scholarly journals Antiviral effect of a nucleic acid hydrolyzing scFv against oseltamivir resistant influenza A virus

2021 ◽  
Author(s):  
Yongjun Lee ◽  
Dongjun Kim ◽  
Taehyun Kim ◽  
Yeonsu Oh ◽  
Won-Keun Kim ◽  
...  
Keyword(s):  
Influenza A ◽  
Antiviral Effect ◽  
Mice Model ◽  
Single Chain ◽  
Cell Penetration ◽  
Innovative Strategy ◽  
Wide Range ◽  
Culture Models ◽  
3D8 Scfv

AbstractInfluenza viral genome is frequently mutated due to antigenic shift and drift, and therefore the existing antiviral drugs have been suffered from low efficacy against the viruses. Here we report an innovative strategy for treating influenza Type A (IAV) infection by 3D8 single chain variable fragment (scFv) showing intrinsic viral RNA hydrolyzing activity, cell penetration activity and the epidermal cell penetration ability. In this study, we first analyzed antiviral activity directed by 3D8 scFv to three different strains, two oseltamivir-sensitive (A/PuertoRico/8/1934, A/X-31) and oseltamivir-resistant (A/Korea/2785/2009pdm) using cell culture models, suggesting that 3D8 scFv reduces viral genomic RNA. Moreover, we further addressed antiviral effect to analyze clinical outcomes in in vivo mice model. Intranasal administered 3D8 scFv rescued the mice challenged by oseltamivir resistant H1N1. Consistent results are observed through IHC pathology and molecular virological analysis. Taken together, these results demonstrate that 3D8 scFv has antiviral potential against a wide range of IAV.

scholarly journals In Vitro Antiviral Activity of Favipiravir (T-705) against Drug-Resistant Influenza and 2009 A(H1N1) Viruses

2010 ◽  
Vol 54 (6) ◽  
pp. 2517-2524 ◽  
Author(s):  
Katrina Sleeman ◽  
Vasiliy P. Mishin ◽  
Varough M. Deyde ◽  
Yousuke Furuta ◽  
Alexander I. Klimov ◽  
...  
Keyword(s):  
Influenza A ◽  
Seasonal Influenza ◽  
Mdck Cells ◽  
Antiviral Effect ◽  
Plaque Formation ◽  
Influenza Viruses ◽  
New Drugs ◽  
Yield Reduction ◽  
Wide Range

ABSTRACT Favipiravir (T-705) has previously been shown to have a potent antiviral effect against influenza virus and some other RNA viruses in both cell culture and in animal models. Currently, favipiravir is undergoing clinical evaluation for the treatment of influenza A and B virus infections. In this study, favipiravir was evaluated in vitro for its ability to inhibit the replication of a representative panel of seasonal influenza viruses, the 2009 A(H1N1) strains, and animal viruses with pandemic (pdm) potential (swine triple reassortants, H2N2, H4N2, avian H7N2, and avian H5N1), including viruses which are resistant to the currently licensed anti-influenza drugs. All viruses were tested in a plaque reduction assay with MDCK cells, and a subset was also tested in both yield reduction and focus inhibition (FI) assays. For the majority of viruses tested, favipiravir significantly inhibited plaque formation at 3.2 μM (0.5 μg/ml) (50% effective concentrations [EC50s] of 0.19 to 22.48 μM and 0.03 to 3.53 μg/ml), and for all viruses, with the exception of a single dually resistant 2009 A(H1N1) virus, complete inhibition of plaque formation was seen at 3.2 μM (0.5 μg/ml). Due to the 2009 pandemic and increased drug resistance in circulating seasonal influenza viruses, there is an urgent need for new drugs which target influenza. This study demonstrates that favipiravir inhibits in vitro replication of a wide range of influenza viruses, including those resistant to currently available drugs.

