wang C
- Subjects
- Animals, Cell Line, Chlorocebus aethiops, Humans, Orthoreovirus, Mammalian physiology, Reoviridae Infections virology, Vero Cells, Virus Replication drug effects, Antiviral Agents pharmacology, Lithium Chloride pharmacology, Orthoreovirus, Mammalian drug effects
- Abstract
Reovirus not only causes considerable economic loss in the swine industry of the United States and other countries, but also threatens the public health due to its zoonotic potential. According to previous reports, LiCl has antiviral activity against a number of viruses. The inhibitory effects of LiCl on reovirus life cycle in Vero cells were evaluated. The unpaired t-test and one-way ANOVA were used to analyze the differences between experimental groups. We first found that LiCl treatment significantly inhibited reovirus replication in a dose-dependent manner. Furthermore, we found that this antiviral activity of LiCl targets the early stage of viral replication. LiCl could be a potential drug against reovirus infection., (Copyright © 2016 Elsevier Ltd. All rights reserved.)
- Published
- 2016
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470. In vitro antiviral activity of Lactobacillus casei and Bifidobacterium adolescentis against rotavirus infection monitored by NSP4 protein production.
- Author
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Olaya Galán NN, Ulloa Rubiano JC, Velez Reyes FA, Fernandez Duarte KP, Salas Cárdenas SP, and Gutierrez Fernandez MF
- Subjects
- Animals, Antiviral Agents therapeutic use, Cell Line, Macaca mulatta, Probiotics therapeutic use, Rotavirus metabolism, Rotavirus Infections drug therapy, Rotavirus Infections virology, Antiviral Agents pharmacology, Bifidobacterium adolescentis metabolism, Glycoproteins metabolism, Lacticaseibacillus casei metabolism, Probiotics pharmacology, Rotavirus drug effects, Toxins, Biological metabolism, Viral Nonstructural Proteins metabolism
- Abstract
Aims: The aim of this study was to determine the antiviral activity of four probiotic metabolites (Lactobacillus and Bifidobacetrium species) against rotavirus in vitro infection monitored by the NSP4 protein production and Ca(2+) release., Methods and Results: The antiviral effect of the metabolites was performed due a comparison between a blocking model and an intracelullar model on MA104 cells, with the response of NSP4 production and Ca(2+) liberation measured by flow cytometry. Significant results were obtained with the metabolites of Lactobacillus casei, and Bifidobacterium adolescentis in the reduction of the protein production (P = 0·04 and P = 0·014) and Ca(2+) liberation (P = 0·094 and P = 0·020) in the intracellular model, which suggests a successful antiviral activity against RV infection., Conclusions: This study demonstrates that probiotic metabolites were able to interfere with the final amount of intracellular NSP4 protein and a successful Ca(2+) regulation, which suggests a new approach to the mechanism exerted by probiotics against the rotavirus infection., Significance and Impact of the Study: A novel anti-rotaviral effect exerted by probiotic metabolites monitored by the NSP4 protein during the RV in vitro infection and the effect on the Ca(2+) release is reported; suggesting a reduction on the impact of the infection by decreasing the damage of the cells preventing the electrolyte loss., (© 2016 The Society for Applied Microbiology.)
- Published
- 2016
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471. Comparison of the responses of different recombinant fish type I interferons against betanodavirus infection in grouper.
- Author
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Kuo HP, Chung CL, Hung YF, Lai YS, Chiou PP, Lu MW, and Kong ZL
- Subjects
- Administration, Oral, Animals, Escherichia coli genetics, Fish Diseases virology, Fish Proteins genetics, Fish Proteins metabolism, Injections, Intraperitoneal veterinary, Interferon Type I genetics, Interferon Type I metabolism, Organisms, Genetically Modified genetics, RNA Virus Infections prevention & control, RNA Virus Infections virology, Recombinant Proteins genetics, Recombinant Proteins metabolism, Sequence Analysis, DNA veterinary, Bass, Fish Diseases prevention & control, Fish Proteins immunology, Interferon Type I immunology, Nodaviridae physiology, RNA Virus Infections veterinary, Recombinant Proteins immunology
- Abstract
The nervous necrosis virus (NNV) is an aquatic virus that can infect more than 30 species including the grouper, which is a valuable fish species in Taiwan. NNV causes up to 90-100% mortality in the aquaculture industry. Interferons (IFNs) are a family of cytokines that stimulate the expression of numerous proteins to protect the host against viruses and possess very unique specific characteristics in fish. The cross-reactivity of heterologous IFNs on grouper cells and larvae has not been well-studied to date. To evaluate and compare the anti-NNV effect of different fish IFNs in grouper, we successfully synthesized, subcloned, expressed and purified several fish type I IFNs in the present study: grouper (gIFN), salmon (sIFN), seabass (sbIFN) and tilapia (tpIFN). The gIFN and sIFN proteins up-regulated myxovirus resistance protein (Mx) gene expression in grouper kidney (GK) cells, but similar effects were not observed for sbIFN and tpIFN. Following co- and pre-treatment with the 4 types of IFNs with NNV infection in GK cells, sIFN exhibited the strongest antiviral ability to suppress NNV gene replication (especially at 24 h) and significantly reduced the cytopathic effect (CPE) at 72 h, followed by gIFN. Unsurprisingly, sbIFN and tpIFN had no significant effect on CPE but slightly suppressed NNV gene replication. The cytotoxicity of these four fish IFNs on GK cells was also examined for the first time. In the in vivo test, we confirmed that gIFN and sIFN had a significant protective effect against NNV when administered by intraperitoneal (IP) injection and the oral route in Malabar grouper (Epinephelus malabaricus) larvae. This study compared the protective effects of IFNs from various fish species against NNV and demonstrated crosstalk between sIFN and grouper cells for the first time. These results provide information concerning the efficacy of fish IFNs for possible therapeutic applications., (Copyright © 2015 Elsevier Ltd. All rights reserved.)
