1-Acyl-3-cyclooctylguanidines

1980 ◽  
Vol 45 (5) ◽  
pp. 1595-1600 ◽  
Author(s):  
Jaroslav Sluka ◽  
František Šmejkal ◽  
Zdeněk Buděšínský
Keyword(s):  
Influenza Virus ◽  
Herpes Simplex ◽  
Methyl Esters ◽  
Antiviral Effect ◽  
Influenza Virus A

On recation of cyclooctylamine with the sulfate of S-methylisothiourea cyclooctylguanidine was formed which was acylated with the methyl esters of 5-halogeno- and 3,5-dihalogeno-2-alkoxybenzoic acids. The 1-acyl-3-cyclooctylguanidine I-XVII formed were tested for their antiviral effect against the influenza virus A/NWS, A-PR8 and A2 Singapore, and further against the viruses NDV, herpes 2, vaccinia and WEE. In the in vivo test against the influenza virus A2 Singapore and herpes simplex 1-(5-bromo-2-dodecyloxybenzoyl)-3-cyclooctylguanidine is more active and less toxic than cyclooctylamine and 1-cyclooctylguanidine.

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

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

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

Effect of anaferon for children on the life cycle of influenza virus A/H1N1

2018 ◽  
pp. 87-94
Author(s):  
А.Г. Емельянова ◽  
М.В. Никифорова ◽  
Е.С. Дон ◽  
Н.Р. Махмудова ◽  
И.Н. Фалынскова ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Life Cycle ◽  
Antiviral Activity ◽  
Influenza A ◽  
Mdck Cells ◽  
Antiviral Effect ◽  
H1n1 Influenza ◽  
Dose Dependence ◽  
Influenza Virus A

Цель исследования - изучение возможного прямого влияния препарата «Анаферон детский» на жизненный цикл вируса гриппа А в процессе развития инфекции, а также дозозависимости противовирусного эффекта in vitro . Методика. Исследование противовирусной активности препарата «Анаферон детский» in vitro было проведено с использованием культуры клеток MDCK (Madin Darby canine kidney) и эталонных штаммов вируса гриппа A (H1N1) pdm09: A/California/07/09 и А/California/04/09, полученных от ВОЗ. Использовались методы оценки подавления Анафероном детским вирусной репликации (по результатам иммуноферментного анализа по определению экспрессии внутренних белков NP и M1 вируса гриппа А) и его влияние на ультраструктурные особенности морфогенеза вируса гриппа методом электронной микроскопии. В качестве положительного контроля был использован Озельтамивир карбоксилат в концентрации 10 мкМ. Для мониторинга валидности экспериментальной модели в работе использовали клетки, зараженные вирусом без добавления экспериментальных образцов (контроль вируса), а также интактные клетки (клеточный контроль). Результаты. В ходе исследования показан дозозависимый противовирусный эффект препарата «Анаферон детский» для 3 тестируемых разведений - 1/8, 1/12, 1/16. Методом электронной микроскопии показано, что применение препарата «Анаферон детский» при сравнении с контрольным образцом влияло на процесс почкования вирионов. Заключение. Впервые показана дозозависимость противовирусного действия препарата «Анаферон детский», а также подтверждена его эффективность в отношении двух штаммов вируса пандемического гриппа А/H1N1. Документировано, что применение препарата «Анаферон детский» нарушает жизненный цикл вируса гриппа А. Механизмы развития такого эффекта требуют дополнительного изучения, однако можно предположить их связь с ИФН-индуцирующими свойствами препарата «Анаферон детский», так как было показано, что в начале лечения вирусной инфекции препарат вызывает индукцию синтеза белков системы интерферонов. The aim of this study was to evaluate a possible direct effect of Anaferon for Children on the life cycle of influenza A virus during infection development and a dose response of the antiviral effect in vitro. Methods. The in vitro antiviral activity of Anaferon for Children was studied on cultured MDCK cells and reference strains of influenza virus A (H1N1) pdm09: A/California/07/09 and A/California/04/09, both from the WHO. Inhibition of viral replication by Anaferon for Children and its effect on ultrastructural features of the influenza morphogenesis were evaluated using electron microscopy. Results. The study demonstrated a dose dependence of Anaferon for Children antiviral activity for three dilutions - 1/8, 1/12, and 1/16. Anaferon for Children affected the process of virion budding as compared to placebo. Conclusion. The study showed that the anti-influenza action of Anaferon for Children was dose-dependent and confirmed that this drug was effective against two strains of pandemic A/H1N1 influenza. Furthermore, Anaferon for children disrupted one or several stages of the virus life cycle.

scholarly journals Antiherpes Effect of Dextran Sulphate Combined with Acyclovir in vitro and in vivo

