• Bulletin of the Korean Chemical Society
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• v.31 no.3
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• pp.588-594
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• 2010

Two types of resin-conjugated Tamiflu analogs were synthesized by modifying our original synthetic route of oseltamivir phosphate (Tamiflu). The prepared resins bound to influenza virus neuraminidase, the main target of Tamiflu. The resins will be useful for isolating and identifying presumed endogenous vertebrate proteins that interact with Tamiflu, which might relate to the rarely observed abnormal behavior exhibited by some influenza patients treated with Tamiflu.

• Pediatric Infection and Vaccine
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• v.23 no.2
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• pp.149-154
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• 2016

Although an association of Kawasaki disease (KD) with infectious agents has been suggested, none have been proven to cause KD. In this case study, we present a case of KD with concurrent onset of influenza and Mycoplasma pneumoniae (MP) infections. A 27-month-old boy presented with prolonged fever, cough, and rhinorrhea. During the initial testing, influenza A infection was identified, and he was treated with oseltamivir. Despite the antiviral therapy, the fever persisted, and he had cervical lymph node enlargement, bilateral conjunctival injection, fissured red lips, strawberry tongue, and erythematous skin lesions on the Bacillus Calmette-$Gu{\acute{e}}rin$ vaccination site. Thus, the patient was diagnosed with KD and was treated with intravenous immunoglobulin (IVIG). The result of the initial antimycoplasma immunoglobulin M (IgM) antibody testing and was positive, and an increased IgM titer from baseline was found in a repeat test. We reviewed the hypotheses on pathogens known to be associated with KD and the etiology of KD. Based on our findings, we suspect that symptoms of KD and coronary artery lesions can occur from various infections besides those caused by Mycoplasma species and influenza viruses.

• Clinical and Experimental Pediatrics
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• v.54 no.3
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• pp.117-122
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• 2011

Purpose: Natural history and consequences of the novel 2009 influenza A H1N1(2009 H1N1) infection in immunocompromised pediatric patients are not yet fully understood. In this study, we investigated the clinical features and outcomes of the 2009 H1N1 infection in pediatric patients with hematological and oncological diseases. Methods: We retrospectively reviewed the medical records of 528 patients who had hematological and oncological diseases and who were treated at 7 referral centers located in the Yeungnam region. Among the 528 patients, 27 with definite diagnosis of 2009 H1N1 infection were the subjects of this study. All patients were divided into the following 3 groups: patients who were receiving chemotherapy (group 1), patients who were immunosuppressed due to a nonmalignant hematological disease (group 2), and patients who were off chemotherapy and had undergone their last chemotherapy course within 2 years from the influenza A pandemic (group 3). Results: All 28 episodes of 2009 H1N1 infection were treated with the antiviral agent oseltamivir ($Tamiflu^{(R)}$), and 20 episodes were treated after hospitalization. Group 1 patients had higher frequencies of lower respiratory tract infection and longer durations of fever and hospitalization as compared to those in group 2. Ultimately, all episodes resolved completely with no complications. Conclusion: These results suggest that early antiviral therapy did not influence the morbidity or mortality of pediatric patients with hematological and oncological diseases in the Yeungnam region of Korea after the 2009 H1N1 infection. However, no definite conclusions can be drawn because of the small sample size.

• Clinical and Experimental Pediatrics
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• v.52 no.8
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• pp.862-868
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• 2009

Since its identification in April 2009, a swine-origin H1N1 influenza A virus (S-OIV) which is a reassortment of gene segments from both North American triple-reassortant and Eurasian swine influenza has been widely spread among humans in unexpected rapidity. To date, each gene segment of the 2009 influenza A (H1N1) outbreak viruses have shown high (99.9%) neucleotide sequence identity. As of July 6, 94,512 people have been infected in 122 countries, of whom 429 have died with an overall case-fatality rate of <0.5%. Most confirmed cases of S-OIV infection have been characterized by self-limited, uncomplicated febrile respiratory illness and 38% of cases have also included vomiting or diarrhea. Standard plus droplet precautions should be adhered to at all times. Tests on S-OIV have indicated that current new H1N1 viruses are sensitive to neuraminidase inhibitors (oseltamivir). However, current less virulent S-OIV may evolve into a pathogenic strain or acquire antiviral resistance, potentially with more severe clinical consequences. Efforts to control these outbreaks would be based on our understanding of novel S-OIV and previous influenza pandemics.

• Journal of Microbiology and Biotechnology
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• v.21 no.5
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• pp.449-454
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• 2011

The infection of pandemic influenza viruses such as swine flu (H1N1) and avian flu viruses to the host cells is related to the following two factors: First, the surface protein such as HA (hemagglutinin) and NA (neuraminidase) of the influenza virus. Second, the specific structure of the oligosaccharide [sialic acid(${\alpha}2$-6) galactose(${\beta}1$-4)glucose or sialic acid(${\alpha}2$-3)galactose(${\beta}1$-4)glucose] on the host cell. After recognizing the specific structure of the oligosaccharide on the surface of host cells by the surface protein of the influenza virus, the influenza virus can secrete sialidase and cleave the sialic acid attached on the final position of the specific structure of the oligosaccharide on the surface of host cells. Tamiflu (oseltamivir), known as a remedy of swine flu, has a saccharide analog structure, especially the sialic acid analog. Tamiflu can inhibit the invasion of influenza viruses (swine flu and avian flu viruses) into the host cells by competition with sialic acid on the terminal position of the specific oligosaccharide on the surface of the host cell. Because of the emergence of Tamiflu resistance, the development of new potent anti-influenza inhibitors is needed. The inhibitors with positive-charge groups have potential as antiviral therapeutics, and the strain specificity must also be resolved.