- Published
- 2016
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472. Spiromastilactones: A new class of influenza virus inhibitors from deep-sea fungus.
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Niu S, Si L, Liu D, Zhou A, Zhang Z, Shao Z, Wang S, Zhang L, Zhou D, and Lin W
- Subjects
- Animals, Antiviral Agents chemistry, Antiviral Agents isolation & purification, Benzofurans chemistry, Benzofurans isolation & purification, Dogs, Dose-Response Relationship, Drug, Lactones chemistry, Lactones isolation & purification, Madin Darby Canine Kidney Cells, Microbial Sensitivity Tests, Structure-Activity Relationship, Antiviral Agents pharmacology, Aquatic Organisms chemistry, Benzofurans pharmacology, Influenza A virus drug effects, Lactones pharmacology, Onygenales chemistry
- Abstract
A new class of phenolic lactones with trivial names of spiromastilactones A-M (1-13) was isolated from a deep-sea derived Spiromastix sp. fungus. Their structures featured by various chlorination at aromatic rings were determined on the basis of extensive spectroscopic analyses. An antiviral assay revealed that most of the tested compounds exert inhibitory activity against WSN influenza virus with low cytotoxicity, while the structure-activity relationships were discussed. Spiromastilactone D (4), a 5'-chloro-2'-methoxy substituted analogue, displayed the most potent to inhibit a panel of influenza A and B viruses in addition to drug-resistant clinical isolates. Mechanistic investigation resulted in that compound 4 bonded to hemagglutinin protein (HA), potentially at the spherical head, and disrupted the HA-sialic acid receptor interaction, that is essential for the attachment and entry of all influenza viruses. In addition, compound 4 also showed inhibitory effect toward viral genome replication via targeting viral RNP complex. The synergistic effects of 4 on both viral entry and replication assumed it to be a promising lead for the development of a new influenza inhibitor., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)
- Published
- 2016
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473. The preventive and therapeutic potential of natural polyphenols on influenza.
- Author
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Bahramsoltani R, Sodagari HR, Farzaei MH, Abdolghaffari AH, Gooshe M, and Rezaei N
- Subjects
- Animals, Antiviral Agents chemistry, Antiviral Agents isolation & purification, Biological Products chemistry, Biological Products isolation & purification, Hemagglutination, Viral drug effects, Humans, Influenza, Human prevention & control, Influenza, Human virology, Orthomyxoviridae pathogenicity, Orthomyxoviridae physiology, Plant Extracts chemistry, Plants, Medicinal chemistry, Polyphenols chemistry, Polyphenols isolation & purification, Virus Internalization drug effects, Virus Replication drug effects, Antiviral Agents pharmacology, Biological Products pharmacology, Influenza, Human drug therapy, Orthomyxoviridae drug effects, Phytotherapy methods, Polyphenols pharmacology
- Abstract
Influenza virus belongs to orthomyxoviridae family. This virus is a major public health problems, with high rates of morbidity and mortality. Despite a wide range of pharmacotherapeutic choices inhibiting specific sequences of pathological process of influenza, developing more effective therapeutic options is an immediate challenge. In this paper, a comprehensively review of natural polyphenolic products used worldwide for the management of influenza infection is presented. Cellular and molecular mechanisms of the natural polyphenols on influenza infection including suppressing virus replication cycle, viral hemagglutination, viral adhesion and penetration into the host cells, also intracellular transductional signaling pathways have been discussed in detail. Based on cellular, animal, and human evidence obtained from several studies, the current paper demonstrates that natural polyphenolic compounds possess potential effects on both prevention and treatment of influenza, which can be used as adjuvant therapy with conventional chemical drugs for the management of influenza and its complications.
- Published
- 2016
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474. Interferon-mediated antiviral activities of Angelica tenuissima Nakai and its active components.
