scholarly journals In Vitro and In Vivo Antiviral Activity of Gingerenone A on Influenza A Virus Is Mediated by Targeting Janus Kinase 2

Viruses ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 1141
Author(s):  
Jiongjiong Wang ◽  
Richard A. Prinz ◽  
Xiufan Liu ◽  
Xiulong Xu
Keyword(s):  
Antiviral Activity ◽  
Influenza A Virus ◽  
Influenza A ◽  
H5n1 Virus ◽  
Immune Cell ◽  
Janus Kinase ◽  
Virus Infections ◽  
Dual Inhibitor ◽  
Cell Functions

Janus kinase (JAK) inhibitors have been developed as novel immunomodulatory drugs and primarily used for treating rheumatoid arthritis and other inflammatory diseases. Recent studies have suggested that this category of anti-inflammatory drugs could be potentially useful for the control of inflammation “storms” in respiratory virus infections. In addition to their role in regulating immune cell functions, JAK1 and JAK2 have been recently identified as crucial cellular factors involved in influenza A virus (IAV) replication and could be potentially targeted for antiviral therapy. Gingerenone A (Gin A) is a compound derived from ginger roots and a dual inhibitor of JAK2 and p70 S6 kinase (S6K1). Our present study aimed to determine the antiviral activity of Gin A on influenza A virus (IAV) and to understand its mechanisms of action. Here, we reported that Gin A suppressed the replication of three IAV subtypes (H1N1, H5N1, H9N2) in four cell lines. IAV replication was also inhibited by Ruxolitinib (Rux), a JAK inhibitor, but not by PF-4708671, an S6K1 inhibitor. JAK2 overexpression enhanced H5N1 virus replication and attenuated Gin A-mediated antiviral activity. In vivo experiments revealed that Gin A treatment suppressed IAV replication in the lungs of H5N1 virus-infected mice, alleviated their body weight loss, and prolonged their survival. Our study suggests that Gin A restricts IAV replication by inhibiting JAK2 activity; Gin A could be potentially useful for the control of influenza virus infections.

scholarly journals Antiviral activity of Ladania067, an extract from wild black currant leaves against influenza A virus in vitro and in vivo

2014 ◽  
Vol 5 ◽  
Author(s):  
Emanuel Haasbach ◽  
Carmen Hartmayer ◽  
Alice Hettler ◽  
Alicja Sarnecka ◽  
Ulrich Wulle ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Influenza A Virus ◽  
Influenza A ◽  
Black Currant

scholarly journals Exacerbation of Influenza A Virus Disease Severity by Respiratory Syncytial Virus Co-Infection in a Mouse Model

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1630 ◽  
Author(s):  
Junu A. George ◽  
Shaikha H. AlShamsi ◽  
Maryam H. Alhammadi ◽  
Ahmed R. Alsuwaidi
Keyword(s):  
T Cells ◽  
Respiratory Syncytial Virus ◽  
Influenza A Virus ◽  
Influenza A ◽  
Immune Cell ◽  
Virus Disease ◽  
Viral Loads ◽  
Syncytial Virus

Influenza A virus (IAV) and respiratory syncytial virus (RSV) are leading causes of childhood infections. RSV and influenza are competitive in vitro. In this study, the in vivo effects of RSV and IAV co-infection were investigated. Mice were intranasally inoculated with RSV, with IAV, or with both viruses (RSV+IAV and IAV+RSV) administered sequentially, 24 h apart. On days 3 and 7 post-infection, lung tissues were processed for viral loads and immune cell populations. Lung functions were also evaluated. Mortality was observed only in the IAV+RSV group (50% of mice did not survive beyond 7 days). On day 3, the viral loads in single-infected and co-infected mice were not significantly different. However, on day 7, the IAV titer was much higher in the IAV+RSV group, and the RSV viral load was reduced. CD4 T cells were reduced in all groups on day 7 except in single-infected mice. CD8 T cells were higher in all experimental groups except the RSV-alone group. Increased airway resistance and reduced thoracic compliance were demonstrated in both co-infected groups. This model indicates that, among all the infection types we studied, infection with IAV followed by RSV is associated with the highest IAV viral loads and the most morbidity and mortality.

scholarly journals In vitro and in vivo mechanism of immunomodulatory and antiviral activity of Edible Bird's Nest (EBN) against influenza A virus (IAV) infection

2016 ◽  
Vol 185 ◽  
pp. 327-340 ◽  
Author(s):  
Amin Haghani ◽  
Parvaneh Mehrbod ◽  
Nikoo Safi ◽  
Nur Ain Aminuddin ◽  
Azadeh Bahadoran ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Influenza A Virus ◽  
Influenza A ◽  
Edible Bird’S Nest