scholarly journals Biobanking of human gut organoids for translational research

2021 ◽  
Author(s):  
Francesca Perrone ◽  
Matthias Zilbauer
Keyword(s):  
Translational Research ◽  
Three Dimensional ◽  
Short Review ◽  
Human Gut ◽  
Exciting Field ◽  
Wide Range ◽  
Culture Models ◽  
Scientific Expertise ◽  
Key Aspects

AbstractThe development of human organoid culture models has led to unprecedented opportunities to generate self-organizing, three-dimensional miniature organs that closely mimic in vivo conditions. The ability to expand, culture, and bank such organoids now provide researchers with the opportunity to generate next-generation living biobanks, which will substantially contribute to translational research in a wide range of areas, including drug discovery and testing, regenerative medicine as well as the development of a personalized treatment approach. However, compared to traditional tissue repositories, the generation of a living organoid biobank requires a much higher level of coordination, additional resources, and scientific expertise. In this short review, we discuss the opportunities and challenges associated with the generation of a living organoid biobank. Focusing on human intestinal organoids, we highlight some of the key aspects that need to be considered and provide an outlook for future development in this exciting field.

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 MicroRNA-7 Inhibits Rotavirus Replication by Targeting Viral NSP5 In Vivo and In Vitro

Viruses ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 209 ◽  
Author(s):  
Yan Zhou ◽  
Linlin Chen ◽  
Jing Du ◽  
Xiaoqing Hu ◽  
Yuping Xie ◽  
...  
Keyword(s):  
Rna Virus ◽  
Nonstructural Protein ◽  
Antiviral Effect ◽  
Host Cells ◽  
Mice Model ◽  
Live Attenuated Vaccine ◽  
Severe Diarrhea ◽  
Regulation Method

Rotavirus (RV) is the major causes of severe diarrhea in infants and young children under five years of age. There are no effective drugs for the treatment of rotavirus in addition to preventive live attenuated vaccine. Recent evidence demonstrates that microRNAs (miRNAs) can affect RNA virus replication. However, the antiviral effect of miRNAs during rotavirus replication are largely unknown. Here, we determined that miR-7 is upregulated during RV replication and that it targets the RV NSP5 (Nonstructural protein 5). Results suggested that miR-7 affected viroplasm formation and inhibited RV replication by down-regulating RV NSP5 expression. Up-regulation of miR-7 expression is a common regulation method of different G-type RV-infected host cells. Then, we further revealed the antiviral effect of miR-7 in diarrhea suckling mice model. MiR-7 is able to inhibit rotavirus replication in vitro and in vivo. These data provide that understanding the role of cellular miR-7 during rotaviral replication may help in the identification of novel therapeutic small RNA molecule drug for anti-rotavirus.

scholarly journals In Vitro Antiviral Activity of a Series of Wild Berry Fruit Extracts against Representatives of Picorna-, Orthomyxo- and Paramyxoviridae

2014 ◽  
Vol 9 (1) ◽  
pp. 1934578X1400900 ◽  
Author(s):  
Lubomira Nikolaeva-Glomb ◽  
Luchia Mukova ◽  
Nadya Nikolova ◽  
Ilian Badjakov ◽  
Ivayla Dincheva ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Antiviral Activity ◽  
Influenza A ◽  
Antiviral Effect ◽  
Influenza Virus A ◽  
Methanol Extracts ◽  
Wide Range ◽  
Berry Fruits ◽  
Wild Berries

