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در میان بیماری های مختلف ویروسی در ماهی، ویروس (VHSV) به عنوان مهم ترین عفونت ویروسی در ماهی قزل آلا شناخته شده است. در بررسی حاضر، تاثیر miR-731 بر روی آسیب دیدگی چشم یا اگزوفتالمی در ماهی قزل آلای رنگین کمان (Onchorhynchus mykiss) بررسی شده است. در این آزمایش ، ماهی های (1 ± 20) گرم برای تعیین احتمال پیشگیری بیماری VHS با miRNA در چهار گروه اصلی و سه تکرار، شاهد منفی بدون تزریق، فیزیولوژی با تزریق سالین، شاهد مثبت با تزریق VHSV و گروه آزمایشی با تزریق miRNA و سپس تزریق ویروس تقسیم بندی شدند. فعالیت کربنیک آنهیدراز (CA) نقش مهمی در کنترل و تنظیم فشار داخل چشم دارد که مقدار آن در گروه ها بررسی شد. نتایج نشان داد که تمام حیوانات در کنترل مثبت دچار اگزوفتالمی شدند، در گروه شاهد منفی، گروه فیزیولوژی و گروه آزمایشی اثری از اگزوفتالمی مشاهده نشد و تفاوت معنی داری بین میزان آنزیم کربنیک آنهیدراز در گروه شاهد مثبت با سایر گروه ها وجود داشت ( P<0.05). مطالعات بیش تری برای تایید مکانیسم دقیق مهار ویروس توسط miRNA مورد نیاز است، اما نتایج حاضر تا حدی نشان دهنده کاهش علائم بیماری در چشم توسط miRNA در ماهی قزل آلای رنگین کمان در مقابل عفونت VHSV است.کلید واژگان: سپتی سمی هموراژیک ویروسی, اگزوفتالمی, کربنیک آنهیدراز, miRNAAmong the various viral diseases in fish, viral hemorrhagic septicemia virus (VHSV) could be mentioned as the most significant viral infection which has now been identified for its worldwide devastating effects on trout. In the present investigation, the influence of the miR-731 on eye damage with exophthalmos (pop-eye) of VHSV in rainbow trout (O. mykiss) was examined. In current clinical trials, fishes (20± 1) g were examined to determine the possibility of pretreatment VHS disease by miR-731 in four main groups, including negative control without any injection, vehicle that received saline, positive control that were infected by VHSV (IP), and experimental group that were received miR-731 48 hour pre viral injection. Each main group subdivided into three subgroups. Carbonic anhydrase (CA) activity plays an important role in controlling aqueous production in the eye and in regulating intraocular pressure. The rate of carbonic anhydrase on trout eye was assessed in each group. Our results revealed that all animals in the positive control showed pop-eye, whereas in the negative control, the vehicle and the experimental groups were not observed any exophthalmos and there is significant difference between the rate of carbonic anhydrase in the positive control group and other groups. Although more studies are needed to verify the exact mechanisms of miR-731 viral inhibition pathway, present results partly proved that miR-731 pretreatment could decrease the sign of VHS disease eye damage.Keywords: Viral Hemorrhagic Septicemia, miRNA, exophtalmos, Carbonic anhydrase
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Background
The clinical outcome of anti-HIV therapy is poor due to the inherent fallouts ofanti-HIV therapy. It is further worsened due to the presence of viral reservoirs in immune cellslike the macrophages. An ideal anti-HIV therapy must reach, deliver the drug and exert itsaction inside macrophages. To address this, we developed novel cationic nanostructured lipidcarriers of efavirenz (cationic EFV-NLC).
MethodsThe developed cationic EFV NLCs were evaluated for particle size, zeta potential,encapsulation efficiency, in-vitro drug release, DSC, XRD, TEM, cytotoxicity, cellular uptakestudies and anti-HIV efficacy in a monocyte-derived macrophage cell line (THP-1).
ResultsCationic EFV-NLCs showed high encapsulation efficiency (90.54 ± 1.7%), uniformparticle size distribution (PDI 0.3-0.5 range) and high colloidal stability with positive zetapotential (+23.86 ± 0.49 mV). DSC and XRD studies confirmed the encapsulation of EFVwithin NLCs. Cytotoxicity studies (MTT assay) revealed excellent cytocompatibility (CC5013.23 ± 0.54 μg/mL). Fluorescence microscopy confirmed the efficient uptake of cationic EFVNLCs,while flow cytometry revealed time and concentration dependant uptake within THP-1cells. Cationic EFV-NLCs showed higher retention and sustained release with 2.32-fold higherpercent inhibition of HIV-1 in infected macrophages as compared to EFV solution at equimolarconcentrations. Interestingly, they demonstrated 1.23-fold superior anti-HIV efficacy over EFVloadedNLCs at equimolar concentrations.
