scholarly journals Combinatory Treatment with Oseltamivir and Itraconazole Targeting Both Virus and Host Factors in Influenza A Virus Infection

Viruses ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 703 ◽  
Author(s):  
Sebastian Schloer ◽  
Jonas Goretzko ◽  
Stephan Pleschka ◽  
Stephan Ludwig ◽  
Ursula Rescher
Keyword(s):  
Influenza Virus ◽  
Influenza A Virus ◽  
Influenza A ◽  
Interaction Analysis ◽  
Treatment Success ◽  
Combined Treatment ◽  
Antiviral Effect ◽  
Neuraminidase Inhibitor ◽  
Oseltamivir Resistance ◽  
Virus Strains

Influenza virus infections and their associated morbidity and mortality are a major threat to global health. Vaccination is an effective influenza prevention measure; however, the effectiveness is challenged by the rapid changes in the influenza virus genome leading to viral adaptation. Emerging viral resistance to the neuraminidase inhibitor oseltamivir limits the treatment of acute influenza infections. Targeting influenza virus-host interactions is a new and emerging field, and therapies based on the combination of virus- and host-directed drugs might significantly improve treatment success. We therefore assessed the combined treatment with oseltamivir and the repurposed antifungal drug itraconazole on infection of polarized broncho-epithelial Calu-3 cells with pdm09 or Panama influenza A virus strains. We detected significantly stronger antiviral activities in the combined treatment compared to monotherapy with oseltamivir, permitting lower concentrations of the drug than required for the single treatments. Bliss independence drug interaction analysis indicated that both drugs acted independently of each other. The additional antiviral effect of itraconazole might safeguard patients infected with influenza virus strains with heightened oseltamivir resistance.

scholarly journals Complete Genomic Sequences of H3N8 Equine Influenza Virus Strains Used as Vaccine Strains in Japan

2018 ◽  
Vol 6 (12) ◽  
Author(s):  
Manabu Nemoto ◽  
Takashi Yamanaka ◽  
Hiroshi Bannai ◽  
Koji Tsujimura ◽  
Hiroshi Kokado
Keyword(s):  
Influenza Virus ◽  
Influenza A Virus ◽  
Influenza A ◽  
Animal Health ◽  
Genomic Sequences ◽  
Equine Influenza Virus ◽  
Equine Influenza ◽  
World Organization ◽  
Virus Strains ◽  
Complete Genomic

ABSTRACT We sequenced the eight segments of influenza A virus strains A/equine/Ibaraki/1/2007 and A/equine/Yokohama/aq13/2010, which are strains of the Florida sublineage clades 1 and 2 of the H3N8 subtype equine influenza virus. These strains have been used as vaccine strains in Japan since 2016 in accordance with World Organization for Animal Health (OIE) recommendations.

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 Immunomic Analysis of the Repertoire of T-Cell Specificities for Influenza A Virus in Humans

2008 ◽  
Vol 82 (24) ◽  
pp. 12241-12251 ◽  
Author(s):  
Erika Assarsson ◽  
Huynh-Hoa Bui ◽  
John Sidney ◽  
Qing Zhang ◽  
Jean Glenn ◽  
...  
Keyword(s):  
Influenza Virus ◽  
T Cell ◽  
Influenza A Virus ◽  
Influenza A ◽  
T Cell Responses ◽  
Class Ii ◽  
Influenza Viruses ◽  
Class I ◽  
Cell Responses ◽  
Virus Strains

