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Bacteroides fragilis* ; Bacteroides* ; Genetic Structures* ; Neuraminidase*

In annual epidemics and occasional pandemics, influenza viruses cause acute respiratory illnesses in infected humans. Vaccines and antiviral drugs are two main arsenals available for a fight against influenza viruses. However, vaccines often exhibit a limited efficacy in high risk populations, and antiviral drugs are always concerned for mutations, which confer viral resistance. Here we review current advances and knowledge in relation to the usage of antiviral drugs as a prophylactic or therapeutic and the mechanism of resistant variants mainly against the neuraminidase inhibitors. Comprehensive understanding of the resistant mechanism will pave a road for developing new antivirals and/or finding medical or natural alternatives inducing less frequent resistance, and application of combination therapy using two or three different kinds of antivirals can suggest a useful medical intervention against both of seasonal and highly pathogenic influenza viruses including resistant variants. In this review, we provide insights of antiviral drugs for the control and prevention of influenza viruses.
Antiviral Agents ; Humans ; Influenza, Human ; Neuraminidase ; Orthomyxoviridae ; Pandemics ; Seasons ; Vaccines

During our ongoing investigation of neuraminidase inhibitors from medicinal fungi, we found that the fruiting bodies of Phellinus igniarius exhibited significant inhibitory activity against neuraminidase from recombinant H3N2 influenza viruses. Two active compounds were isolated from the methanolic extract of P. igniarius through solvent partitioning and Sephadex LH-20 column chromatography. The active compounds were identified as phelligridins E and G on proton nuclear magnetic resonance (¹H NMR) and electrospray ionization mass measurements. These compounds inhibited neuraminidases from recombinant rvH1N1, H3N2, and H5N1 influenza viruses, with IC₅₀ values in the range of 0.7~8.1 µM.
Chromatography ; Fruit* ; Fungi ; Magnetic Resonance Spectroscopy ; Methanol ; Neuraminidase* ; Orthomyxoviridae ; Protons

Oseltamivir is a potent selective neuraminidase enzyme inhibitor and effective against nearly all strains of influenza A and B. The importance of treating influenza has been recognized, and oseltamivir has been prescribed frequently at the onset of the H1N1 influenza A pandemic this year. However, oseltamivir can cause hemorrhagic colitis as a rare adverse effect. Until now, only two cases of hemorrhagic colitis following the use of oseltamivir have been reported in Japan, and none have been reported in Korea. We report a case of acute hemorrhagic colitis in a 15-year-old boy after the oral administration of oseltamivir for swine originating influenza A.
Administration, Oral ; Adolescent ; Colitis ; Humans ; Influenza, Human ; Japan ; Korea ; Neuraminidase ; Oseltamivir ; Pandemics ; Swine

Twelve nucleotides located at the 3′ end of viral genomic RNA (vRNA) are conserved among influenza A viruses (IAV) and have a promoter function. Hoffmann's 8-plasmid reverse genetics vector system introduced mutations at position 4, C nucleotide (C4) to U nucleotide (U4), of the 3′ ends of neuraminidase (NA) and matrix (M) vRNAs of wild-type A/PR/8/34 (PR8). This resulted in a constellation of C4 and U4 vRNAs coding for low (polymerases) and relatively high (all others) copy number proteins, respectively. U4 has been reported to increase promoter activity in comparison to C4, but the constellation effect on the replication efficiency and pathogenicity of reverse genetics PR8 (rgPR8) has not been fully elucidated. In the present study, we generated 3 recombinant viruses with C4 in the NA and/or M vRNAs and rgPR8 by using reverse genetics and compared their pathobiological traits. The mutant viruses showed lower replication efficiency than rgPR8 due to the low transcription levels of NA and/or M genes. Furthermore, C4 in the NA and/or M vRNAs induced lower PR8 virus pathogenicity in BALB/c mice. The results suggest that the constellation of C4 and U4 among vRNAs may be one of the multigenic determinants of IAV pathogenicity.
Animals ; Clinical Coding ; Influenza A virus ; Influenza, Human* ; Mice ; Neuraminidase* ; Nucleotides ; Orthomyxoviridae* ; Reverse Genetics ; RNA* ; Virulence*

PURPOSE: Nitrocellulose membrane–based filtration system (NCFS) is widely used for protein concentration. In this study, we applied NCFS for production of virus-like particle (VLP) as a vaccine candidate and evaluated yield property and immunogenicity. MATERIALS AND METHODS: Influenza VLPs were generated by baculovirus-insect cell protein expression system. NCFS and sucrose gradient ultracentrifugation were used for purification of VLP. Immunogenicity of VLP was evaluated by animal experiment. RESULTS: Influenza VLPs expressing hemagglutinin (HA) and neuraminidase proteins derived from highly pathogenic influenza virus (H5N8) were effectively produced and purified by NCFS. HA activity of VLP which correlated with antigenicity was well conserved during multiple purification steps. This NCFS based purified VLPs induced influenza virus–specific antibody responses. CONCLUSION: Our results indicate that the influenza VLP vaccine could be prepared by NCFS without loss of immunogenicity and elicit antigen-specific immune responses.
Animal Experimentation ; Antibody Formation ; Baculoviridae ; Collodion* ; Filtration* ; Hemagglutinins ; Influenza, Human* ; Membranes* ; Neuraminidase ; Orthomyxoviridae ; Sucrose ; Ultracentrifugation ; Vaccines