- Author
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Weeratunga P, Uddin MB, Kim MS, Lee BH, Kim TH, Yoon JE, Ma JY, Kim H, and Lee JS
- Subjects
- Animals, Bronchoalveolar Lavage Fluid immunology, Cell Line, Coumaric Acids pharmacology, Cytokines metabolism, Enterovirus drug effects, Enterovirus physiology, Humans, Influenza A virus drug effects, Influenza A virus physiology, Mice, Mice, Inbred BALB C, Simplexvirus drug effects, Simplexvirus physiology, Vesiculovirus drug effects, Vesiculovirus physiology, Virus Replication drug effects, Angelica, Antiviral Agents pharmacology, Interferon-beta metabolism, Interferons metabolism, Orthomyxoviridae Infections prevention & control, Plant Extracts pharmacology
- Abstract
Angelica tenuissima Nakai is a widely used commodity in traditional medicine. Nevertheless, no study has been conducted on the antiviral and immune-modulatory properties of an aqueous extract of Angelica tenuissima Nakai. In the present study, we evaluated the antiviral activities and the mechanism of action of an aqueous extract of Angelica tenuissima Nakai both in vitro and in vivo. In vitro, an effective dose of Angelica tenuissima Nakai markedly inhibited the replication of Influenza A virus (PR8), Vesicular stomatitis virus (VSV), Herpes simplex virus (HSV), Coxsackie virus, and Enterovirus (EV-71) on epithelial (HEK293T/HeLa) and immune (RAW264.7) cells. Such inhibition can be described by the induction of the antiviral state in cells by antiviral, IFNrelated gene induction and secretion of IFNs and pro-inflammatory cytokines. In vivo, Angelica tenuissima Nakai treated BALB/c mice displayed higher survivability and lower lung viral titers when challenged with lethal doses of highly pathogenic influenza A subtypes (H1N1, H5N2, H7N3, and H9N2). We also found that Angelica tenuissima Nakai can induce the secretion of IL-6, IFN-λ, and local IgA in bronchoalveolar lavage fluid (BALF) of Angelica tenuissima Nakai treated mice, which correlating with the observed prophylactic effects. In HPLC analysis, we found the presence of several compounds in the aqueous fraction and among them; we evaluated antiviral properties of ferulic acid. Therefore, an extract of Angelica tenuissima Nakai and its components, including ferulic acid, play roles as immunomodulators and may be potential candidates for novel anti-viral/anti-influenza agents.
- Published
- 2016
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475. Antiviral effect of emodin from Rheum palmatum against coxsakievirus B5 and human respiratory syncytial virus in vitro.
- Author
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Liu Z, Ma N, Zhong Y, and Yang ZQ
- Subjects
- Cell Line, Cell Line, Tumor, Enterovirus B, Human physiology, Humans, In Vitro Techniques, Respiratory Syncytial Viruses physiology, Virus Replication, Antiviral Agents pharmacology, Emodin pharmacology, Enterovirus B, Human drug effects, Respiratory Syncytial Viruses drug effects, Rheum chemistry
- Abstract
Viral infections are the major causes of morbidity and mortality in elderly people and young children throughout the world. The most common pathogens include coxsackie virus (CV) and respiratory syncytial virus (RSV). However, no antiviral agents with low toxicity and drug resistance are currently available in clinic therapy. The present study aimed to examine the antiviral activities of emodin (an ingredient of Rheum palmatum) against CVB5 and RSV infections, in an attempt to discover new antiviral agents for virus infection. The monomer emodin was extracted and isolated from Rheum palmatum. The antiviral activities of emodin on HEp-2 cells were evaluated, including virus replication inhibition, virucidal and anti-absorption effects, by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tet-razolium bromide (MTT) assay and plaque reduction assay (PRA). The kinetics of virus inhibition by emodin in a period of 14 h was further determined by plaque assay and quantitative real time PCR (qPCR). Cytokine (IFN-γ, TNF-α) mRNA expressions after emodin treatment (7.5, 15, 30 μmol/L) were also assessed by qPCR post-infection. The results showed that emodin had potent inhibitory activities against CVB5 and RSV, with the 50% effective concentration (EC50) ranging from 13.06 to 14.27 μmol/L and selectivity index (SI) being 5.38-6.41 μmol/L. However, emodin couldn't directly inactivate the viruses or block their absorption to cells. It acted as a biological synthesis inhibitor against CVB4 and RSV in a concentration- and time-dependent manner, especially during the first 0-4 h post-infection. Moreover, emodin could decrease the mRNA expression of IFN-α but enhance TNF-γ expression significantly compared to the viral controls in vitro. Our results provide a molecular basis for development of emodin as a novel and safe antiviral agent for human enterovirus and respiratory virus infection in the clinical therapy.
- Published
- 2015
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476. Antiviral properties of caffeic acid phenethyl ester and its potential application.
