Influenza Virus Entry and Replication Inhibited by 8-Prenylnaringenin from Citrullus Lanatus Var. Citroides (Wild Watermelon)

2021 ◽  
Author(s):  
Akari Hanada ◽  
Ryosuke Morimoto ◽  
Yuka Horio ◽  
Mototada Shichiri ◽  
Ayaka Nakashima ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Antiviral Activity ◽  
Active Ingredient ◽  
Citrullus Lanatus ◽  
H1n1 Influenza ◽  
Influenza Viruses ◽  
Influenza B Virus ◽  
Influenza B ◽  
Prenylated Flavonoids ◽  
Virus Adsorption

Abstract We previously demonstrated the anti-influenza activity of Citrullus lanatus var. citroides (wild watermelon, WWM); however, the active ingredient was unknown. Here, we performed metabolomic analysis to evaluate the ingredients of WWM associated with antiviral activity. Many low-molecular-weight compounds were identified, with flavonoids accounting for 3% of all the compounds in WWM juice. Prenylated flavonoids accounted for 13% of the flavonoids. Among the ingredients, 8-prenylnaringenin exhibited the highest antiviral activity. We synthesized 8-prenylnaringenin and used liquid chromatography-mass spectrometry to quantitate the active ingredient in WWM. The antiviral activities of 8-prenylnaringenin were observed against H1N1 influenza subtypes, including oseltamivir-resistant H1N1 viruses, but not against an influenza B virus. Moreover, 8-prenylnaringenin was found to inhibit virus adsorption and late-stage virus replication, suggesting that the mechanisms of action of 8-prenylnaringenin may differ from those of amantadine and oseltamivir. This is the first report on the anti-influenza virus activity of 8-prenylnaringenin. Our results highlight the potential of WWM in developing effective prophylactic and therapeutic approaches against influenza viruses.

scholarly journals H1 Hemagglutinin Priming Provides Long-Lasting Heterosubtypic Immunity against H5N1 Challenge in the Mouse Model

mBio ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. e02090-20
Author(s):  
Juan Manuel Carreño ◽  
Shirin Strohmeier ◽  
Ericka Kirkpatrick Roubidoux ◽  
Rong Hai ◽  
Peter Palese ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Immune Responses ◽  
Natural Infection ◽  
Severe Infection ◽  
H1n1 Influenza ◽  
Influenza Viruses ◽  
Immune Memory ◽  
Influenza B Virus ◽  
Influenza B ◽  
Host Immune System

ABSTRACTInfluenza virus infections leave a signature of immune memory that influences future responses to infections with antigenically related strains. It has been hypothesized that the first exposure in life to H1N1 influenza virus imprints the host immune system, potentially resulting in protection from severe infection with H5N1 later in life through hemagglutinin (HA) stalk-specific antibodies. To study the specific role of the HA on protection against infection without interference of cellular immunity or humoral antineuraminidase immunity, we primed mice with influenza B viruses that express an H1 HA (group 1; B-H1), H3 HA (group 2; B-H3), or wild-type influenza B virus and subsequently challenged them at different time points with an H5N1 virus. Weight loss and survival monitoring showed that the B-H1-primed mice exhibited better protection against H5N1 compared to the control mice. Analysis of H5-specific serum IgG, before and 21 days after H5N1 challenge, evidenced the presence of anti-stalk H5 cross-reactive antibodies in the BH-1 group that were boosted by H5N1 infection. The increased immune responses and protection induced by priming with the B-H1 viruses lasted at least up to 1 year. Hence, a single HA priming based on natural infection induces long-lasting protective immunity against heterosubtypic strains from the same phylogenetic HA group in mice. This study gives mechanistic support to the earlier finding in humans that imprinting by H1 HA protects against H5N1 infections and that highly conserved regions on the HA, like the stalk, are involved in this phenomenon.IMPORTANCE Current studies point out that an HA-mediated immunological imprint is established early in life during the first exposure to influenza viruses, which critically shapes and biases future immune responses. However, studies in animal models are limited and the precise mechanisms of this phenomenon are under investigation. Studies that explore the effect of HA-specific immunity induced during natural infection on future exposures to heterosubtypic influenza strains are needed.

scholarly journals Haemagglutination-inhibition antibodies against influenza A and influenza B in maternal and neonatal sera