Serum amyloid P component inhibits influenza A virus infections: in vitro and in vivo studies

2001 ◽  
Vol 52 (1) ◽  
pp. 43-53 ◽  
Author(s):  
A Horváth ◽  
I Andersen ◽  
K Junker ◽  
B Lyck Fogh-Schultz ◽  
E Holm Nielsen ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
In Vivo Studies ◽  
Virus Infections ◽  
Amyloid P Component ◽  
Serum Amyloid P ◽  
Serum Amyloid P Component ◽  
Amyloid P

scholarly journals Antiviral activity of Chongkukjang extracts against influenza A virus in vitro and in vivo

2015 ◽  
Vol 2 (2) ◽  
pp. 47-51 ◽  
Author(s):  
Bai Wei ◽  
Se-Yeoun Cha ◽  
Min Kang ◽  
Young Jin Kim ◽  
Chang-Won Cho ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Influenza A Virus ◽  
Influenza A

scholarly journals Novel Ranking System for Identifying Efficacious Anti-Influenza Virus PB2 Inhibitors

2015 ◽  
Vol 59 (10) ◽  
pp. 6007-6016 ◽  
Author(s):  
Alice W. Tsai ◽  
Colleen F. McNeil ◽  
Joshua R. Leeman ◽  
Hamilton B. Bennett ◽  
Kwame Nti-Addae ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A Virus ◽  
Influenza A ◽  
Therapeutic Agents ◽  
Influenza Viruses ◽  
Antigenic Drift ◽  
Whole Body ◽  
Infection Model ◽  
Virus Infections

ABSTRACTThrough antigenic drift and shifts, influenza virus infections continue to be an annual cause of morbidity in healthy populations and of death among elderly and at-risk patients. The emergence of highly pathogenic avian influenza viruses such as H5N1 and H7N9 and the rapid spread of the swine-origin H1N1 influenza virus in 2009 demonstrate the continued need for effective therapeutic agents for influenza. While several neuraminidase inhibitors have been developed for the treatment of influenza virus infections, these have shown a limited window for treatment initiation, and resistant variants have been noted in the population. In addition, an older class of antiviral drugs for influenza, the adamantanes, are no longer recommended for treatment due to widespread resistance. There remains a need for new influenza therapeutic agents with improved efficacy as well as an expanded window for the initiation of treatment. Azaindole compounds targeting the influenza A virus PB2 protein and demonstrating excellentin vitroandin vivoproperties have been identified. To evaluate thein vivoefficacy of these PB2 inhibitors, we utilized a mouse influenza A virus infection model. In addition to traditional endpoints, i.e., death, morbidity, and body weight loss, we measured lung function using whole-body plethysmography, and we used these data to develop a composite efficacy score that takes compound exposure into account. This model allowed the rapid identification and ranking of molecules relative to each other and to oseltamivir. The ability to identify compounds with enhanced preclinical properties provides an opportunity to develop more-effective treatments for influenza in patients.

scholarly journals Monoclonal Antibodies against the Fusion Peptide of Hemagglutinin Protect Mice from Lethal Influenza A Virus H5N1 Infection

2008 ◽  
Vol 83 (6) ◽  
pp. 2553-2562 ◽  
Author(s):  
Nayana Prabhu ◽  
Mookkan Prabakaran ◽  
Hui-Ting Ho ◽  
Sumathy Velumani ◽  
Jia Qiang ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Influenza A Virus ◽  
Influenza A ◽  
H5n1 Virus ◽  
Fusion Peptide ◽  
Host Cells ◽  
Therapeutic Effects ◽  
Virus Infections ◽  
H5n1 Influenza ◽  
Hpai H5n1

ABSTRACT The HA2 glycopolypeptide (gp) is highly conserved in all influenza A virus strains, and it is known to play a major role in the fusion of the virus with the endosomal membrane in host cells during the course of viral infection. Vaccines and therapeutics targeting this HA2 gp could induce efficient broad-spectrum immunity against influenza A virus infections. So far, there have been no studies on the possible therapeutic effects of monoclonal antibodies (MAbs), specifically against the fusion peptide of hemagglutinin (HA), upon lethal infections with highly pathogenic avian influenza (HPAI) H5N1 virus. We have identified MAb 1C9, which binds to GLFGAIAGF, a part of the fusion peptide of the HA2 gp. We evaluated the efficacy of MAb 1C9 as a therapy for influenza A virus infections. This MAb, which inhibited cell fusion in vitro when administered passively, protected 100% of mice from challenge with five 50% mouse lethal doses of HPAI H5N1 influenza A viruses from two different clades. Furthermore, it caused earlier clearance of the virus from the lung. The influenza virus load was assessed in lung samples from mice challenged after pretreatment with MAb 1C9 (24 h prior to challenge) and from mice receiving early treatment (24 h after challenge). The study shows that MAb 1C9, which is specific to the antigenically conserved fusion peptide of HA2, can contribute to the cross-clade protection of mice infected with H5N1 virus and mediate more effective recovery from infection.