ConclusionCationic NLCs were capable of inhibiting the viral replication at higher limitsconsistently for 6 days suggesting successful prevention of HIV-1 replication in infectedmacrophages and thus can prove to be an attractive tool for promising anti-HIV therapy.
Keywords: Anti-HIV efficacy, Efavirenz, HIV-AIDS infection, Nanostructured lipid carriers, Macrophages, Viral reservoirs -
The extract of licorice (Glycyrrhiza glabra L.) has been widely used for many centuries in the traditional Chinese medicine as native anti-allergic agent. Glycyrrhizin (GL), a triterpenoid-saponin, extracted from the roots of licorice is the most effective compound for inflammation and allergic diseases in human body. The biological and pharmacological studies revealed that GL possesses many pharmacological effects, such as anti-inflammatory, anti-viral and liver protective effects, and the biological effects, such as induction of cytokines (interferon- and IL-12), chemokines as well as extrathymic T and anti-type 2 T cells. This review describes (i) the pharmacological property of GL as an effective anti-inflammatory and anti-viral drug; (ii) the biochemical characteristics of several GL-binding proteins (gbPs) involved in the anti-inflammatory and anti-viral effects of 68GL and the GL-induced selective inhibition of the phosphorylation of these gbPs by GL-binding protein kinases in vitro; and (iii) the mechanisms involved in the GL-induced inhibition of the replication of both RNA and DNA viruses. In addition, recent reports concerning the mechanical actions involved in the anti-inflammatory and anti-viral effects of GL in vivo and in vitro and its clinical effects on chronic active liver disease and viral infection are summarized.
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Viruses are the most abundant and the most versatile pathogens which challenge the immune system and cause major threats for human health. In this review, I consider the mechanisms of viral evasion and subversion of immune system. Viruses inhibit humeral immunity in different ways which contains change of viral antigens, production of regulatory proteins of complement system and receptors of the Fc part of antibodies. Also, viruses disrupt interferon production with inhibition of infected cell signaling pathways for β interferon production. Additionally, one of the most important ways of viral evasion is inhibition and manipulation of cytokines and chemokines for example Herpsviruses and Poxviruses produce virokines and viroceptors. Some of the viruses inhibit apoptosis of infected cells to use cells for more amplification. In addition, viruses change maturation and expression of MHC1 and MHC2 molecule to hide of immune system recognition. Finally, most of the viruses have developed some strategies for evasion of immune system during their development. If we know them in detail we can combat them more successfully.Keywords: Viruses, Immune system, Evasion mechanisms
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BackgroundNowadays natural products such as pure compounds and plant extract scan provide unlimited opportunities for new antiviral drugs. Newcastle disease virus (NDV) is one of the most important viral diseases in poultry industry. Vaccination could provide protection against NDV outbreaks, but it is not sufficient because infections by NDVs have remained frequent around the world..ObjectivesThe current research aimed to study Achillea millefolium and Thymus vulgaris antiviral activity against Newcastle disease virus (NDV)..Materials And MethodsThe antiviral activity of the plants was measured by the reduction assay of viral titer, and explained by inhibition percentage (IP)..ResultsInhibition percentage was determined as 10 1.75, which indicated the ability of the extracts to reduce the viral potency by more than 56 folds..ConclusionsBoth plants were found effective against Newcastle disease virus..Keywords: Achillea millefolium, Thymus vulgaris, Newcastle Disease Virus, Antiviral Activity
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There are evidence showing a relationship between host Src kinase activation and viral (CVB3) replication, which are based on the observation that inhibition in the enzyme activity could result in inhibition of viral replication. The present study assessed the effect of Src kinase inactivation on viral replication at different stages of infection. It was observed that the Src kinase activity is necessary for the initiation of viral replication. In this study HeLa cell lines were treated with 5 and 10? M herbimycin A (Src kinase inhibitor) with a time schedule of -90, -60, -30, 0, +15, +30, +45,. .. +210 minutes. All cultures were infected with CVB3 at zero-minute (+ve sign indicates that herbimycin A was added after infection with CVB3). The reaction was terminated after 24 h, cells were then detached from petri plates with trypsin/EDTA. Viral replication was monitored using a set of specific primers and the plaque formation unit (PFU) count. In cells pretreated with herbimycin A before infection viral replication was inhibited. However addition of herbimycin A after infection did not affect viral replication.