Wild berry species are known to exhibit a wide range of pharmacological activities. They have long been traditionally applied for their antiseptic, antimicrobial, cardioprotective and antioxidant properties. The aim of the present study is to reveal the potential for selective antiviral activity of total methanol extracts, as well as that of the anthocyanins and the non-anthocyanins from the following wild berries picked in Bulgaria: strawberry ( Fragaria vesca L.) and raspberry ( Rubus idaeus L.) of the Rosaceae plant family, and bilberry ( Vaccinium myrtillis L.) and lingonberry ( Vaccinium vitis-idaea L) of the Ericaceae. The antiviral effect has been tested against viruses that are important human pathogens and for which chemotherapy and/or chemoprophylaxis is indicated, namely poliovirus type 1 (PV-1) and coxsackievirus B1 (CV-B1) from the Picornaviridae virus family, human respiratory syncytial virus A2 (HRSV-A2) from the Paramyxoviridae and influenza virus A/H3N2 of Orthomyxoviridae. Wild berry fruits are freeze-dried and ground, then total methanol extracts are prepared. Further the extracts are fractioned by solid phase extraction and the non-anthocyanin and anthocyanin fractions are eluted. The in vitro antiviral effect is examined by the virus cytopathic effect (CPE) inhibition test. The results reveal that the total extracts of all tested berry fruits inhibit the replication of CV-B1 and influenza A virus. CV-B1 is inhibited to the highest degree by both bilberry and strawberry, as well as by lingonberry total extracts, and influenza A by bilberry and strawberry extracts. Anthocyanin fractions of all wild berries strongly inhibit the replication of influenza virus A/H3N2. Given the obtained results it is concluded that wild berry species are a valuable resource of antiviral substances and the present study should serve as a basis for further detailed research on the matter.

scholarly journals Preparation of serum capped silver nanoparticles for selective killing of microbial cells sparing host cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rehana Parveen ◽  
Prasanta Kumar Maiti ◽  
Nabendu Murmu ◽  
Alokmay Datta
Keyword(s):  
Silver Nanoparticles ◽  
Mammalian Cells ◽  
Vascular Endothelial Cells ◽  
Host Cells ◽  
Mice Model ◽  
Human Liver Cell ◽  
Wide Range ◽  
Stress Dependent

AbstractFollowing access into the cell, colloidal silver nanoparticles exhibit generalized cytotoxic properties, thus appear as omnipotent microbicidal, but not suitable for systemic use unless are free of toxic effects on host cells. The AgNP-Serum-18 when prepared from silver nitrate, using dextrose as reducing and group-matched homologous serum as a stabilizing agent, selective endocytosis, and oxidative stress-dependent bio-functional damages to the host are mostly eliminated. For their bio-mimicking outer coat, there is the least possibility of internalization into host cells or liberation of excess oxidants in circulation following interaction with erythrocytes or vascular endothelial cells. The presence of infection-specific antibodies in the serum can make such nano-conjugates more selective. A potent antimicrobial action and a wide margin of safety for mammalian cells in comparison with very similar PVA-capped silver nanoparticles have been demonstrated by the in-vitro challenge of such nanoparticles on different microbes, human liver cell-line, and in-vivo study on mice model. This may open up wide-range therapeutic prospects of colloidal nanoparticles.

Microbiota-independent antiviral protection conferred by aminoglycoside antibiotics

2018 ◽  
Author(s):  
Smita Gopinath ◽  
Myoungjoo V. Kim ◽  
Tasfia Rakib ◽  
Patrick W. Wong ◽  
Michael van Zandt ◽  
...  
Keyword(s):  
Influenza A ◽  
Viral Infections ◽  
Antibiotic Use ◽  
Antiviral Effect ◽  
Aminoglycoside Antibiotics ◽  
Host Cells ◽  
Vaginal Mucosa ◽  
Herpes Simplex Viruses ◽  
The Impact