1978 ◽  
Vol 80 (1) ◽  
pp. 13-19 ◽  
Author(s):  
N. Masurel ◽  
J. I. de Bruijne ◽  
H. A. Beuningh ◽  
H. J. A. Schouten
Keyword(s):  
Influenza Virus ◽  
Maternal Age ◽  
Influenza A ◽  
Haemagglutination Inhibition ◽  
Influenza Viruses ◽  
Influenza B Virus ◽  
Influenza B ◽  
B Virus ◽  
Duration Of Pregnancy ◽  
Pregnancy And Birth

SUMMARYHaemagglutination inhibition (HI) antibodies against the influenza viruses A/Hong Kong/8/68 (H3N2) and B/Nederland/77/66 were determined in 420 paired sera from mothers and newborns (umbilical cord sera), sampled in 1970–1.A higher concentration of antibodies against influenza A virus was found more frequently in neonatal than in maternal sera. By contrast, low titres against influenza B virus were more frequently observed in neonatal than in maternal sera. Maternal age, duration of pregnancy, and birth-weight did not affect the results of the tests.It is suggested that the titre of the newborn against an epidemic influenza virus can be predicted from that of the mother. Furthermore, the maternal titre may be an indication of the susceptibility of the newborn infant to influenza infections.

Triazavirin might be the new hope to fight Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

2021 ◽  
Vol 70 (1) ◽  
pp. 18-25
Author(s):  
Malík Ivan ◽  
Čižmárik Jozef ◽  
Kováč Gustáv ◽  
Pecháčová Mária ◽  
Hudecová Lucia
Keyword(s):  
Influenza Virus ◽  
Severe Acute Respiratory Syndrome ◽  
Rift Valley Fever Virus ◽  
Encephalitis Virus ◽  
Influenza Viruses ◽  
Swine Flu ◽  
Influenza B Virus ◽  
Influenza B ◽  
Antiviral Compound ◽  
Virus Influenza

Since the beginning of the outbreak, a large number of clinical trials have been registered worldwide, and thousands of drugs have been investigated to face new health emergency of highly contagious COVID-19 caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Drug repurposing, i.e., utilizing an approved drug for a different indication, offers a time- and cost-efficient alternative for making new (relevant) therapies available to physicians and patients. Considering given strategy, many approved and investigational antiviral compounds, alone or in various relevant combinations, used in the past to fight Severe Acute Respiratory Syndrome Coronavirus-1, Middle East Respiratory Syndrome Coronavirus, Human Immunodeficiency Virus type 1, or Influenza viruses are being evaluated against the SARS-CoV-2. Triazavirin (TZV), a non-toxic broad--spectrum antiviral compound, is efficient against various strains of the Influenza A virus (Influenza Virus A, Orthomyxoviridae), i.e., swine flu (H1N1, or H3N2), avian influenza (H5N1, H5N2, H9N2, or highly pathogenic H7N3 strain), Influenza B virus (Influenza Virus B, Orthomyxoviridae), Respiratory Syncytial Virus (Orthopneumovirus, Pneumoviridae), Tick-Borne Encephalitis Virus (known as Forest-Spring Encephalitis Virus; Flavivirus, Flaviviridae), West Nile Virus (Flavivirus, Flavaviridae), Rift Valley Fever Virus (Phlebovirus, Bunyaviridae), and Herpes viruses (Simplexviruses, Herpesviridae) as well. In regard to COVID-19, the molecule probably reduced inflammatory reactions, thus limiting the damage to vital organs and reducing the need for therapeutic support, respectively. In addition, in silico computational methods indicated relatively satisfactory binding affinities of the TZV ligand to both structural (E)- and (S)-proteins, non-structural 3-chymotrypsin-like protease (3-CLpro) of SARS-CoV-2 as well as human angiotensin-I converting enzyme-2 (ACE-2). The interactions between TZV and given viral structures or the ACE-2 receptor for SARS-CoV-2 might effectively block both the entry of the pathogen into a host cell and its replication. Promising treatment patterns of COVID-19 positive patients might be also based on a suitable combination of a membrane fusion inhibitor (umifenovir, for example) with viral RNA synthesis and replication inhibitor (TZV).

scholarly journals Detection of severe acute respiratory syndrome coronavirus 2 and influenza viruses based on CRISPR-Cas12a

2020 ◽  
pp. 153537022096379
Author(s):  
Oraphan Mayuramart ◽  
Pattaraporn Nimsamer ◽  
Somruthai Rattanaburi ◽  
Naphat Chantaravisoot ◽  
Kritsada Khongnomnan ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Severe Acute Respiratory Syndrome ◽  
Influenza A ◽  
Limit Of Detection ◽  
Cross Reactivity ◽  
Influenza Viruses ◽  
Influenza B Virus ◽  
Influenza B ◽  
Influenza Virus A ◽  
B Virus