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Highly pathogenic avian influenza H5N1 and Newcastle disease viral infections cause severe illness in chickens and vaccination is a strategic tool of controlling these diseases. Hence, this study was conducted to evaluate the efficacy of using both recombinant herpesvirus of turkey (rHVT-H5 and rHVT-F) vector vaccines at day-old, in the hatchery, under field conditions. Vaccinated chickens were challenged at 33 days of age with 100 µL containing 106 embryonated infective dose50 of either highly pathogenic avian influenza H5N1 or very virulent (velogenic) Newcastle disease viral strains through the intranasal route and monitored for 7 days for clinico-pathological changes. Tracheal and cloacal swabs and blood samples were also collected for determination of viral shedding using RT-PCR and immune responses using hemagglutination inhibition test. Absolute (100%) protection was recorded in vaccinated group against challenge with H5N1. In all time points, the challenge virus shedding was either not detected or greatly reduced in the trachea and the cloaca of vaccinated chickens compared to non-vaccinated, challenged chickens. Excretion of H5N1 challenge virus was not detected in the trachea of vaccinated birds at 3 and 5 days post-challenge and results of hemagglutination inhibition test revealed an average of 3.2 log2 titres at 5 days post-challenge. Protection achieved against challenge with very virulent Newcastle disease virus was 79%. There was 80-100% reduction in tracheal shedding at 3, 5, and 7 days post-challenge, and an average of 6.2, 6.0 and 6.4 log2 hemagglutination inhibition titres were recorded, respectively. Cloacal shedding of challenge Newcastle virus was greatly reduced in vaccinated groups compared to non-vaccinated, challenged chickens. These data support the efficacy of the combined use of rHVT-H5 and rHVT-F vector vaccines against highly pathogenic avian influenza and Newcastle disease viral infections under field conditions.Keywords: Viral shedding, Vector vaccine, Avian influenza, Newcastle disease, Humoral immune response
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BackgroundAchillea kellalensis, which is frequently used by Chaharmahal va Bakhtiarians residing in, Southwest of Iran, as a traditional herbal medicine for the treatment of acute diarrhea, has been selected to examine its antiviral activities against bovine rotavirus and cell toxicity activity in MA-104 cells..ObjectivesThe aim of this study was to evaluate the in vitro cytotoxic and anti-rotavirus properties of crude extracts of A. kellalensis..Materials And MethodsThe dried and powdered flowers of Achillea kellalensis were extracted with hot water and ethanol 50% (v/v). The cell viability and toxicity of the extracts were evaluated on MA-104 cells using four methods; trypan blue dye, NR, crystal violet and MTT assay. The in vitro anti-rotavirus properties were determined via four different assays, in order to evaluate the direct inhibition and/or the inhibition of viral replication..ResultsCytotoxicity of two A. kellalensis extracts showed different concentrations. Hydro-alcoholic extract had low CC50 at 600 µg/mL by the NR assay while the aqueous extract had high CC50 at 1000µg/mL by the crystal violet method. In the simultaneous treatment assay and post treatment assay, the extracts were able to prevent viral replication and inhibit the viral CPE on MA-104 cells at 10 TCID50, but the extracts did not exhibit direct antiviral activity on rotavirus adsorption. The effective concentration (EC50) of both extracts was observed to be 100 µg/mL..ConclusionsThese results indicate that A. kellalensis extracts exert potent anti-rotaviral activity only after viral adsorption. The two extracts from A. kellalensis showed a good selectivity index. Also these results suggest that extracts prepared from the flowers of A. kellalensis may be potential anti-rotaviral agents in vivo and be useful in veterinary medicine..Keywords: Achillea, Cell Survival, In Vitro
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The Coronavirus disease 2019 (COVID-19) virus spread from Wuhan, China, in 2019 and is spreading rapidly around the world. COVID-19 victims are almost associated with cardiovascular disease, high blood pressure, diabetes, and other underlying diseases. Concerning the high prevalence of these disorders, widespread mortality threatens global society, and its fatality rate may increase with increasing COVID-19 prevalence in countries with older populations. Therefore, evaluating patients' clinical status with severe COVID-19 infection and their medical history can help manage treatment. Currently, one of the considered treatments is angiotensin-converting enzyme 2 (ACE2) inhibition. This study investigated virus entry mechanisms through membrane receptors, their role in the pathogenesis of COVID-19 and underlying diseases, and treatment methods based on the viral entrance inhibition. According to existing studies, inhibition of ACE2 can increase oxidative stress, inflammation, fibrosis and ultimately exacerbate underlying diseases such as cardiovascular disease, kidney disease, diabetes, and hypertension in individuals with COVID-19. The ACE2 inhibition is not suitable for patients with COVID-19 with underlying diseases, but it seems that the recombinant ACE2 solution is more appropriate for inhibiting the virus in these patients if hypotension would be monitored.