- Author
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Erdemli HK, Akyol S, Armutcu F, and Akyol O
- Abstract
Caffeic acid phenethyl ester (CAPE) is found in a variety of plants and well-known the active ingredient of the honeybee propolis. CAPE showed anti-inflammatory, anticarcinogenic, antimitogenic, antiviral, and immunomodulatory properties in several studies. The beneficial effects of CAPE on different health issues attracted scientists to make more studies on CAPE. Specifically, the anti-viral effects of CAPE and its molecular mechanisms may reveal the important properties of virus-induced diseases. CAPE and its targets may have important roles to design new therapeutics and understand the molecular mechanisms of virus-related diseases. In this mini-review, we summarize the antiviral effects of CAPE under the light of medical and chemical literature.
- Published
- 2015
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477. Preventive Activity against Influenza (H1N1) Virus by Intranasally Delivered RNA-Hydrolyzing Antibody in Respiratory Epithelial Cells of Mice.
- Author
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Cho S, Youn HN, Hoang PM, Cho S, Kim KE, Kil EJ, Lee G, Cho MJ, Hong J, Byun SJ, Song CS, and Lee S
- Subjects
- Administration, Intranasal, Animals, Antiviral Agents pharmacokinetics, Hydrolysis, Mice, Inbred BALB C, RNA, Viral metabolism, Single-Chain Antibodies pharmacokinetics, Treatment Outcome, Antibodies, Catalytic administration & dosage, Antiviral Agents administration & dosage, Epithelial Cells immunology, Influenza A Virus, H1N1 Subtype immunology, Orthomyxoviridae Infections prevention & control, Ribonucleases administration & dosage, Single-Chain Antibodies administration & dosage
- Abstract
The antiviral effect of a catalytic RNA-hydrolyzing antibody, 3D8 scFv, for intranasal administration against avian influenza virus (H1N1) was described. The recombinant 3D8 scFv protein prevented BALB/c mice against H1N1 influenza virus infection by degradation of the viral RNA genome through its intrinsic RNA-hydrolyzing activity. Intranasal administration of 3D8 scFv (50 μg/day) for five days prior to infection demonstrated an antiviral activity (70% survival) against H1N1 infection. The antiviral ability of 3D8 scFv to penetrate into epithelial cells from bronchial cavity via the respiratory mucosal layer was confirmed by immunohistochemistry, qRT-PCR, and histopathological examination. The antiviral activity of 3D8 scFv against H1N1 virus infection was not due to host immune cytokines or chemokines, but rather to direct antiviral RNA-hydrolyzing activity of 3D8 scFv against the viral RNA genome. Taken together, our results suggest that the RNase activity of 3D8 scFv, coupled with its ability to penetrate epithelial cells through the respiratory mucosal layer, directly prevents H1N1 virus infection in a mouse model system.
- Published
- 2015
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478. Strategies for ribavirin prodrugs and delivery systems for reducing the side-effect hemolysis and enhancing their therapeutic effect.
- Author
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Guo H, Sun S, Yang Z, Tang X, and Wang Y
- Subjects
- Animals, Hemolysis drug effects, Humans, Antiviral Agents administration & dosage, Antiviral Agents chemistry, Drug Delivery Systems, Prodrugs administration & dosage, Prodrugs chemistry, Ribavirin administration & dosage, Ribavirin chemistry
- Abstract
Ribavirin is a nucleoside which is used as an antiviral agent against both RNA and DNA viruses. However, accumulation in erythrocytes causes hemolysis which limits its usefulness. To minimize ribavirin-induced hemolysis and increase its antiviral effect, considerable efforts have been made involving chemical prodrugs and various formulations. Combination with macromolecules to achieve better targeting and increased uptake is one of the most promising strategies. In addition, decreasing the association with RBCs through prodrugs and delivery systems is considered. This review summarizes prodrugs and delivery systems for ribavirin and, at the same time examines these different strategies. Moreover, a novel design of prodrug is proposed for further study., (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Published
- 2015
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479. Synthesis and anti-hepatitis B virus activity of C4 amide-substituted isosteviol derivatives.