AbstractAntibiotics are widely used to treat infections in humans. However, the impact of antibiotic use on host cells is understudied. We have identified a novel antiviral effect of commonly used aminoglycoside antibiotics. We show that mucosal application of aminoglycosides increased host resistance to a broad range of viral infections including herpes simplex viruses, influenza A virus and Zika virus. Aminoglycoside treatment also reduced viral replication in primary human cells. This antiviral activity was independent of the microbiota as aminoglycoside treatment protected germ-free mice. Microarray analysis uncovered a marked upregulation of transcripts for interferon-stimulated genes (ISGs) following aminoglycoside application. ISG induction was mediated by TLR3, and required TIR-domain-containing adapter-inducing interferon-β (TRIF), signaling adaptor, and interferon regulatory factors 3 (IRF3) and IRF7, transcription factors that promote ISG expression. XCR1+ dendritic cells, which uniquely express TLR3, were recruited to the vaginal mucosa upon aminoglycoside treatment and were required for ISG induction. These results highlight an unexpected ability of aminoglycoside antibiotics to confer broad antiviral resistancein vivo.

scholarly journals Preparation of Serum Capped Silver Nanoparticles for Selective Killing of Microbial Cells Sparing Host Cells

2021 ◽  
Author(s):  
Rehana Parveen ◽  
Prasanta Kumar Maiti ◽  
Nabendu Murmu ◽  
Alokmay Datta
Keyword(s):  
Silver Nanoparticles ◽  
Mammalian Cells ◽  
Host Cells ◽  
Mice Model ◽  
Human Liver Cell ◽  
Wide Range ◽  
Margin Of Safety ◽  
Stress Dependent

Abstract Following access into cell, colloidal silver nanoparticles exhibit generalized cytotoxic properties, thus appear as omnipotent microbicidal, but not suitable for systemic use unless are free of toxic effects on host cells. The serum capped silver nanoparticles when prepared from silver nitrate, using dextrose as reducing and group-matched homologous serum as a stabilizing agent, selective endocytosis and oxidative stress dependent bio-functional damages to the host are mostly eliminated. For their bio-mimicking outer coat, there is least possibility of internalization into host-cells or liberation of excess oxidants in circulation following interaction with erythrocytes or vascμμμar endothelial cells. Presence of infection specific antibody in the serum can make such nano-conjugates more selective. A potent antimicrobial action and a wide margin of safety for mammalian cells in comparison with very similar PVA-capped silver nanoparticles have been demonstrated by in-vitro challenge of such nanoparticles on different microbes, human liver cell-line, and in-vivo study on mice model. This may open-up wide-range therapeutic prospects of colloidal nanoparticles.

scholarly journals Host Cell Restriction Factors of Paramyxoviruses and Pneumoviruses

Viruses ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1381
Author(s):  
Rubaiyea Farrukee ◽  
Malika Ait-Goughoulte ◽  
Philippa M. Saunders ◽  
Sarah L. Londrigan ◽  
Patrick C. Reading
Keyword(s):  
Host Cell ◽  
Influenza A ◽  
Restriction Factors ◽  
Influenza A Viruses ◽  
Host Restriction ◽  
Interferon Stimulated Genes ◽  
Wide Range ◽  
Promising Area

The paramyxo- and pneumovirus family includes a wide range of viruses that can cause respiratory and/or systemic infections in humans and animals. The significant disease burden of these viruses is further exacerbated by the limited therapeutics that are currently available. Host cellular proteins that can antagonize or limit virus replication are therefore a promising area of research to identify candidate molecules with the potential for host-targeted therapies. Host proteins known as host cell restriction factors are constitutively expressed and/or induced in response to virus infection and include proteins from interferon-stimulated genes (ISGs). Many ISG proteins have been identified but relatively few have been characterized in detail and most studies have focused on studying their antiviral activities against particular viruses, such as influenza A viruses and human immunodeficiency virus (HIV)-1. This review summarizes current literature regarding host cell restriction factors against paramyxo- and pneumoviruses, on which there is more limited data. Alongside discussion of known restriction factors, this review also considers viral countermeasures in overcoming host restriction, the strengths and limitations in different experimental approaches in studies reported to date, and the challenges in reconciling differences between in vitro and in vivo data. Furthermore, this review provides an outlook regarding the landscape of emerging technologies and tools available to study host cell restriction factors, as well as the suitability of these proteins as targets for broad-spectrum antiviral therapeutics.

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