Due to the common symptoms of COVID-19, patients are similar to influenza-like illness. Therefore, the detection method would be crucial to discriminate between SARS-CoV-2 and influenza virus-infected patients. In this study, CRISPR-Cas12a-based detection was applied for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A virus, and influenza B virus which would be a practical and attractive application for screening of patients with COVID-19 and influenza in areas with limited resources. The limit of detection for SARS-CoV-2, influenza A, and influenza B detection was 10, 103, and 103 copies/reaction, respectively. Moreover, the assays yielded no cross-reactivity against other respiratory viruses. The results revealed that the detection of influenza virus and SARS-CoV-2 by using RT-RPA and CRISPR-Cas12a technology reaches 96.23% sensitivity and 100% specificity for SARS-CoV-2 detection. The sensitivity for influenza virus A and B detections was 85.07% and 94.87%, respectively. In addition, the specificity for influenza virus A and B detections was approximately 96%. In conclusion, the RT-RPA with CRISPR-Cas12a assay was an effective method for the screening of influenza viruses and SARS-CoV-2 which could be applied to detect other infectious diseases in the future.

scholarly journals Bacterial Sinusitis and Otitis Media following Influenza Virus Infection in Ferrets

2006 ◽  
Vol 74 (5) ◽  
pp. 2562-2567 ◽  
Author(s):  
Ville T. Peltola ◽  
Kelli L. Boyd ◽  
Julie L. McAuley ◽  
Jerold E. Rehg ◽  
Jonathan A. McCullers
Keyword(s):  
Influenza Virus ◽  
Otitis Media ◽  
Influenza A ◽  
Bacterial Colonization ◽  
Influenza Virus Infection ◽  
Influenza Viruses ◽  
Influenza B Virus ◽  
Influenza B ◽  
Complication Rates ◽  
Pneumococcal Infections

ABSTRACT Streptococcus pneumoniae is the leading cause of otitis media, sinusitis, and pneumonia. Many of these infections result from antecedent influenza virus infections. In this study we sought to determine whether the frequency and character of secondary pneumococcal infections differed depending on the strain of influenza virus that preceded bacterial challenge. In young ferrets infected with influenza virus and then challenged with pneumococcus, influenza viruses of any subtype increased bacterial colonization of the nasopharynx. Nine out of 10 ferrets infected with H3N2 subtype influenza A viruses developed either sinusitis or otitis media, while only 1 out of 11 ferrets infected with either an H1N1 influenza A virus or an influenza B virus did so. These data may partially explain why bacterial complication rates are higher during seasons when H3N2 viruses predominate. This animal model will be useful for further study of the mechanisms that underlie viral-bacterial synergism.

scholarly journals Impact of oseltamivir treatment on influenza A and B dynamics in human volunteers

2020 ◽  
Author(s):  
Kyla L. Hooker ◽  
Vitaly V. Ganusov
Keyword(s):  
Clinical Trials ◽  
Influenza Virus ◽  
Influenza A ◽  
Influenza Viruses ◽  
Influenza B Virus ◽  
Influenza B ◽  
Virus Shedding ◽  
Viral Shedding ◽  
Human Volunteers ◽  
The Impact

AbstractInfluenza viruses infect millions of humans every year causing an estimated 400,000 deaths globally. Due to continuous virus evolution current vaccines provide only limited protection against the flu. Several antiviral drugs are available to treat influenza infection, and one of the most most commonly used drugs is oseltamivir (Tamiflu). While the mechanism of action of oseltamivir as a neuraminidase inhibitor is well understood, the impact of oseltamivir on influenza virus dynamics in humans has been controversial. Many clinical trials with oseltamivir have been done by pharmaceutical companies such as Roche but the results of these trials until recently have been reported as summary reports or papers. Typically, such reports included median virus shedding curves for placebo and drug-treated influenza virus infected volunteers often indicating high efficacy of the early treatment. However, median shedding curves may be not accurately representing drug impact in individual volunteers. Importantly, due to public pressure clinical trials data testing oseltamivir efficacy has been recently released in the form of redacted PDF documents. We digitized and re-analyzed experimental data on influenza virus shedding in human volunteers from three previously published trials: on influenza A (1 trial) or B viruses (2 trials). Given that not all volunteers exposed to influenza viruses actually start virus shedding we found that impact of oseltamivir on the virus shedding dynamics was dependent on i) selection of volunteers that were infected with the virus, and ii) the detection limit in the measurement assay; both of these details were not well articulated in the published studies. By assuming that any viral measurement is above the limit of detection we could match previously published data on median influenza A virus (flu A study) shedding but not on influenza B virus shedding (flu B study B) in human volunteers. Additional analyses confirmed that oseltamivir had an impact on the duration of shedding and overall shedding (defined as area under the curve) but this result was varied by the trial. Interestingly, treatment had no impact on the rates at which shedding increased or declined with time in individual volunteers. Additional analyses showed that oseltamivir impacted the kinetics of the start and end of viral shedding and in about 20-40% of volunteers treatment had no impact on viral shedding duration. Our results suggest an unusual impact of oseltamivir on influenza viruses shedding kinetics and caution about the use of published median data or data from a few individuals for inferences. Furthermore, we call for the need to publish raw data from critical clinical trials that can be then independently analyzed.