ABSTRACT Continuing antigenic drift allows influenza viruses to escape antibody-mediated recognition, and as a consequence, the vaccine currently in use needs to be altered annually. Highly conserved epitopes recognized by effector T cells may represent an alternative approach for the generation of a more universal influenza virus vaccine. Relatively few highly conserved epitopes are currently known in humans, and relatively few epitopes have been identified from proteins other than hemagglutinin and nucleoprotein. This prompted us to perform a study aimed at identifying a set of human T-cell epitopes that would provide broad coverage against different virus strains and subtypes. To provide coverage across different ethnicities, seven different HLA supertypes were considered. More than 4,000 peptides were selected from a panel of 23 influenza A virus strains based on predicted high-affinity binding to HLA class I or class II and high conservancy levels. Peripheral blood mononuclear cells from 44 healthy human blood donors were tested for reactivity against HLA-matched peptides by using gamma interferon enzyme-linked immunospot assays. Interestingly, we found that PB1 was the major target for both CD4+ and CD8+ T-cell responses. The 54 nonredundant epitopes (38 class I and 16 class II) identified herein provided high coverage among different ethnicities, were conserved in the majority of the strains analyzed, and were consistently recognized in multiple individuals. These results enable further functional studies of T-cell responses during influenza virus infection and provide a potential base for the development of a universal influenza vaccine.

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.

Influenza virus neuraminidase contributes to the dextran sulfate-dependent suppressive replication of some influenza A virus strains

2012 ◽  
Vol 96 (3) ◽  
pp. 344-352 ◽  
Author(s):  
Hiroshi Yamada ◽  
Eiko Moriishi ◽  
Ahmad M. Haredy ◽  
Nobuyuki Takenaka ◽  
Yasuko Mori ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A Virus ◽  
Influenza A ◽  
Dextran Sulfate ◽  
Influenza Virus Neuraminidase ◽  
Virus Strains

scholarly journals A multiplex real-time PCR assay for detection of oseltamivir-resistant strains of influenza virus

2014 ◽  
Vol 9 (6) ◽  
pp. 628-633
Author(s):  
Dawid Nidzworski ◽  
Joanna Dobkowska ◽  
Marcin Hołysz ◽  
Beata Gromadzka ◽  
Bogusław Szewczyk
Keyword(s):  
Real Time ◽  
Influenza A Virus ◽  
Real Time Pcr ◽  
Influenza A ◽  
Influenza Pandemic ◽  
Neuraminidase Inhibitor ◽  
Influenza Viruses ◽  
Antigenic Drift ◽  
Influenza A Viruses ◽  
Oseltamivir Resistance

AbstractInfluenza is a contagious disease of humans and animals caused by viruses belonging to the Orthomyxoviridae family. The influenza A virus genome consists of negative sense, single-stranded, segmented RNA. Influenza viruses are classified into subtypes based on two surface antigens known as hemagglutinin (H) and neuraminidase (N). The main problem with influenza A viruses infecting humans is drug resistance, which is caused by antigenic changes. A few antiviral drugs are available, but the most popular is the neuraminidase inhibitor — oseltamivir. The resistance against this drug has probably developed through antigenic drift by a point mutation in one amino acid at position 275 (H275Y). In order to prevent a possible influenza pandemic it is necessary to develop fast diagnostic tests. The aim of this project was to develop a new test for detection of influenza A virus and determination of oseltamivir resistance/sensitivity in humans. Detection and differentiation of oseltamivir resistance/sensitivity of influenza A virus was based on real-time PCR. This test contains two TaqMan probes, which work at different wavelengths. Application of techniques like multiplex real-time PCR has greatly enhanced the capability for surveillance and characterization of influenza viruses. After its potential validation, this test can be used for diagnosis before treatment.

scholarly journals The Effect of a Lipopolysaccharide from Rhodobacter capsulatus PG on Inflammation Caused by Various Influenza Strains

Acta Naturae ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 46-55
Author(s):  
S. V. Zubova ◽  
M. F. Vorovich ◽  
A. S. Gambaryan ◽  
A. A. Ishmukhametov ◽  
S. V. Grachev ◽  
...  
Keyword(s):  
Body Weight ◽  
Influenza Virus ◽  
Blood Serum ◽  
Influenza A Virus ◽  
Inflammatory Cytokines ◽  
Influenza A ◽  
Rhodobacter Capsulatus ◽  
Igg Antibodies ◽  
Anti Inflammatory ◽  
Virus Strains

The development of a specific inflammation in mice that had been infected by two influenza virus strains, A/chicken/Kurgan/5/2005 (H5N1) and A/Hamburg/2009 MA (H1N1), was studied. We investigated the effect of a non-toxic lipopolysaccharide from Rhodobacter capsulatus PG on the survival and body weight of the mice, production of IgG antibodies, and the induction of pro- and anti-inflammatory cytokines in blood serum. The administration of the R. capsulatus PG lipopolysaccharide was shown to induce interferon- synthesis, both in healthy and influenza A virus-infected mice, and to promote production of antiviral antibodies in the blood of the influenza-infected animals.