Keywords: Angiotensin-converting enzyme 2, COVID-19, SARS-COV-2, Therapeutics -
زمینه و هدفبه دلیل قدرت و شیوع بالای عفونت زایی و عدم داروی مناسب ویروس ابولا طی سال های اخیر، پژوهش هایی در خصوص کشف و معرفی داروهای ضد ابولا انجام شده است. هدف از این پژوهش بررسی بیوانفورماتیکی مهار ورود و تکثیر ویروس ابولا توسط داروهای مجوزدار غیر ویروسی است.مواد و روش هااین پژوهش به روش توصیفی- تحلیلی انجام گرفت. برای انجام این بررسی بیوانفورماتیکی، در ابتدا ساختار شیمیایی ترکیبات با استفاده از نرم افزار ChemDraw Ultra10.0 ترسیم شد سپس به منظور بهینه سازی انرژی، به نرم افزار Hyperchem8 انتقال یافت. مطالعات داکینگ به وسیله نرم افزار AutoDock4.2 انجام شد و در مرحله نهایی، مورد آنالیز و تجزیه وتحلیل قرار گرفت.نتایجیافته های مطالعه حاضر نشان داد که پیوندهای درگیر در اتصال دارو با گیرنده ها، پیوند هیدروژنی، اتصالات هیدروفوبی، π-π و کاتیون-π می باشند. در میان تمام ترکیبات موردمطالعه، بهترین نتایج داکینگ مربوط به داروهای آمودیاکین، دیفنوکسیلات و کلروکینون است. در حقیقت این سه دارو با منفی ترین سطح انرژی اتصال تمایل بیشتری برای اتصال به اسیدهای آمینه جایگاه اتصال پروتئین های GP و VP40 دارند. ضعیف ترین نتایج داکینگ مربوط به دو داروی دیریترومایسین و اریترومایسین است زیرا هیدروفیلیسیته این دو دارو بسیار زیاد است. به طورکلی، وجود بخش های هیدروفوب، آمین نوع سوم و پیوندهای هیدروژنی بهینه باعث افزایش قدرت ضد ابولای داروها می شود.نتیجه گیریبر اساس نتایج به دست آمده از مطالعات بیوانفورماتیکی، تمام داروها تاثیرات مهاری خوبی را در جایگاه اتصال گیرنده ها از خود نشان می دهند و می توانند به عنوان مهارکننده های موثر ورود و تکثیر ویروس ابولا مطرح شوند.کلید واژگان: داکینگ, ویروس ابولا, drug repositioning, پروتئین ماتریس ویروسی اصلی 40, گلیکو پروتئینBackground & ObjectiveBecause of the reported high ability of virulence and the lack of appropriate drug of Ebola virus during the last decades, many investigations have been accomplished regarding discovery and the introduction of anti-Ebola drugs. The aim of this research was the bioinformatical study of entry and replication of Ebola viral inhibition by drug repurposing.Materials & MethodsIt is a descriptive-analytic study. In order to investigate the mode of interaction of the compounds with GP and VP40 binding sites, the chemical structures of all compounds were designed using ChemDraw program, then were transferred into Hyperchem software for energy minimization. Molecular docking simulation was accomplished using AutoDock 4.2 program.ResultsDocking results revealed the hydrophobic, hydrogen bond, π-π and π-cation contacts were involved in the drug-protein interactions. Among all the studied drugs, the best docking results were related to Amodiaquine and Diphenoxylate drugs displayed. Actually, this compounds had the most negative ΔGbinding that indicated suitable modes and favorable interactions with the amino acid residues at the binding site of GP and VP40. The weakest docking results were exhibited for Dirithromycin and Erythromycin drugs due to the high hydrophilic character of them. In general, the presence of hydrophobic portions, tertiary amines, and optimal hydrogen bonds increases the strength of anti-Ebola medications.ConclusionAccording to the results of the molecular docking, the entire FDA-approved drugs revealed a good inhibition effect on entry and replication Ebola viralKeywords: Docking, Ebola viral, Drug repositioning, VP40, GP
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از آنجا که گزینه «جستجوی دقیق» غیرفعال است همه کلمات به تنهایی جستجو و سپس با الگوهای استاندارد، رتبهای بر حسب کلمات مورد نظر شما به هر نتیجه اختصاص داده شدهاست.
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* ممکن است برخی از فیلترهای زیر دربردارنده هیچ نتیجهای نباشند.
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