• 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.

• Journal of Ginseng Research
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• v.35 no.1
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• pp.104-110
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• 2011

Korean red ginseng (RG), which is a ginseng treated by heating and steaming, has biological activity similar to Panax ginseng. The effect of ginseng on influenza infection has not been studied although it is known to have a broad range of biological activities. The aim of the study is to investigate the effect of RG extract on influenza A (H1N1) virus infection. We investigated the inhibitory effect of RG extract on plaque formation by influenza A virus in a cell-based plaque assay, and the effect of orally administered RG on influenza A virus infection in mice. RG extract, which was applied at a non-cytotoxic concentration, inhibited plaque formation by influenza A virus in the cell-based plaque assay. The orally administered RG extract ameliorated body weight loss and significantly increased survival in mice infected with influenza A virus. Our results suggest that RG extract has components that reduce the severity of infection by influenza A virus and could potentially be used as a complement to treatment of influenza A virus infections.

• Osong Public Health and Research Perspectives
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• v.9 no.6
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• pp.348-353
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• 2018

Objectives: This study was conducted to determine whether essential oils had anti-influenza A/WS/33 virus activity and whether there were specific compounds associated with this activity. Methods: There were 63 essential oils evaluated for anti-influenza (A/WS/33 virus) activity using a cytopathic effect reduction method. The chemical composition of the anti-influenza essential oils was phytochemically analyzed by gas chromatography-mass spectrometry. Results: The antiviral assays demonstrated that 11 of the 62 essential oils ($100{\mu}g/mL$) possessed anti-influenza activity, reducing visible cytopathic effects of influenza A/WS/33 virus activity by > 30%. Furthermore, marjoram, clary sage and anise oils exhibited anti-influenza A/WS/33 virus activity of > 52.8%. However, oseltamivir (the anti-influenza A and B drug), showed cytotoxicity at the same concentration ($100{\mu}g/mL$) as the essential oils. The chemical composition detected by GC-MS analysis, differed amongst the 3 most potent anti-viral essential oils (marjoram, clary sage and anise oils) except for linalool, which was detected in all 3 essential oils. Conclusion: This study demonstrated anti-influenza activity in 11 essential oils tested, with marjoram, clary sage and anise essential oils being the most effective at reducing visible cytopathic effects of the A/WS/33 virus. All 3 oils contained linalool, suggesting that this may have anti-influenza activity. Further investigation is needed to characterize the antiviral activity of linalool against influenza A/WS/33 virus.

• Journal of Microbiology and Biotechnology
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• v.31 no.9
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• pp.1305-1310
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• 2021

Shikimate is a key high-demand metabolite for synthesizing valuable antiviral drugs, such as the anti-influenza drug, oseltamivir (Tamiflu). Microbial-based strategies for shikimate production have been developed to overcome the unstable and expensive supply of shikimate derived from traditional plant extraction processes. In this study, a microbial cell factory using Corynebacterium glutamicum was designed to overproduce shikimate in a fed-batch culture system. First, the shikimate kinase gene (aroK) responsible for converting shikimate to the next step was disrupted to facilitate the accumulation of shikimate. Several genes encoding the shikimate bypass route, such as dehydroshikimate dehydratase (QsuB), pyruvate kinase (Pyk1), and quinate/shikimate dehydrogenase (QsuD), were disrupted sequentially. An artificial operon containing several shikimate pathway genes, including aroE, aroB, aroF, and aroG were overexpressed to maximize the glucose uptake and intermediate flux. The rationally designed shikimate-overproducing C. glutamicum strain grown in an optimized medium produced approximately 37.3 g/l of shikimate in 7-L fed-batch fermentation. Overall, rational cell factory design and culture process optimization for the microbial-based production of shikimate will play a key role in complementing traditional plant-derived shikimate production processes.

• Korean Journal of Clinical Pharmacy
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• v.21 no.2
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• pp.138-144
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• 2011

In order to minimize such adverse drug reactions, governments and international organs have been on the watch for them. Also in South Korea, a system has been established in order that adverse drug reactions may be reported to Korea Food and Drug Administration(KFDA). This study is to analyze drugs to cause adverse reactions, the adverse reactions and patients concerned on the authority of the data of Korea FDA, which is expected to be the preliminary data on preventable adverse reactions. This study was conducted on the 74,037 cases of adverse drug reactions reported to Korea FDA between January 2007 and June 2010. Fentanyl, iopromide and tramadol caused adverse reactions with high frequencies. Oseltamivir showed a high frequency between 2009 and 2010 due to the influence of the new influenza A. Also, OTC drugs accounted for approximately 5% of the adverse reactions. In 2009, adverse drug reactions remarkably increased (2,106 cases; 10.1%) in infants and children due to the new influenza-A(H1N1). The patients aged between 31 and 64 accounted for approximately 55% during the given period. There was no significant intergender difference. In relation to regions, the adverse reactions most frequently occurred in the gastrointestinal system and the integumentary system for three and half years. In addition to anticancer drugs and immunosuppressive drugs that are known to cause adverse reactions frequently, not a few of OTC drugs and external preparations caused such reactions. In particular, the drugs containing specific ingredients caused adverse reactions more frequently than others from 2007 until the first half of 2010. It is advisable for prescribers to acquaint themselves with such adverse reactions and to prescribe drugs other than them. They also have need to sensibly cope with adverse drug reactions just in case they have no substitute drugs. In addition, patients also need to be trained to understand possible adverse reactions in order that they can sensibly accommodate them or choose healthcare services. The results of this study are expected to be helpful to minimize adverse drug reactions.