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

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.

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Potential of acylated peptides to target the influenza A virus

Beilstein Journal of Organic Chemistry ◽

10.3762/bjoc.11.65 ◽

2015 ◽

Vol 11 ◽

pp. 589-595 ◽

Cited By ~ 5

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.

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Δ12-Prostaglandin J2 Is a Potent Inhibitor of Influenza A Virus Replication

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.44.1.200-204.2000 ◽

2000 ◽

Vol 44 (1) ◽

pp. 200-204 ◽

Cited By ~ 21

Author(s):

Francesca Pica ◽

Anna Teresa Palamara ◽

Antonio Rossi ◽

Alessandra De Marco ◽

Carla Amici ◽

...

Keyword(s):

Influenza Virus ◽

Heat Shock ◽

Influenza A Virus ◽

Influenza A ◽

Potent Inhibitor ◽

Influenza Virus Infection ◽

H1n1 Infection ◽

Shock Proteins

ABSTRACT 9-Deoxy-Δ9,Δ12-13,14-dihydro-prostaglandin D2 (Δ12-PGJ2), a natural cyclopentenone metabolite of prostaglandin D2, is shown to possess therapeutic efficacy against influenza A virus A/PR8/34 (H1N1) infection in vitro and in vivo. The results indicate that the antiviral activity is associated with induction of cytoprotective heat shock proteins and suggest novel strategies for treatment of influenza virus infection.

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Protective Role of Combined Polyphenols and Micronutrients against Influenza A Virus and SARS-CoV-2 Infection In Vitro

Biomedicines ◽

10.3390/biomedicines9111721 ◽

2021 ◽

Vol 9 (11) ◽

pp. 1721

Author(s):

Marta De Angelis ◽

David Della-Morte ◽

Gabriele Buttinelli ◽

Angela Di Martino ◽

Francesca Pacifici ◽

...

Keyword(s):

Influenza Virus ◽

Influenza A ◽

Viral Proteins ◽

Antiviral Effect ◽

Inhibitory Effect ◽

Protective Role ◽

Virus Infections ◽

Infected Cells ◽

Respiratory Virus Infections

Polyphenols have been widely studied for their antiviral effect against respiratory virus infections. Among these, resveratrol (RV) has been demonstrated to inhibit influenza virus replication and more recently, it has been tested together with pterostilbene against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In the present work, we evaluated the antiviral activity of polydatin, an RV precursor, and a mixture of polyphenols and other micronutrients, named A5+, against influenza virus and SARS-CoV-2 infections. To this end, we infected Vero E6 cells and analyzed the replication of both respiratory viruses in terms of viral proteins synthesis and viral titration. We demonstrated that A5+ showed a higher efficacy in inhibiting both influenza virus and SARS-CoV-2 infections compared to polydatin treatment alone. Indeed, post infection treatment significantly decreased viral proteins expression and viral release, probably by interfering with any step of virus replicative cycle. Intriguingly, A5+ treatment strongly reduced IL-6 cytokine production in influenza virus-infected cells, suggesting its potential anti-inflammatory properties during the infection. Overall, these results demonstrate the synergic and innovative antiviral efficacy of A5+ mixture, although further studies are needed to clarify the mechanisms underlying its inhibitory effect.

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Direct Evidence that the Poly(A) Tail of Influenza A Virus mRNA Is Synthesized by Reiterative Copying of a U Track in the Virion RNA Template

Journal of Virology ◽

10.1128/jvi.73.4.3473-3476.1999 ◽

1999 ◽

Vol 73 (4) ◽

pp. 3473-3476 ◽

Cited By ~ 122

Author(s):

Leo L. M. Poon ◽

David C. Pritlove ◽

Ervin Fodor ◽

George G. Brownlee

Keyword(s):

Influenza Virus ◽

Experimental Evidence ◽

Influenza A Virus ◽

Influenza A ◽

Direct Evidence ◽

Evidence Based ◽

Direct Experimental Evidence ◽

Plausible Hypothesis

ABSTRACT The poly(A) tail of influenza virus mRNA is thought to be synthesized by reiterative copying of the U track near the 5′ end of the virion RNA template. This has been widely accepted as a plausible hypothesis, but until now there has been no direct experimental evidence for it. Here, we report such direct evidence based on the fact that (i) replacing the U track with an A track directs synthesis of products with poly(U) tails, both in vitro and in vivo, and (ii) interrupting the U track abolishes polyadenylation in vitro.

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The inhibitory effect of dehydroepiandrosterone and its derivatives against influenza A virus in vitro and in vivo

Archives of Virology ◽

10.1007/s00705-016-2993-6 ◽

2016 ◽

Vol 161 (11) ◽

pp. 3061-3072 ◽

Cited By ~ 6

Author(s):

Qingyu Yang ◽

Qing Mao ◽

Manli Liu ◽

Kaimei Wang ◽

Zhaoyuan Wu ◽

...