- Author
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Huang TJ, Yang CL, Kuo YC, Chang YC, Yang LM, Chou BH, and Lin SJ
- Subjects
- Amides chemical synthesis, Amides chemistry, Amides pharmacology, Antiviral Agents chemical synthesis, Cell Line, DNA Replication drug effects, DNA, Viral genetics, Diterpenes, Kaurane chemical synthesis, Hepatitis B drug therapy, Hepatitis B metabolism, Hepatitis B virology, Hepatitis B Surface Antigens metabolism, Hepatitis B e Antigens metabolism, Hepatitis B virus genetics, Hepatitis B virus metabolism, Humans, NF-kappa B metabolism, Antiviral Agents chemistry, Antiviral Agents pharmacology, Diterpenes, Kaurane chemistry, Diterpenes, Kaurane pharmacology, Hepatitis B virus drug effects
- Abstract
A series of novel isosteviol derivatives having C4-amide substituents were synthesized in order to test for antiviral effects against the hepatitis B virus (HBV) in vitro. Among them, IN-4 [N-(propylcarbonyl)-4α-amino-19-nor-ent-16-ketobeyeran] (5) exhibited inhibitory activity against secretion of HBsAg and HBeAg as well as inhibition of HBV DNA replication. Therefore, the mechanism of its antiviral activity was further analyzed using HBV-transfected Huh7 cells. Exposure to IN-4 produced minimal inhibitory effects on viral precore/pregenomic RNA expression. However, expression levels of the 2.4/2.1-kb preS/major S RNA of the viral surface gene significantly decreased, along with intracellular levels of HBV DNA. A promoter activity analysis demonstrated that IN-4 significantly inhibited viral X, S, and preS expression levels but not viral core promoter activities. In particular, IN-4 was observed to significantly inhibit HBV gene regulation by disrupting nuclear factor (NF)-κB-associated promoter activity. In addition, the nuclear expression of p65/p50 NF-κB member proteins was attenuated following IN-4 treatment, while cytoplasmic IκBα protein levels were enhanced. Meanwhile, IN-4 was observed to inhibit the binding activity of NF-κB to putative DNA elements. Furthermore, transfection of a p65 expression plasmid into Huh7 cells significantly reversed the inhibitory effect of IN-4 on HBV DNA levels, providing further evidence of the central role of NF-κB in its antiviral mechanism. It is therefore suggested that IN-4 inhibits HBV by interfering with the NF-κB signaling pathway, resulting in downregulation of viral gene expression and DNA replication., (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Published
- 2015
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480. Molecular cloning and characterizations of porcine SAMHD1 and its roles in replication of highly pathogenic porcine reproductive and respiratory syndrome virus.
- Author
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Yang S, Shan T, Zhou Y, Jiang Y, Tong W, Liu F, Wen F, Zhang Q, and Tong G
- Subjects
- Amino Acid Sequence, Animals, Cell Line, Cell Nucleus immunology, Cell Nucleus virology, Cytokines genetics, Cytokines immunology, DNA, Complementary genetics, DNA, Complementary immunology, Gene Expression Regulation, Host-Pathogen Interactions, Leukocytes, Mononuclear immunology, Leukocytes, Mononuclear pathology, Leukocytes, Mononuclear virology, Lung immunology, Lung pathology, Lung virology, Macrophages, Alveolar pathology, Macrophages, Alveolar virology, Molecular Sequence Data, Monomeric GTP-Binding Proteins genetics, Open Reading Frames, Phosphorylation, Porcine Reproductive and Respiratory Syndrome genetics, Porcine Reproductive and Respiratory Syndrome pathology, Porcine Reproductive and Respiratory Syndrome virology, Sequence Alignment, Sequence Homology, Amino Acid, Signal Transduction, Swine, Viral Load, Virus Replication, Cloning, Molecular, Macrophages, Alveolar immunology, Monomeric GTP-Binding Proteins immunology, Porcine Reproductive and Respiratory Syndrome immunology, Porcine respiratory and reproductive syndrome virus immunology
- Abstract
The sterile alpha motif and HD domain 1 (SAMHD1) protein is a novel innate immunity restriction factor that inhibits HIV-1 infection in myeloid cells. Here, we cloned the full-length SAMHD1 complementary DNA (cDNA) from porcine peripheral blood lymphocytes. The porcine SAMHD1 cDNA was of 3951 bp with an open reading frame of 1884 bp, encoding a polypeptide of 627 amino acids. Porcine SAMHD1 mRNA was detected in all swine tissues examined, with the higher expression in the tonsil, lung, liver, and lymph node tissues. The SAMHD1 protein was localized to the nucleus. Overexpression of SAMHD1 blocked the proliferation of HuN4, a highly pathogenic strain of porcine reproductive and respiratory syndrome virus (HP-PRRSV), in MARC-145 cells, by inhibiting the synthesis of the HuN4 complement RNA. The antiviral effects of the simian SAMHD1 protein were nearly equivalent to those of porcine SAMHD1 in the HuN4-infected MARC-145 cells. Phosphorylation analysis of SAMHD1 showed that overexpressed SAMHD1 protein was in primarily an unphosphorylated state. SAMHD1 overexpression increased the transcript abundance of IFN-stimulated genes ISG15 and ISG56. The mRNA levels of SAMHD1 and ISGs were significantly increased in porcine alveolar macrophages infected with HP-PRRSV. SAMHD1 protein level was also elevated, and the protein was not phosphorylated during infection. Collectively, our data indicate that SAMHDI inhibits HP-PRRSV proliferation through inhibiting the replication of HP-PRRSV. SAMHD1 might be the protein participating in the IFN signaling and is thus an important immunoregulatory protein in innate immunity., (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Published
- 2014
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481. The coelomic fluid of the sea urchin Tripneustes depressus shows antiviral activity against Suid herpesvirus type 1 (SHV-1) and rabies virus (RV).