Influenza viruses cause annual epidemics and occasional pandemics that have claimed the millions of lives. On December 4th 2009, more than 207 countries and overseas territories have reported laboratory confirmed cases of pandemic influenza H1N1 2009, which has claimed at least 8768 lives. Up to this date, the pandemic influenza H1N1 2009 has spread throughout the world with unprecedented speed. Accurate and rapid diagnosis of this influenza virus is critical for minimizing further spread, combined with timely implementation of antiviral treatment and public health based measures. Recently, the percentage of oseltamivir-resistant human seasonal H1N1 has increased to 98.5% in USA, and 99.8% in Korea. Fortunately, the pandemic influenza H1N1 2009 is sensitive to neuraminidase inhibitors, including oseltamivir. However, the percentage oseltamivir-resistant pandemic influenza H1N1 2009 is expected to increase with time. In this review, the various diagnostic method and the antiviral agents that have been reported in the literature will be discussed.
Antiviral Agents ; Humans ; Influenza, Human ; Korea ; Neuraminidase ; Orthomyxoviridae ; Oseltamivir ; Pandemics ; Public Health ; Seasons

OBJECTIVE: To perform a systematic review to assess the effectiveness and safety of Reduning Injection versus neuraminidase inhibitors in treatment of influenza. METHODS: The MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), Chinese Bio-medical Literature and Retrieval System (Sinomed), China National Knowledge Infrastructure Database (CNKI), China Science and Technology Journal Database (VIP), Wanfang Data Knowledge Service Platform and ClinicalTrails.gov were systematically searched from inception dates to May 2021 for randomized controlled trials (RCTs) exploring Reduning Injection alone or in combination with neuraminidase inhibitors in patients with influenza. Statistical analysis was performed using RevMan 5.4 and Stata 15.1. The qualities of the involved studies were assessed by the risk of bias according to the Cochrane handbook. The evidence quality of each outcome was evaluated by GRADEpro GDT. RESULTS: Twelve trials with 1,460 patients were included. The included studies had a certain unclear or high risk of bias. Reduning Injection appeared to be more effective in shortening the fever clearance time (MD: -16.20 h, 95% CI: -19.40 to -12.99, 7 trials, 814 patients, I²=94%, very low certainty), fever alleviation time (MD: -4.09 h, 95% CI: -4.22 to -3.96, 3 trials, 366 patients, I²=0%, low certainty), cough alleviation time (MD: -21.34 h, 95% CI: -41.56 to -1.11, 2 trials, 228 patients, I²=89%, very low certainty), fatigue alleviation time (MD: -31.83 h, 95% CI: -36.88 to -26.77, 2 trials, 270 patients, I²=0%, low certainty), sore throat alleviation time (MD: -28.66 h, 95% CI: -32.23 to -25.10, 1 trial, 150 patients, low certainty), and improving the total effective rate (RR: 1.15, 95% CI: 1.06 to 1.25, 10 trials, 1,074 patients, I²=76%, very low certainty). Besides, Reduning Injection seemed generally safe. CONCLUSIONS This study provided low or very low evidence indicating Reduning Injection may be effective in the treatment of influenza and might be safe. Further rigorously designed studies are needed to confirm the effectiveness and safety of Reduning Injection and support it as a recommendation for influenza.
Humans ; Neuraminidase ; Influenza, Human/drug therapy* ; Drugs, Chinese Herbal ; Antiviral Agents

LG1 strain of avian influenza virus H9N2 was passaged continuously for 40 generations in chicken embryos with anti-LG1 maternal antibodies in 4 parallel experiments, of which 3 experiments had a stable mutation of "G" to "A" at #99 of the neuraminidase gene(NA)from the 20th passage resulting in a change of Met to Ile and 2 had a stable mutation of "A" to "G" at #473 of the NA gene from the 30th passage resulting in a change of Asn to Ser which occurred in the 50th passage of another experiment. Eighty continuous passages in chicken embryos without antibody did not have the same mutation, indicating that the mutations of the 2 positions were associated with selective pressure of antibodies. Analysis of the ratios of nonsynonium (NS) vs synonium (S) mutations of nucleic acids demonstrated that NS/S of 4 parallel experiments with antibodies was 4.6 (32/7) compared with 2.0 (16/8) of the 2 experiments without antibodies and this significant difference implied the selective pressure of antibodies.
Animals ; Antibodies, Viral ; immunology ; Chick Embryo ; Influenza A Virus, H9N2 Subtype ; genetics ; immunology ; Mutation ; Neuraminidase ; genetics

Cell Line, Tumor ; Genetic Vectors ; Humans ; Male ; Neuraminidase ; genetics ; metabolism ; Prostate ; metabolism ; Prostatic Neoplasms ; metabolism ; pathology