scholarly journals In Vitro and In Vivo Antiviral Activity of Nylidrin by Targeting the Hemagglutinin 2-Mediated Membrane Fusion of Influenza A Virus

Viruses ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 581 ◽  
Author(s):  
Yejin Jang ◽  
Jin Soo Shin ◽  
Joo-Youn Lee ◽  
Heegwon Shin ◽  
Sang Jick Kim ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Membrane Fusion ◽  
Influenza A Virus ◽  
Influenza A ◽  
Intracellular Localization ◽  
Pharmacophore Modeling ◽  
Respiratory Pathogens ◽  
Antiviral Compound

Influenza A virus, one of the major human respiratory pathogens, is responsible for annual seasonal endemics and unpredictable periodic pandemics. Despite the clinical availability of vaccines and antivirals, the antigenic diversity and drug resistance of this virus makes it a persistent threat to public health, underlying the need for the development of novel antivirals. In a cell culture-based high-throughput screen, a β2-adrenergic receptor agonist, nylidrin, was identified as an antiviral compound against influenza A virus. The molecule was effective against multiple isolates of subtype H1N1, but had limited activity against subtype H3N2, depending on the strain. By examining the antiviral activity of its chemical analogues, we found that ifenprodil and clenbuterol also had reliable inhibitory effects against A/H1N1 strains. Field-based pharmacophore modeling with comparisons of active and inactive compounds revealed the importance of positive and negative electrostatic patterns of phenyl aminoethanol derivatives. Time-of-addition experiments and visualization of the intracellular localization of nucleoprotein NP demonstrated that an early step of the virus life cycle was suppressed by nylidrin. Ultimately, we discovered that nylidrin targets hemagglutinin 2 (HA2)-mediated membrane fusion by blocking conformational change of HA at acidic pH. In a mouse model, preincubation of a mouse-adapted influenza A virus (H1N1) with nylidrin completely blocked intranasal viral infection. The present study suggests that nylidrin could provide a core chemical skeleton for the development of a direct-acting inhibitor of influenza A virus entry.

scholarly journals In vivo antiviral activity: defective interfering virus protects better against virulent Influenza A virus than avirulent virus

2006 ◽  
Vol 87 (5) ◽  
pp. 1259-1265 ◽  
Author(s):  
Nigel J. Dimmock ◽  
Anthony C. Marriott
Keyword(s):  
Cell Culture ◽  
Antiviral Activity ◽  
Influenza A Virus ◽  
Influenza A ◽  
Infectious Virus ◽  
Progeny Virus ◽  
Protective Activity ◽  
Challenge Virus ◽  
In Trans

A defective interfering (DI) virus differs from the infectious virus from which it originated in having at least one major deletion in its genome. Such DI genomes are replicated only in cells infected in trans with homologous infectious virus and, as their name implies, they interfere with infectious virus replication and reduce the yield of progeny virus. This potent antiviral activity has been abundantly demonstrated in cell culture with many different DI animal viruses, but few in vivo examples have been reported, with the notable exception of DI Influenza A virus. A clue to this general lack of success arose recently when an anomaly was discovered in which DI Influenza A virus solidly protected mice from lethal disease caused by A/PR/8/34 (H1N1) and A/WSN/40 (H1N1) viruses, but protected only marginally from disease caused by A/Japan/305/57 (A/Jap, H2N2). The problem was not any incompatibility between the DI and infectious genomes, as A/Jap replicated the DI RNA in vivo. However, A/Jap required 300-fold more mouse infectious units to cause clinical disease than A/PR8 and it was hypothesized that it was this excess of infectivity that abrogated the protective activity of the DI virus. This conclusion was verified by varying the proportions of DI and challenge virus and showing that increasing the DI virus : infectious virus ratio in infected mice resulted in interference. Thus, counter-intuitively, DI virus is most effective against viruses that cause disease with low numbers of particles, i.e. virulent viruses.

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