• Korean Journal of Clinical Pharmacy
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• v.21 no.4
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• pp.353-363
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• 2011

The World Health Organization (WHO) declared the outbreak of H1N1 pandemic in 2009. South Korea also had outbreaks of H1N1 virus and used oseltamivir in large volume with increased reports of adverse drug reaction(ADR). The present study was aimed to investigate the ADR frequency, the factors related to ADR, and characteristics of oseltamivir's ADR. Participants for the study were patients randomly drawn from those who were prescribed oseltamivir for treatment from CHA Bundang Medical Center during October 1 and October 30. The information examined as factors related to ADR were collected by a subsequent cross-sectional telephone survey. The factors are the following; a) age; b) gender; c) patient medical history; d) diagnosis of H1N1 virus; e) adherence; f) whether taking other medication with oseltamivir or not; and g) the number of combined medications. We also asked ADR after taking oseltamivir. Total subjects were 86 patients. The average age is $22.6{\pm}18.48$ years old. The gender was 45.3% women and 54.7% men. Half (50%) of all respondents showed one or more ADR, 67.4% were positively diagnosed for H1N1 virus, and 54.7% were completed the full course of oseltamivir (i.e. twice daily x 5days). The most frequently reported ADR symptoms were: dizziness (15.1%), nausea (11.6%), lethargy (10.4%), diarrhea (10.4%), abdominal pain (8.1%), headache and vomiting (6.9%). ADR classifications by categories are gastro intestinal (44.2%), neuropsychiatric events (22.1%), systemic symptom (20.9%), skin events (5.8%), eye events (4.7%), and other cases (2.3%). The onset of ADR 'after taking 1~3 doses' was 69.7%. No increase in neuropsychiatric events was detected in children and adolescents. No factors examined for the study do have significant influence on the presence of ADR. This study showed that ADR of oseltamivir have occurred in half of the patients. The use of oseltamivir is essential for treatment and prophylaxis of influenza A(H1N1). But mass treatment should be properly monitored for ADR.

• IMMUNE NETWORK
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• v.9 no.5
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• pp.169-178
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• 2009

DNA immunization induces B and T cell responses to various pathogens and tumors. However, these responses are known to be relatively weak and often transient. Thus, novel strategies are necessary for enhancing immune responses induced by DNA immunization. Here, we demonstrated that co-immunization of influenza virus nucleoprotein (NP) gene significantly enhances humoral and cell-mediated responses to codelivered antigens in mice. We also found that NP DNA coimmunization augments in vivo proliferation of adoptively transferred antigen-specific CD4 and CD8 T cells, which enhanced protective immunity against tumor challenge. Our results suggest that NP DNA can serve as a novel genetic adjuvant in cocktail DNA vaccination.

• YAKHAK HOEJI
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• v.43 no.4
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• pp.469-473
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• 1999

EA, the water soluble substance, was prepared from the carpophores of Elfvingia applanata (Pers). Karst. Anti-influenza A virus (anti-Flu A) activity of EA was examined of Vero cells by plaque reduction assay in vitro. And the combined antiviral effects fo EA with interferon (IFN) alpha and gamma were examined on the multiplication of Flu A with 50% effective concentration ($EC_50$) of 1.50 mg/ml. The results of combination assay were evaluated by the combination index (CI) that was analysed by the multiple drug effect analysis. The combination of EA with IFN alpha on Flu A showed more potent synergism with CI values of 0.50~0.52 of 50%, 70%, 90% effective levels than that with IFN gamma with CI values of 0.82~0.99.

• Clinical and Experimental Pediatrics
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• v.54 no.10
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• pp.422-424
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• 2011

Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the central nervous system that typically follows an infection or vaccination and has a favorable long-term prognosis. We describe the first reported case of ADEM after vaccination against novel influenza A (H1N1). A previously healthy 34-month-old boy who developed ADEM presented with a seizure and left-sided weakness 5 days after vaccination against novel influenza A (H1N1). Cerebrospinal fluid examination revealed elevated cell counts. T2-weighted images and fluid-attenuated inversion recovery images revealed multiple patchy hyperintense lesions in the frontal and parietal subcortical white matter and the left thalamus. After the administration of intravenous corticosteroid, the patient's clinical symptoms improved and he recovered completely without neurologic sequelae.