scholarly journals Age Dependence and Isotype Specificity of Influenza Virus Hemagglutinin Stalk-Reactive Antibodies in Humans

mBio ◽  
2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Raffael Nachbagauer ◽  
Angela Choi ◽  
Ruvim Izikson ◽  
Manon M. Cox ◽  
Peter Palese ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Influenza Virus Infection ◽  
The Elderly ◽  
Influenza Viruses ◽  
Influenza B Virus ◽  
Enzyme Linked Immunosorbent Assay ◽  
Influenza B ◽  
Dependent Manner ◽  
Specific Antibodies

ABSTRACT Influenza remains a major global health burden. Seasonal vaccines offer protection but can be rendered less effective when the virus undergoes extensive antigenic drift. Antibodies that target the highly conserved hemagglutinin stalk can protect against drifted viruses, and vaccine constructs designed to induce such antibodies form the basis for a universal influenza virus vaccine approach. In this study, we analyzed baseline and postvaccination serum samples of children (6 to 59 months), adults (18 to 49 years), and elderly individuals (≥65 years) who participated in clinical trials with a recombinant hemagglutinin-based vaccine. We found that baseline IgG and IgA antibodies against the H1 stalk domain correlated with the ages of patients. Children generally had very low baseline titers and did not respond well to the vaccine in terms of making stalk-specific antibodies. Adults showed the highest induction of stalk-specific antibodies, but the elderly had the highest absolute antibody titers against the stalk. Importantly, the stalk antibodies measured by enzyme-linked immunosorbent assay (ELISA) showed neutralizing activity in neutralization assays and protected mice in a passive-transfer model in a stalk titer-dependent manner. Finally, we found similar patterns of stalk-specific antibodies directed against the H3 and influenza B virus hemagglutinins, albeit at lower levels than those measured against the H1 stalk. The relatively high levels of stalk-specific antibodies in the elderly patients may explain the previously reported low influenza virus infection rates in this age group. (This study has been registered at ClinicalTrials.gov under registration no. NCT00336453, NCT00539981, and NCT00395174.) IMPORTANCE The present study provides evidence that titers of broadly neutralizing hemagglutinin stalk-reactive antibodies increase with age, possibly due to repeated exposure to divergent influenza viruses. These relatively high levels of antistalk titers may be responsible for lower circulation rates of influenza viruses in older individuals. Our findings suggest that the level of antistalk antibodies is a good surrogate marker for protection against influenza virus infection. In addition, the levels of antistalk antibodies might determine the breadth of protection against different drifted strains.

Antibody Responses to Influenza B Viruses in Immunologically Unprimed Children

PEDIATRICS ◽  
1991 ◽  
Vol 88 (5) ◽  
pp. 1031-1036
Author(s):  
Roland A. Levandowski ◽  
Helen L. Regnery ◽  
Eldridge Staton ◽  
B. Gail Burgess ◽  
Michael S. Williams ◽  
...  
Keyword(s):  
Influenza Virus ◽  
High Risk ◽  
Pediatric Patients ◽  
Influenza Viruses ◽  
Influenza B Virus ◽  
Influenza B ◽  
Trivalent Influenza Vaccine ◽  
B Virus ◽  
High Risk Infants ◽  
Infants And Young Children