- Author
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Salas-Rojas M, Galvez-Romero G, Anton-Palma B, Acevedo R, Blanco-Favela F, and Aguilar-Setién A
- Subjects
- Animals, Cell Line, Dose-Response Relationship, Drug, Neutralization Tests, Virus Replication drug effects, Herpesviridae growth & development, Proteins pharmacology, Rabies virus growth & development, Sea Urchins chemistry
- Abstract
Several studies have reported that molecules extracted from invertebrates have activity against different viruses, even against those that do not infect these organisms in their environment. One of the main mechanisms against pathogens in these organisms is the production of antimicrobial peptides. The objective of this study was to determine whether the coelomic fluid (CF) of the sea urchin Tripneustes depressus has activity against Suid herpesvirus type 1 (SHV-1) and/or rabies virus (RV). We tested the antiviral activity of CF in neutralizing assays and observed 50% inhibition against SHV-1 lytic plaque formation using 33 μg of CF, whereas 21 μg CF was sufficient to obtain more than 90% inhibition for RV. Cytotoxicity to MDBK and BHK-21 cells was found with whole CF yet was eliminated by heating at 56 or 72 °C (even when using 50 μg of heat-inactivated CF supernatant [SN or thermostable fraction]), and SN retained the antiviral effect. In both cases, the antiviral effect was direct and thermostable (SN 56 and 72 °C), and the best inhibition was observed when CF + virus was incubated prior to the addition of the cells. Therefore, the coelomic fluid of T. depressus has antiviral activity against SHV-1 and RV that is direct and stable at 72 °C. We suggest that further assays should be performed using more accurate methods to characterize new molecules with antiviral activity that may result in new drugs., (Copyright © 2013 Elsevier Ltd. All rights reserved.)
- Published
- 2014
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482. Resistance to influenza A virus infection in transformed cell lines expressing an anti-PB2 monoclonal antibody.
- Author
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Fujimoto Y, Ozaki K, Maeda M, Nishijima K, Takakuwa H, Otsuki K, Kida H, and Ono E
- Subjects
- Animals, Antibodies, Viral metabolism, Antiviral Agents metabolism, Cell Line, Transformed, Chick Embryo, Chickens, Dogs, Enzyme-Linked Immunosorbent Assay veterinary, Fluorescent Antibody Technique, Direct veterinary, Influenza A virus metabolism, Madin Darby Canine Kidney Cells, RNA, Viral genetics, RNA, Viral metabolism, RNA-Dependent RNA Polymerase metabolism, Real-Time Polymerase Chain Reaction veterinary, Viral Proteins metabolism, Antibodies, Viral genetics, Influenza A virus genetics, RNA-Dependent RNA Polymerase genetics, Viral Proteins genetics
- Abstract
The polymerase basic 2 (PB2) protein is one of four proteins that make up the influenza A virus replication complex, which is responsible for viral gene transcription and replication. To assess the antiviral potential of an anti-PB2 monoclonal antibody that inhibits RNA transcription of influenza A viruses, Mardin-Darby canine kidney (MDCK) cells were transformed with two transgenes that encode the light and heavy chains of the monoclonal antibody. The transformed cell lines expressing this monoclonal antibody displayed resistance to several subtypes of influenza A virus infection. In the transformed cell lines infected with influenza A virus, the level of viral RNA transcription was decreased and the effective nuclear transportation of the PB2 protein was also inhibited. These results demonstrate that the anti-PB2 intrabody is potentially able to interfere with the effective nuclear transportation of PB2 protein, resulting in the observed resistance to influenza A virus infection in vitro., (Copyright © 2013 Elsevier Ltd. All rights reserved.)
- Published
- 2013
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483. Evidence for Paralichthys olivaceus IFITM1 antiviral effect by impeding viral entry into target cells.
- Author
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Zhu R, Wang J, Lei XY, Gui JF, and Zhang QY
- Subjects
- Amino Acid Sequence, Animals, Antigens, Differentiation genetics, Antiviral Agents, Base Sequence, Cells, Cultured, Flounder embryology, Flounder genetics, Gene Expression Regulation immunology, Immunity, Innate, Molecular Sequence Data, Phylogeny, Promoter Regions, Genetic, Virus Replication physiology, Antigens, Differentiation metabolism, Flounder immunology, Flounder metabolism, Iridoviridae physiology, Rhabdoviridae physiology, Virus Internalization
- Abstract
Interferon-inducible transmembrane (IFITM) protein family is novel viral restriction factors with representative transmembrane structure. These proteins also exist in fish, however, their roles in the innate immune response remain unknown. Here, we report a characterization of teleost IFITM1 from flounder Paralichthys olivaceus (PoIFITM1), which exhibits conserved structure characteristic of the IFITM family but comprises a relatively longer N-terminal region. The expression and promoter activity of PoIFITM1 are markedly induced by aquatic animal viruses: Rana grylio virus (RGV) and Scophthalmus maximus rhabdovirus (SMRV). Overexpression and siRNA-mediated knockdown demonstrate that PoIFITM1 exhibits strong antiviral effects against both DNA virus (RGV) and RNA virus (SMRV), expanding the spectrum of viruses inhibited by IFITM proteins. Further analysis shows that PoIFITM1 suppresses viral entry into host cells, confirming that the IFITM-mediated restriction is conserved from lower vertebrates to mammals. Deletion mutagenesis reveals that PoIFITM1 exerts antiviral activity by targeting to Golgi complex and the N-terminal region is required for its subcellular localization, which is not observed in other known IFITM family members. Our current data provide the first evidence that IFITM1 functions as a key effector of the innate immune to restrict virus replication in lower vertebrates, through the action of impeding viral entry., (Copyright © 2013 Elsevier Ltd. All rights reserved.)