• Journal of Microbiology and Biotechnology
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• v.26 no.11
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• pp.1972-1982
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• 2016

Influenza A virus is a single-stranded RNA virus with a genome of negative polarity. Owing to the antigenic diversity and cross concrete shift, an immense number of novel strains have developed astronomically over the years. The present work deals with the codon utilization partialness among five different influenza A viruses isolated from human hosts. All the subtypes showed the homogeneous pattern of nucleotide utilization with a little variation in their utilization frequencies. A lower bias in codon utilization was observed in all the subtypes as reflected by higher magnitudes of an efficacious number of codons. Dinucleotide analysis showed very low CpG utilization and a high predilection of A/T-ending codons. The H5N1 subtype showed noticeable deviation from the rest. Codon pair context analysis showed remarkable depletion of NNC-GNN and NNT-ANN contexts. The findings alluded towards GC-compositional partialness playing a vital role, which is reflected in the consequential positive correlation between the GC contents at different codon positions. Untangling the codon utilization profile would significantly contribute to identifying novel drug targets that will pacify the search for antivirals against this virus.

• Biomedical Science Letters
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• v.17 no.4
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• pp.297-304
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• 2011

Influenza A virus of the Orthomyxoviridae family is a contagious respiratory pathogen that continues to evolve and burden in the human public health. It is able to spread efficiently from human to human and have the potential to cause pandemics with significant morbidity and mortality. It has been estimated that every year about 500 million people are infected with this virus, causing about approximately 0.25 to 0.5 million people deaths worldwide. Influenza A viruses are classified into different subtypes by antigenicity based on their hemagglutinin (HA) and neuraminidase (NA) proteins. The sudden emergence of influenza A virus subtypes and access for epidemiological analysis of this subtypes demanded a rapid development of specific diagnostic tools. Also, rapid identification of the subtypes can help to determine the antiviral treatment, because the different subtypes have a different antiviral drug resistance patterns. In this study, our aim is to detect influenza A virus subtypes by using real-time nucleic acid sequence based amplification (NASBA) which has high sensitivity and specificity through molecular beacon. Real-time NASBA is a method that able to shorten the time compare to other molecular diagnostic tools and is performed by isothermal condition. We selected major pandemic influenza A virus subtypes, H3N2 and H5N1. Three influenza A virus gene fragments such as HA, NA and matrix protein (M) gene were targeted. M gene is distinguished influenza A virus from other influenza virus. We designed specific primers and molecular beacons for HA, NA and M gene, respectively. In brief, the results showed that the specificity of the real-time NASBA was higher than reverse transcription polymerase chain reaction (RT-PCR). In addition, time to positivity (TTP) of this method was shorter than real-time PCR. This study suggests that the rapid detection of neo-appearance pandemic influenza A virus using real-time NASBA has the potential to determine the subtypes.

• Journal of Life Science
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• v.32 no.5
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• pp.375-390
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• 2022

Influenza viruses are zoonotic respiratory pathogens, and influenza infections have caused a substantial burden on public health systems and the livestock industry. Although currently approved seasonal influenza vaccines have shown potent protection efficacy against antigenically well-matched strains, there are considerable unmet needs for the efficient control of viral infections. Enormous efforts have been made to develop broadly protective universal influenza vaccines to tackle the huge levels of genetic diversity and variability of influenza viruses. In addition, antiviral drugs have been considered important interventions for the treatment of viral infections. The viral neuraminidase inhibitor oseltamivir is the most widely used antiviral medication to treat influenza A and influenza B viruses. However, unsatisfactory clinical outcomes resulting from side effects and the emergence of resistant variants have led to greater attention being paid to plants as a natural resource for anti-influenza drugs. In particular, the recent COVID-19 pandemic has underpinned the need for safe and effective antiviral drugs with a broad spectrum of antiviral activity to prevent the rapid spread of viruses among humans. This review outlines the results of the antiviral activities of various natural products isolated from plants against influenza viruses. Special focus is paid to the virucidal effects and the immune-enhancing effects of antiviral natural products, since the products have broad applications as inactivating agents for the preparation of inactivated vaccines and vaccine adjuvants.