Keyword(s):

Influenza A Virus ◽

Influenza A ◽

Inhibitory Effect

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Identification of a Novel Viral Protein Expressed from the PB2 Segment of Influenza A Virus

Journal of Virology ◽

10.1128/jvi.02175-15 ◽

2015 ◽

Vol 90 (1) ◽

pp. 444-456 ◽

Cited By ~ 41

Author(s):

Seiya Yamayoshi ◽

Mariko Watanabe ◽

Hideo Goto ◽

Yoshihiro Kawaoka

Keyword(s):

Influenza Virus ◽

Influenza A Virus ◽

Viral Protein ◽

Influenza A ◽

Viral Infections ◽

Viral Proteins ◽

Wild Type Virus ◽

Infected Cells

ABSTRACTOver the past 2 decades, several novel influenza virus proteins have been identified that modulate viral infectionsin vitroand/orin vivo. The PB2 segment, which is one of the longest influenza A virus segments, is known to encode only one viral protein, PB2. In the present study, we used reverse transcription-PCR (RT-PCR) targeting viral mRNAs transcribed from the PB2 segment to look for novel viral proteins encoded by spliced mRNAs. We identified a new viral protein, PB2-S1, encoded by a novel spliced mRNA in which the region corresponding to nucleotides 1513 to 1894 of the PB2 mRNA is deleted. PB2-S1 was detected in virus-infected cells and in cells transfected with a protein expression plasmid encoding PB2. PB2-S1 localized to mitochondria, inhibited the RIG-I-dependent interferon signaling pathway, and interfered with viral polymerase activity (dependent on its PB1-binding capability). The nucleotide sequences around the splicing donor and acceptor sites for PB2-S1 were highly conserved among pre-2009 human H1N1 viruses but not among human H1N1pdm and H3N2 viruses. PB2-S1-deficient viruses, however, showed growth kinetics in MDCK cells and virulence in mice similar to those of wild-type virus. The biological significance of PB2-S1 to the replication and pathogenicity of seasonal H1N1 influenza A viruses warrants further investigation.IMPORTANCETranscriptome analysis of cells infected with influenza A virus has improved our understanding of the host response to viral infection, because such analysis yields considerable information about bothin vitroandin vivoviral infections. However, little attention has been paid to transcriptomes derived from the viral genome. Here we focused on the splicing of mRNA expressed from the PB2 segment and identified a spliced viral mRNA encoding a novel viral protein. This result suggests that other, as yet unidentified viral proteins encoded by spliced mRNAs could be expressed in virus-infected cells. A viral transcriptome including the viral spliceosome should be evaluated to gain new insights into influenza virus infection.

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A Mutation in the HLA-B*2705-Restricted NP383-391 Epitope Affects the Human Influenza A Virus-Specific Cytotoxic T-Lymphocyte Response In Vitro

Journal of Virology ◽

10.1128/jvi.78.10.5216-5222.2004 ◽

2004 ◽

Vol 78 (10) ◽

pp. 5216-5222 ◽

Cited By ~ 51

Author(s):

E. G. M. Berkhoff ◽

A. C. M. Boon ◽

N. J. Nieuwkoop ◽

R. A. M. Fouchier ◽

K. Sintnicolaas ◽

...

Keyword(s):

T Cells ◽

Influenza Virus ◽

Influenza A Virus ◽

Influenza A ◽

Influenza A Viruses ◽

Ctl Response ◽

Influenza Virus A ◽

Ctl Epitope ◽

Ifn Γ

ABSTRACT Viruses can exploit a variety of strategies to evade immune surveillance by cytotoxic T lymphocytes (CTL), including the acquisition of mutations in or adjacent to CTL epitopes. Recently, an amino acid substitution (R384G) in an HLA-B*2705-restricted CTL epitope in the influenza A virus nucleoprotein (nucleoprotein containing residues 383 to 391 [NP383-391]; SRYWAIRTR, where R is the residue that was mutated) was associated with escape from CTL-mediated immunity. The effect of this mutation on the in vitro influenza A virus-specific CTL response was studied. To this end, two influenza A viruses, one with and one without the NP383-391 epitope, were constructed by reverse genetics and designated influenza viruses A/NL/94-384R and A/NL/94-384G, respectively. The absence of the HLA-B*2705-restricted CTL epitope in influenza virus A/NL/94-384G was confirmed by using 51Cr release assays with a T-cell clone specific for the NP383-391 epitope. In addition, peripheral blood mononuclear cells (PBMC) stimulated with influenza virus A/NL/94-384G failed to recognize HLA-B*2705-positive target cells pulsed with the original NP383-391 peptide. The proportion of virus-specific CD8+ gamma interferon (IFN-γ)-positive T cells in in vitro-stimulated PBMC was determined by intracellular IFN-γ staining after restimulation with virus-infected autologous B-lymphoblastoid cell lines and C1R cell lines expressing only HLA-B*2705. The proportion of virus-specific CD8+ T cells was lower in PBMC stimulated in vitro with influenza virus A/NL/94-384G obtained from several HLA-B*2705-positive donors than in PBMC stimulated with influenza virus A/NL/94-384R. This finding indicated that amino acid variations in CTL epitopes can affect the virus-specific CTL response and that the NP383-391 epitope is the most important HLA-B*2705-restricted epitope in the nucleoprotein of influenza A viruses.