1993 ◽  
Vol 4 (3) ◽  
pp. 189-191 ◽  
Author(s):  
S. N. Pancheva
Keyword(s):  
Herpes Simplex ◽  
Pseudorabies Virus ◽  
Antiviral Effect ◽  
Yield Reduction ◽  
Ocular Infection ◽  
Dextran Sulphate ◽  
Virus Shedding ◽  
Hsv 1

The combined antiviral effect of dextran sulphate (DS, MW 40000) and acyclovir (ACV) on herpes simplex virus type 1 (HSV-1) and Pseudorabies virus (PRV) in vitro and on experimental HSV-1 keratitis in rabbits, was studied. Dextran sulphate in combination with ACV results in synergistic effect, as measured by yield reduction assay and on herpes simplex keratitis in rabbits. The better therapeutic effect of the combination was proved by the decreased severity of ocular infection and the reduction of the virus shedding in tear film.

scholarly journals Potential of acylated peptides to target the influenza A virus

2015 ◽  
Vol 11 ◽  
pp. 589-595 ◽  
Author(s):  
Daniel Lauster ◽  
Damian Pawolski ◽  
Julian Storm ◽  
Kai Ludwig ◽  
Rudolf Volkmer ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A Virus ◽  
Influenza A ◽  
Antiviral Drug ◽  
Antiviral Effect ◽  
Inhibitory Effect ◽  
Order Structure ◽  
Lipid Phase ◽  
Multivalent Display

For antiviral drug design, especially in the field of influenza virus research, potent multivalent inhibitors raise high expectations for combating epidemics and pandemics. Among a large variety of covalent and non-covalent scaffold systems for a multivalent display of inhibitors, we created a simple supramolecular platform to enhance the antiviral effect of our recently developed antiviral Peptide B (PeBGF), preventing binding of influenza virus to the host cell. By conjugating the peptide with stearic acid to create a higher-order structure with a multivalent display, we could significantly enhance the inhibitory effect against the serotypes of both human pathogenic influenza virus A/Aichi/2/1968 H3N2, and avian pathogenic A/FPV/Rostock/34 H7N1 in the hemagglutination inhibition assay. Further, the inhibitory potential of stearylated PeBGF (C18-PeBGF) was investigated by infection inhibition assays, in which we achieved low micromolar inhibition constants against both viral strains. In addition, we compared C18-PeBGF to other published amphiphilic peptide inhibitors, such as the stearylated sugar receptor mimicking peptide (Matsubara et al. 2010), and the “Entry Blocker” (EB) (Jones et al. 2006), with respect to their antiviral activity against infection by Influenza A Virus (IAV) H3N2. However, while this strategy seems at a first glance promising, the native situation is quite different from our experimental model settings. First, we found a strong potential of those peptides to form large amyloid-like supramolecular assemblies. Second, in vivo, the large excess of cell surface membranes provides an unspecific target for the stearylated peptides. We show that acylated peptides insert into the lipid phase of such membranes. Eventually, our study reveals serious limitations of this type of self-assembling IAV inhibitors.

scholarly journals Pudilan xiaoyan oral liquid (PDL) inhibit the replication of influenza A virus through regulating TLR3/MyD88 signaling pathway

2022 ◽  
Author(s):  
Zheng Zhihui ◽  
Yuqian Zhang ◽  
Gang Tian ◽  
Zehua Wang ◽  
Ronghua Wang ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A Virus ◽  
Influenza A ◽  
Antiviral Effect ◽  
Inhibitory Effect ◽  
Tnf Α ◽  
Oral Liquid ◽  
Ifn Γ

Abstract Background Pudilan Xiaoyan Oral Liquid (PDL) as a famous Chinese patent medicine has been widely used for treating upper respiratory tract infection. However, the antiviral effect of PDL remain unclear. Here, the antiviral effect of in vitro and in vivo of PDL against influenza A virus were for the first time investigated. Methods The in vitro inhibitory effect of PDL on influenza A virus was investigated using MDCK cell model. The in vivo inhibitory effect on influenza virus pneumonia was evaluated with the ICR female mice (14-16 g) model infected by influenza A virus (A/FM/1/47, H1N1, mouse-adapted). Moreover, expression levels of inflammatory cytokines including TNF-α, IP10, IL-10, IL-1β, IL-6 and IFN-γ in lung tissue were measured by qRT-PCR. The potential mechanism of PDL against acute lung injury caused by influenza A virus was investigated by RT-PCR and Western blot. Results Our results indicated that in vitro PDL has a broad-spectrum inhibitory effect on different subtypes of influenza A viruses and in vivo PDL could dose-dependently prevent weight loss of mice, increase food intake and reduce mortality caused by influenza A H1N1 virus. Furthermore, PDL could markedly improve the acute lung injury caused by influenza A virus and significantly reduce the mRNA levels of inflammatory factors such as TNF-α, IP10, IL-10, IL-1β, IL-6, and IFN-γ. Mechanistic research indicated that the protective effect of PDL on viral pneumonia might be achieved by inhibiting TLR3/MyD88/IRAK4/TRAF3 signaling pathway. Conclusion PDL not only showed a good inhibitory effect on influenza A virus in vitro, but also exhibited a significant protective effect against lethal influenza virus infection in vivo. These findings provide evidence for the clinical treatment of influenza A virus infection with PDL.