Drug generations that combat influenza A virus infection

2017 ◽  
Vol 13 (1) ◽  
pp. 1-11
Author(s):  
Gabriela Żaroffe ◽  
Jacek Leluk ◽  
Agata Żyźniewska ◽  
Rafał Filip
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Neuraminidase Inhibitor ◽  
Influenza Viruses ◽  
Respiratory Pathogens ◽  
Neuraminidase Inhibitors ◽  
Virus Infections ◽  
Oseltamivir Resistance ◽  
Infected Cells ◽  
New Generation

AbstractInfluenza viruses are significant human respiratory pathogens that cause infections and unpredictable pandemic outbreaks. M2 ion-channel protein, participating in the transmission of viral genetic materials into infected cells, is considered to be the crucial target for old-generation drugs such as rimantadine and amantadine. Neuraminidase protein, which is responsible for the replication of the influenza virus, is affected by the new generation of drugs, including oseltamivir (Tamiflu) and zanamivir (Relenza). The virus mutations that cause oseltamivir resistance are also described. This review presents the details concerning the treatment of influenza neuraminidase inhibitors against the H5N1 strain. It also describes virus mutations that cause resistance to oseltamivir and presents a new drug, peramivir, which is a neuraminidase inhibitor that was introduced against the H1N1 epidemic. This work specifies the details of the pharmacokinetics, dosing, toxicity, side effects, and efficiency of the drugs being used against influenza A virus infections.

scholarly journals Triple Combination of Oseltamivir, Amantadine, and Ribavirin Displays Synergistic Activity against Multiple Influenza Virus Strains In Vitro

2009 ◽  
Vol 53 (10) ◽  
pp. 4115-4126 ◽  
Author(s):  
Jack T. Nguyen ◽  
Justin D. Hoopes ◽  
Donald F. Smee ◽  
Mark N. Prichard ◽  
Elizabeth M. Driebe ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A Virus ◽  
Influenza A ◽  
New Caledonia ◽  
Mdck Cells ◽  
The United States ◽  
Health Concern ◽  
Synergistic Activity ◽  
Triple Combination ◽  
Virus Strains

ABSTRACT The recurring emergence of influenza virus strains that are resistant to available antiviral medications has become a global health concern, especially in light of the potential for a new influenza virus pandemic. Currently, virtually all circulating strains of influenza A virus in the United States are resistant to either of the two major classes of anti-influenza drugs (adamantanes and neuraminidase inhibitors). Thus, new therapeutic approaches that can be rapidly deployed and that will address the issue of recurring resistance should be developed. We have tested double and triple combinations of the approved anti-influenza drugs oseltamivir and amantadine together with ribavirin against three influenza virus strains using cytopathic effect inhibition assays in MDCK cells. We selected A/New Caledonia/20/99 (H1N1) and A/Sydney/05/97 (H3N2) as representatives of the wild-type versions of the predominant circulating seasonal influenza virus strains and A/Duck/MN/1525/81 (H5N1) as a representative of avian influenza virus strains. Dose-response curves were generated for all drug combinations, and the degree of drug interaction was quantified using a model that calculates the synergy (or antagonism) between the drugs in double and triple combinations. This report demonstrates that a triple combination of antivirals was highly synergistic against influenza A virus. Importantly, the synergy of the triple combination was 2- to 13-fold greater than the synergy of any double combination depending on the influenza virus subtype. These data support the investigation of a novel combination of oseltamivir, amantadine, and ribavirin as an effective treatment for both seasonal and pandemic influenza virus, allowing the efficient use of the existing drug supplies.

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