The cocirculation in several parts of the world of influenza viruses B/Yamagata/16/88 and B/Victoria/2/87, which are genetically and antigenically divergent, has prompted the question of whether immunization with one viral antigen is sufficient for protection against both strains. Twenty-three high-risk infants and young children were immunized with a commercial trivalent influenza vaccine containing the antigens of influenza virus B/Yamagata/16/88. When antibodies against influenza viruses B/Yamagata/16/88 and B/Victoria/2/87 were determined, increases developed uniformly to both in the sera of primed children previously exposed to influenza virus B/Victoria/2/87 by immunization or infection. Antibodies against B/Yamagata/16/88 developed in the sera of unprimed children with titers similar to those of the primed children. However, antibodies to B/ Victoria/2/87 were not detected in the sera of the unprimed children. These data suggest that children with out appropriate immunologic priming may not be protected against an infection with a B/Victoria/2/87 strain after vaccination with a B/Yamagata/16/88 strain. Immunization with more than one influenza B virus strain may be desirable in some high-risk pediatric patients if divergent influenza B viruses circulate.

scholarly journals Entry of influenza viruses into cells is inhibited by a highly specific protein kinase C inhibitor

2000 ◽  
Vol 81 (11) ◽  
pp. 2697-2705 ◽  
Author(s):  
Christiana N. Root ◽  
Elizabeth G. Wills ◽  
LaShonn L. McNair ◽  
Gary R. Whittaker
Keyword(s):  
Influenza Virus ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Influenza Virus Infection ◽  
Influenza Viruses ◽  
Influenza B Virus ◽  
Influenza B ◽  
Dependent Manner ◽  
Kinase C ◽  
Dose Dependent

Following binding to cell surface sialic acid, entry of influenza viruses into cells is mediated by endocytosis. Productive entry of influenza virus requires the low-pH environment of the late endosome for fusion and release of the virus into the cytoplasm and transport of the virus genome into the nucleus. We investigated novel mechanisms to inhibit influenza virus infection using highly specific inhibitors of protein kinase C. We found that one inhibitor, bisindolylmaleimide I, prevented replication of influenza A virus in a dose-dependent manner when added at the time of infection, but had little specific effect when added 2 h after infection had commenced. Virus yields dropped by more than 3 log units in the presence of micromolar levels of bisindolylmaleimide I. Influenza B virus replication was also inhibited by bisindolylmaleimide at micromolar concentrations. We carried out experiments to determine the point in infection that was blocked by bisindolylmaleimide I, and determined that entry of viral ribonucleoproteins (vRNPs) into the nucleus was prevented. Upon drug washout vRNP nuclear entry resumed, showing that bisindolylmaleimide I is reversible. Bisindolylmaleimide I did not affect virus binding and was apparently not acting as a weak base, because its effects were independent of the pH of the external growth medium. These experiments show that bisindolylmaleimide I blocks replication of different types of influenza virus in a dose-dependent and reversible manner, and that virus entry into the cell is inhibited.

Mechanisms of Antiviral Activity of Cistus Salviifolius Extract Against Human Respiratory Viruses

2020 ◽  
Vol 65 (7-8) ◽  
pp. 8-17
Author(s):  
Ya. L. Esaulkova ◽  
A. A. Muryleva ◽  
E. O. Sinegubova ◽  
S. V. Belyaevskaya ◽  
A. V. Garshinina ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Viral Infections ◽  
Time Window ◽  
Respiratory Viruses ◽  
Influenza Viruses ◽  
Influenza B Virus ◽  
Influenza B ◽  
High Priority Task ◽  
Causative Agents ◽  
Cistus Salviifolius

Influenza and ARVIs are the most common forms of infectious respiratory diseases in humans. In this regard, the search and development of means for the prevention and treatment of viral infections is a high priority task. The aim of this study was to assess the mechanisms of the antiviral activity of sage-leaved rock-rose extract (Cistus salviifolius) against the causative agents of influenza and ARVIs in humans. In the course of the study, it was shown that C.salviifolius extract inhibits reproduction of influenza viruses A(H1N1), A (H1N1)pdm09, A(H3N2), A(H5N2), A(H7N9) and influenza B virus. The extract showed maximum virus-inhibiting activity at the early stages of the viral cycle (0–2 hours after infection). C.salviifolius extract significantly reduced the hemagglutinating activity of the virus, and at the same time did not affect the fusogenic properties of viral hemagglutinin. Transmission electron microscopy was used to demonstrate that the cistus extract prevents the absorption of influenza virions on the surface of cells in culture. The inhibitory activity of the extract against other human respiratory viruses, parainfluenza virus and adenovirus, was also shown. The protective activity of C.salviifolius extract was demonstrated when applied intranasally during the experiments on a model of influenza pneumonia in mice. The degree of this activity was in inverse proportion to the time window between the application of the extract and the infection of the animals. The virus, pre-incubated with C.salviifolius extract, did not cause death in the animals. The data obtained indicate that C.salviifolius extract serves as an effective and broad-range means of preventing respiratory viral infections in humans.

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