- Published
- 2013
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484. Human 4F5 single-chain Fv antibody recognizing a conserved HA1 epitope has broad neutralizing potency against H5N1 influenza A viruses of different clades.
- Author
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Zhang X, Qi X, Zhang Q, Zeng X, Shi Z, Jin Q, Zhan F, Xu Y, Liu Z, Feng Z, and Jiao Y
- Subjects
- Animals, Antibodies, Neutralizing immunology, Binding Sites immunology, Chick Embryo virology, Epitope Mapping, Epitopes immunology, Humans, Influenza, Human prevention & control, Peptide Library, Protein Structure, Secondary, Antibodies, Viral immunology, Hemagglutinin Glycoproteins, Influenza Virus immunology, Influenza A Virus, H5N1 Subtype immunology, Influenza, Human immunology, Single-Chain Antibodies immunology
- Abstract
Influenza A viruses present a significant threat to public health worldwide. High-affinity human scFv antibodies against a conserved epitope can potentially provide immunity to diverse viruses and protect against future pandemic viruses. A library of phage-displayed human scFv containing 6.0×10(8) members was generated from lymphocytes of H5N1 virus vaccinated individuals. Using the recombinant H5N1 virus hemagglutinin ectodomain (HA1), 4F5 scFv was identified with neutralizing activity against both clade 2 and 9 H5N1 viruses. In embryonated chicken eggs, the antiviral activity of 4F5 scFv conferred a 100% survival rate and at least a 62.5% survival rate against different clades of H5N1 viruses by pre-treatment and post-treatment, respectively. 4F5 scFv belongs to the VH-3-43 family according to the IMGT database, and a peptide (76)WLLGNP(81) containing half of an α-helix in HA1 was identified as the binding pocket. The conserved binding epitope of this novel broadly neutralizing scFv may become key in the design and implementation of vaccines or RNA interference against H5N1 viruses., (Copyright © 2013 Elsevier B.V. All rights reserved.)
- Published
- 2013
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485. Antiviral activity of Chongkukjang extracts against influenza A virus in vitro and in vivo
- Author
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Bai Wei, Hee-Do Hong, Min Kang, Se-Yeoun Cha, Young-Jin Kim, Chang-Won Cho, Young Kyoung Rhee, and Hyung-Kwan Jang
- Subjects
biology ,Chongkukjang extracts ,Genistein ,lcsh:TX341-641 ,medicine.disease_cause ,antiviral effect ,Virology ,Virus ,In vitro ,influenza virus ,Microbiology ,Vaccination ,chemistry.chemical_compound ,chemistry ,In vivo ,Anthropology ,neuraminidase inhibitory activity ,Pandemic ,biology.protein ,Influenza A virus ,medicine ,Neuraminidase ,lcsh:Nutrition. Foods and food supply ,Food Science - Abstract
Background Chongkukjang is a traditional Korean fermented product prepared from soybeans and reported to have multiple biological functions, including antidiabetic, antiinflammatory, and neuroprotective effects. Influenza is a respiratory disease caused by influenza viruses and continues to be a worldwide threat with a high potential to cause pandemics. Besides vaccination, only two classes of drugs are available for antiviral treatment against these pathogens. Methods We tested the inhibitory activity of an ethyl acetate extract from Chongkukjang toward influenza A virus neuraminidase. Results All 10 compounds extracted from Chongkukjang showed neuraminidase inhibitory activity. Extracts A3 and A8, with high neuraminidase content, had the best inhibitory activities. The in vivo antiinfluenza virus activities of the ethyl acetate, A3, and A8 extracts as well as commercially available genistein were evaluated using H1N1 (A/NWS/33) to test mice survivability after virus challenge. The Chongkukjang extracts did not reduce mortality, but the A3 and A8 extracts delayed the median time to death after influenza A virus infection of mice. Conclusion Our results suggest that the Chongkukjang extracts may have potential as a therapeutic agent to treat influenza virus infection.