• IMMUNE NETWORK
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• v.20 no.4
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• pp.32.1-32.15
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• 2020

Influenza virus is the major cause of seasonal and pandemic flu. Currently, oseltamivir, a potent and selective inhibitor of neuraminidase of influenza A and B viruses, is the drug of choice for treating patients with influenza virus infection. However, recent emergence of oseltamivir-resistant influenza viruses has limited its efficacy. Morin hydrate (3,5,7,2',4'-pentahydroxyflavone) is a flavonoid isolated from Morus alba L. It has antioxidant, anti-inflammatory, neuroprotective, and anticancer effects partly by the inhibition of the NF-κB signaling pathway. However, its effects on influenza virus have not been studied. We evaluated the antiviral activity of morin hydrate against influenza A/Puerto Rico/8/1934 (A/PR/8; H1N1) and oseltamivir-resistant A/PR/8 influenza viruses in vitro. To determine its mode of action, we carried out time course experiments, and time of addition, hemolysis inhibition, and hemagglutination assays. The effects of the co-administration of morin hydrate and oseltamivir were assessed using the murine model of A/PR/8 infection. We found that morin hydrate reduced hemagglutination by A/PR/8 in vitro. It alleviated the symptoms of A/PR/8-infection, and reduced the levels of pro-inflammatory cytokines and chemokines, such as TNF-α and CCL2, in infected mice. Co-administration of morin hydrate and oseltamivir phosphate reduced the virus titers and attenuated pulmonary inflammation. Our results suggest that morin hydrate exhibits antiviral activity by inhibiting the entry of the virus.

• Journal of Preventive Medicine and Public Health
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• v.43 no.2
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• pp.109-116
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• 2010

Objectives: The pandemic of novel influenza A (H1N1) virus has required decision-makers to act in the face of the substantial uncertainties. In this study, we evaluated the potential impact of the pandemic response strategies in the Republic of Korea using a mathematical model. Methods: We developed a deterministic model of a pandemic (H1N1) 2009 in a structured population using the demographic data from the Korean population and the epidemiological feature of the pandemic (H1N1) 2009. To estimate the parameter values for the deterministic model, we used the available data from the previous studies on pandemic influenza. The pandemic response strategies of the Republic of Korea for novel influenza A (H1N1) virus such as school closure, mass vaccination (70% of population in 30 days), and a policy for anti-viral drug (treatment or prophylaxis) were applied to the deterministic model. Results: The effect of two-week school closure on the attack rate was low regardless of the timing of the intervention. The earlier vaccination showed the effect of greater delays in reaching the peak of outbreaks. When it was no vaccination, vaccination at initiation of outbreak, vaccination 90 days after the initiation of outbreak and vaccination at the epidemic peak point, the total number of clinical cases for 400 days were 20.8 million, 4.4 million, 4.7 million and 12.6 million, respectively. The pandemic response strategies of the Republic of Korea delayed the peak of outbreaks (about 40 days) and decreased the number of cumulative clinical cases (8 million). Conclusions: Rapid vaccination was the most important factor to control the spread of pandemic influenza, and the response strategies of the Republic of Korea were shown to delay the spread of pandemic influenza in this deterministic model.

• Journal of Integrative Natural Science
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• v.8 no.3
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• pp.209-213
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• 2015

Influenza A virus (H1N1) causes and spreads infectious diseases and becomes a major health threat in humans. Among the subtypes of influenza virus, neuraminidase (NA) plays an important role in viral life cycle and becomes an attractive therapeutic target. Currently two NA inhibitors namely Zanamivir and Oseltamivir are available for treating infectious diseases. Recently five naturally derived polyphenols extracted from Phellinus baumii was reported as inhibitors against NA. Molecular docking is powerful tool in computer aided drug designing which aids in exploring and elucidating the properties of the molecules from their 3D structure. Hence, in the present study, molecular docking was carried out on reported polyphenols isolated from ethanolic extract of fruiting bodies of Phellinus baumii. The objective of this work was to study the interaction and to propose the binding mode of these compounds within the binding site of H1N1 neuraminidase. The results showed these compounds had better binding energy and H-bond interactions with the important active site residues of the receptor which authenticate these compounds contributes to inhibitory activity of neuraminidase to treat influenza infection.