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Oleanolic Acid Alleviates Atopic Dermatitis-like Responses In Vivo and In Vitro

International Journal of Molecular Sciences ◽

10.3390/ijms222112000 ◽

2021 ◽

Vol 22 (21) ◽

pp. 12000

Author(s):

Yun-Mi Kang ◽

Hye-Min Kim ◽

Minho Lee ◽

Hyo-Jin An

Keyword(s):

Atopic Dermatitis ◽

Oleanolic Acid ◽

Underlying Mechanism ◽

Skin Lesions ◽

Inhibitory Effect ◽

Hacat Keratinocytes ◽

Tnf Α ◽

Ifn Γ

Oleanolic acid (OA) is a pentacyclic triterpenoid, abundantly found in plants of the Oleaceae family, and is well known for its beneficial pharmacological activities. Previously, we reported the inhibitory effect of OA on mast cell-mediated allergic inflammation. In this study, we investigated the effects of OA on atopic dermatitis (AD)-like skin lesions and its underlying mechanism of action. We evaluated the inhibitory effect of OA on AD-like responses and the possible mechanisms using a 1-chloro-2,4-dinitrochlorobenzene (DNCB)-induced AD animal model and tumor necrosis factor (TNF)-α/interferon (IFN)-γ-stimulated HaCaT keratinocytes. We found that OA has anti-atopic effects, including histological alterations, on DNCB-induced AD-like lesions in mice. Moreover, it suppressed the expression of Th2 type cytokines and chemokines in the AD mouse model and TNF-α/IFN-γ-induced HaCaT keratinocytes by blocking the activation of serine-threonine kinase Akt, nuclear factor-κB, and the signal transducer and activator of transcription 1. The results demonstrate that OA inhibits AD-like symptoms and regulates the inflammatory mediators; therefore, it may be used as an effective and attractive therapeutic agent for allergic disorders, such as AD. Moreover, the findings of this study provide novel insights into the potential pharmacological targets of OA for treating AD.

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Effect of αvβ3 Blockade Against Acute Lung Injury Induced by Influenza A Virus and Its Mechanism

10.21203/rs.3.rs-545939/v1 ◽

2021 ◽

Author(s):

Wendi Yu ◽

Maoseng Zeng ◽

Jinyuan Liu ◽

Huixian Wang ◽

peiping xu

Keyword(s):

Influenza Virus ◽

Acute Lung Injury ◽

Lung Injury ◽

Protective Effect ◽

Influenza A Virus ◽

Influenza A ◽

Integrin Αvβ3 ◽

Tgf Β1

Abstract Integrin αvβ3 is a heterodimer formed by αv and β3 subunits that is expressed in pulmonary endothelial cells, alveolar epithelial cells, interstitial cells and macrophages. Integrin αvβ3 not only has a common role of integrin family molecules in inflammation and tissue fibrosis, but also mediates the adsorption and penetration of various viruses into susceptible cells. Nevertheless, there are few studies on the effect of αvβ3 on acute lung injury (ALI) induced by influenza virus and its mechanism. Here, the effects of αvβ3 blockade [Cyclo(RGDyK)] against ALI induced by influenza A virus (IAV) in vitro and in vivo and its possible mechanism were studied. A549 cells and mice were infected with influenza virus A/FM/1/47 to induce ALI in vitro and in vivo. The results showed that Cyclo(RGDyK) reduced the ALI induced by IAV, alleviated pulmonary edema, improved lung histopathological changes and alleviated the accumulation of inflammatory cells in the lung. Cyclo(RGDyK) had inhibitory effect on cells and mice infected by IAV. Cyclo(RGDyK) (150 µg/kg) showed effective antiviral activity in vivo. Cyclo(RGDyK) had 70% protective effect against IAV and effectively reduced virus titer and inflammation in lung tissue. Cyclo(RGDyK) exhibited significantly anti-inflammatory and anti-fibrotic effect on improving the pneumonia and degree of pulmonary fibrosis and reducing the levels of pulmonary fibrotic markers (LN, HA, PCIII, IV-C, TGF-β1, and α-SMA). Additionally, Cyclo(RGDyK) inhibited expression of αvβ3,TGF-β1, HIF-1α, NF-κB, and p38 MAPK in the cells and mice lung tissues. The results showed that Cyclo(RGDyK) had a protective effect on ALI in mice infected with IAV and inhibited the progress of lung inflammation and fibrosis, which may be concern with its regulation of αvβ3/TGF-β1/HIF-1α signaling pathway.

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