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486. The central interactive region of human MxA GTPase is involved in GTPase activation and interaction with viral target structures
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Georg Kochs, Sibylle Schneider-Schaulies, Otto Haller, and Felix Flohr
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Dynamins ,Myxovirus Resistance Proteins ,medicine.drug_class ,Blotting, Western ,Molecular Sequence Data ,Biophysics ,GTPase ,Plasma protein binding ,Biology ,Monoclonal antibody ,Biochemistry ,Antiviral Agents ,Epitope ,3T3 cells ,GTP Phosphohydrolases ,Mice ,Antiviral effect ,GTP-binding protein regulators ,Structural Biology ,GTP-Binding Proteins ,Genetics ,medicine ,Centrifugation, Density Gradient ,Escherichia coli ,Animals ,Humans ,Amino Acid Sequence ,Binding site ,Nucleocapsid ,Molecular Biology ,Peptide sequence ,Binding Sites ,Sequence Homology, Amino Acid ,Hydrolysis ,Antibodies, Monoclonal ,Proteins ,Cell Biology ,3T3 Cells ,MxA GTPase ,Molecular biology ,Precipitin Tests ,Dynamin superfamily ,medicine.anatomical_structure ,Protein Binding - Abstract
To define domains of the human MxA GTPase involved in GTP hydrolysis and antiviral activity, we used two monoclonal antibodies (mAb) directed against different regions of the molecule. mAb 2C12 recognizes an epitope in the central interactive region of MxA, whereas mAb M143 is directed against the N-terminal G domain. mAb 2C12 greatly stimulated MxA GTPase activity, suggesting that antibody-mediated crosslinking enhances GTP hydrolysis. In contrast, monovalent Fab fragments of 2C12 abolished GTPase activity, most likely by blocking intramolecular interactions required for GTPase activation. Interestingly, intact IgG molecules and Fab fragments of 2C12 both prevented association of MxA with viral nucleocapsids and neutralized MxA antiviral activity in vivo. mAb M143 had no effect on MxA function, indicating that this antibody binds outside functional regions. These data demonstrate that the central region recognized by 2C12 is critical for regulation of GTPase activity and viral target recognition.
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487. ПРОТИВОВИРУСНЫЙ ЭФФЕКТ ЭНДОНУКЛЕАЗЫ В КОМБИНАЦИИ С “БЕТАДИНОМ” // Ученые записки КФУ. Естественные науки 2013 том155 N3
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Зайнутдинова Эльмира Фаритовна, Рассохина Ирина Олеговна, Филимонова Мария Николаевна, Зайнутдинова Эльмира Фаритовна, Рассохина Ирина Олеговна, and Филимонова Мария Николаевна
- Abstract
Установлена возможность улучшения противовирусного эффекта при комбинировании эндонуклеазы грамотрицательных бактерий и “Повидон-йода”, обладающих собственным противовирусным эффектом. Сравнительный анализ противовирусного эффекта показал, что комбинирование препаратов почти в 10 раз сокращает время достижения результата, получаемого с каждым из препаратов по отдельности. Обнаружена прямая зависимость вирулицидного эффекта “Повидон-йода” и эндонуклеазы от содержания активного вещества и времени инкубации с фаговой суспензией и отсутствие зависимости от плотности вирусной суспензии.
488. Bovine interferon: its biology and application in veterinary medicine
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M J Lawman, H B Ohmann, and L. A. Babiuk
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Pharmacology ,Cytotoxicity, Immunologic ,Recombinant interferon ,Macrophages ,Cattle Diseases ,Bovine ,Biology ,Virology ,Article ,Immunomodulation ,Antiviral effect ,Interferon ,Virus Diseases ,Immunology ,medicine ,Animals ,Cattle ,Interferons ,Lymphocytes ,medicine.drug - Abstract
Investigations of the production and potential use of bovine interferons against viral infections have occurred since the first descriptions of interferons in other systems. The recent advent of recombinant DNA-technology has facilitated such studies and furthered our knowledge about the bovine interferon system in general. This review gives an overview of the biology, antiviral and immunomodulatory activities of bovine interferons. Areas in which the interferons are now applied or have potential application in viral diseases in cattle are described. Finally, the value of studies of the bovine interferon system with respect to comparative interferon research is discussed.
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- 1987
489. Inhibition of Replication and Expression of Human T-Cell Lymphotropic Virus Type III in Cultured Cells by Exogenous Synthetic Oligonucleotides Complementary to Viral RNA
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Zamecnik, Paul C., Goodchild, John, Taguchi, Yoshi, and Sarin, Prem S.
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- 1986
490. Mechanism of Interferon Uptake in Parental and Somatic Monkey-Mouse Hybrid Cells
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Chany, C., Gregoire, A., Vignal, M., Lemaitre-Moncuit, J., Brown, P., Besancon, F., Suarez, H., and Cassingena, R.
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- 1973
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