scholarly journals Oseltamivir-Ribavirin Combination Therapy for Highly Pathogenic H5N1 Influenza Virus Infection in Mice

2008 ◽  
Vol 52 (11) ◽  
pp. 3889-3897 ◽  
Author(s):  
Natalia A. Ilyushina ◽  
Alan Hay ◽  
Neziha Yilmaz ◽  
Adrianus C. M. Boon ◽  
Robert G. Webster ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza Virus Infection ◽  
Antiviral Effect ◽  
Influenza Viruses ◽  
Oseltamivir Carboxylate ◽  
Highly Pathogenic ◽  
H5n1 Influenza ◽  
Pathogenic H5n1

ABSTRACT We studied the effects of a neuraminidase inhibitor (oseltamivir) and an inhibitor of influenza virus polymerases (ribavirin) against two highly pathogenic H5N1 influenza viruses. In vitro, A/Vietnam/1203/04 virus (clade 1) was highly susceptible to oseltamivir carboxylate (50% inhibitory concentration [IC50] = 0.3 nM), whereas A/Turkey/15/06 virus (clade 2.2) had reduced susceptibility (IC50 = 5.5 nM). In vivo, BALB/c mice were treated with oseltamivir (1, 10, 50, or 100 mg/kg of body weight/day), ribavirin (37.5, 55, or 75 mg/kg/day), or the combination of both drugs for 8 days, starting 4 h before virus inoculation. Monotherapy produced a dose-dependent antiviral effect against the two H5N1 viruses in vivo. Three-dimensional analysis of the drug-drug interactions revealed that oseltamivir and ribavirin interacted principally in an additive manner, with several exceptions of marginal synergy or marginal antagonism at some concentrations. The combination of ribavirin at 37.5 mg/kg/day and oseltamivir at 1 mg/kg/day and the combination of ribavirin at 37.5 mg/kg/day and oseltamivir at 10 mg/kg/day were synergistic against A/Vietnam/1203/04 and A/Turkey/15/06 viruses, respectively. These optimal oseltamivir-ribavirin combinations significantly inhibited virus replication in mouse organs, prevented the spread of H5N1 viruses beyond the respiratory tract, and abrogated the cytokine response (P < 0.01). Importantly, we observed clear differences between the efficacies of the drug combinations against two H5N1 viruses: higher doses were required for the protection of mice against A/Turkey/15/06 virus than for the protection of mice against A/Vietnam/1203/04 virus. Our preliminary results suggest that oseltamivir-ribavirin combinations can have a greater or lesser antiviral effect than monotherapy, depending on the H5N1 virus and the concentrations used.

scholarly journals Ocular Distribution, Spectrum of Activity, andIn VivoViral Neutralization of a Fully Humanized Anti-Herpes Simplex Virus IgG Fab Fragment following Topical Application

2011 ◽  
Vol 56 (3) ◽  
pp. 1390-1402 ◽  
Author(s):  
Marianne Berdugo ◽  
Inna V. Larsen ◽  
Claire Abadie ◽  
Catherine Deloche ◽  
Laura Kowalczuk ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Topical Administration ◽  
Antiviral Effect ◽  
Treated Group ◽  
Ocular Disease ◽  
Ocular Infection ◽  
Fab Fragment ◽  
Simplex Virus

ABSTRACTHerpes simplex ocular infection is a major cause of corneal blindness. Local antiviral treatments exist but are associated with corneal toxicity, and resistance has become an issue. We evaluated the biodistribution and efficacy of a humanized anti-herpes simplex virus (anti-HSV) IgG FAb fragment (AC-8; 53 kDa) following repeated topical administration. AC-8 was found in the corneal epithelium, anterior stroma, subepithelial stromal cells, and retinal glial cells, with preferential entry through the ocular limbus. AC-8 was active against 13 different strains of HSV-1, with 50% and 90% mean effective concentrations (MEC50and MEC90, respectively) ranging from 0.03 to 0.13 μg/ml, indicating broad-spectrum activity. Thein vivoefficacy of AC-8 was evaluated in a mouse model of herpes-induced ocular disease. Treatment with low-dose AC-8 (1 mg/ml) slightly reduced the ocular disease scores. A greater reduction of the disease scores was observed in the 10-mg/ml AC-8-treated group, but not as much as with trifluridine (TFT). AC-8 treatment reduced viral titers but less than trifluridine. AC-8 did not display any toxicity to the cornea or other structures in the eye. In summary, topical instillation of an anti-HSV FAb can be used on both intact and ulcerated corneas. It is well tolerated and does not alter reepithelialization. Further studies to improve the antiviral effect are needed for AC-8 to be considered for therapeutic use.

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