• Bulletin of the Korean Chemical Society
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• v.29 no.11
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• pp.2221-2226
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• 2008

• Biomolecules & Therapeutics
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• v.21 no.2
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• pp.161-169
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• 2013

The objective of this study was to enhance the oral bioavailability (BA) of zanamivir (ZMR) by increasing its intestinal permeability using permeation enhancers (PE). Four different classes of PEs (Labrasol$^{(R)}$, sodium cholate, sodium caprate, hydroxypropyl ${\beta}$-cyclodextrin) were investigated for their ability to enhance the permeation of ZMR across Caco-2 cell monolayers. The flux and $P_{app}$ of ZMR in the presence of sodium caprate (SC) was significantly higher than other PEs in comparison to control, and was selected for further investigation. All concentrations of SC (10-200 mM) demonstrated enhanced flux of ZMR in comparison to control. The highest flux (13 folds higher than control) was achieved for the formulation with highest SC concentration (200 mM). The relative BA of ZMR formulation containing SC (PO-SC) in plasma at a dose of 10 mg/kg following oral administration in rats was 317.65% in comparison to control formulation (PO-C). Besides, the $AUC_{0-24\;h}$ of ZMR in the lungs following oral administration of PO-SC was $125.22{\pm}27.25$ ng hr $ml^{-1}$ with a $C_{max}$ of $156.00{\pm}24.00$ ng/ml reached at $0.50{\pm}0.00$ h. But, there was no ZMR detected in the lungs following administration of control formulation (PO-C). The findings of this study indicated that the oral formulation PO-SC containing ZMR and SC was able to enhance the BA of ZMR in plasma to an appropriate amount that would make ZMR available in lungs at a concentration higher (>10 ng/ml) than the $IC_{50}$ concentration of influenza virus (0.64-7.9 ng/ml) to exert its therapeutic effect.

• 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 Integrative Natural Science
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• v.4 no.4
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• pp.273-277
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• 2011

It's a threat for the public health that H1N1 (Influenza virus A) causes disease and transmits among humans. WHO (world health organization) declared that the infections caused by the new strain had reached pandemic proportions. The approved neuraminidase inhibitors (Zanamivir and Oseltamivir) and related investigative drug (BCX-1812) are potent, specific inhibitors of influenza A and B viruses. These drugs are highly effective to prevent influenza A and B infections. Early therapeutic use reduces illness duration and respiratory complications. Recently, we found one of the potent inhibitor of erystagallin A ($IC_{50}$ of 2.04 ${\mu}M$) for neuraminidase target, this inhibitor shows most similar structure to its natural substrate, sialic acid. Therefore, we chose 1l7f to get the receptor structure for docking study among many crystal structures. A docking study has been performed in Surflex-Dock module in SYBYL 8.1. In the present study, we attempt to compare the docking studies of pterocarpin and erystagallin A with neuraminidase receptor structure. In the previous report, the methoxy group of pterocarpin had H-bonding with Arg residues. The present docking results for erystagallin A showed the backbone of hydroxyl group shows significant H-bonding interactions with Arg152 and Arg292. The results showed that erystagallin A interacts more favorably with distinctive binding site rather than original active site. Therefore, we tried to reveal plausible binding mode and important amino acid for this inhibitor using docking and site id search calculations of Sybyl. The results obtained from this work may be utilized to design novel inhibitors for neuraminidase.

• Korean Journal of Clinical Laboratory Science
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• v.42 no.1
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• pp.1-15
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• 2010

Swine influenza virus (SIV) or swine-origin influenza virus (S-OIV) is endemic in swine, and classified into influenza A and influenza C but not influenza B. Swine influenza A includes H1N1, H1N2, H3N1, H3N2 and H2N3 subtypes. Infection of SIV occurs in only swine and that of S-OIV is rare in human. What human can be infected with S-OIV is called as zoonotic swine flu. Pandemic 2009 swine influenza H1N1 virus (2009 H1N1) was emerged in Mexico, America and Canada and spread worldwide. The triple-reassortant H1N1 resulting from antigenic drift was contained with HA, NA and PB1 of human or swine influenza virus, PB2 and PA polymerase of avian influenza virus, and M, NP and NS of swine influenza virus, The 2009 H1N1 enables to transmit to human and swine. The symptoms and signs in human infected with 2009 H1N1 virus are fever, cough and sore throat, pneumonia as well as diarrhea and vomiting. Co-infection with other viruses and bacteria such as Streptococcus pneumoniae can occur high mortality in high-risk population. 2009 H1N1 virus was easily differentiated from seasonal flu by real time RT-PCR which contributed rapid and confirmed diagnosis. The 2009 H1N1 virus was treated with NA inhibitors such as oseltamivir (Tamiflu) and zanamivir (Relenza) but not with adamantanes such as amantadine and rimantadine. Evolution of influenza virus has continued in various hosts. Development of a more effective vaccine against influenza prototypes is needed to protect new influenza infection such as H5 and H7 subtypes to infect to multi-organ and cause high pathogenicity.

• Journal of Microbiology and Biotechnology
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• v.23 no.1
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• pp.125-130
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• 2013

Influenza viruses cause significant morbidity and mortality in humans through epidemics or pandemics. Currently, two classes of anti-influenza virus drugs, M2 ion-channel inhibitors (amantadin and rimantadine) and neuraminidase inhibitors (oseltamivir and zanamivir), have been used for the treatment of the influenza virus infection. Since the resistance to these drugs has been reported, the development of a new antiviral agent is necessary. In this study, we examined the antiviral efficacy of the plant extracts against the influenza A/PR/8/34 infection. In vitro, the antiviral activities of the plant extracts were investigated using the cell-based screening. Three plant extracts, Thuja orientalis, Aster spathulifolius, and Pinus thunbergii, were shown to induce a high cell viability rate after the infection with the influenza A/PR/8/34 virus. The antiviral activity of the plant extracts also increased as a function of the concentration of the extracts and these extracts significantly reduced the visible cytopathic effect caused by virus infections. Furthermore, the treatment with T. orientalis was shown to have a stronger inhibitory effect than that with A. spathulifolius or P. thunbergii. These results may suggest that T. orientalis has anti-influenza A/PR/8/34 activity.

• Clinical and Experimental Pediatrics
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• v.56 no.4
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• pp.165-175
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• 2013

Purpose: There was a global increase in the prevalence of oseltamivir-resistant influenza viruses during the 2007-2008 influenza season. This study was conducted to investigate the occurrence and characteristics of oseltamivir-resistant influenza viruses during the 2007-2008 and 2008-2009 influenza seasons among patients who were treated with oseltamivir (group A) and those that did not receive oseltamivir (group B). Methods: A prospective study was conducted on 321 pediatric patients who were hospitalized because of influenza during the 2007-2008 and 2008-2009 influenza seasons. Drug resistance tests were conducted on influenza viruses isolated from 91 patients. Results: There was no significant difference between the clinical characteristics of groups A and B during both seasons. Influenza A/H1N1, isolated from both groups A and B during the 2007-2008 and 2008-2009 periods, was not resistant to zanamivir. However, phenotypic analysis of the virus revealed a high oseltamivir $IC_{50}$ range and that H275Y substitution of the neuraminidase (NA) gene and partial variation of the hemagglutinin (HA) gene did not affect its antigenicity to the HA vaccine even though group A had a shorter hospitalization duration and fewer lower respiratory tract complications than group B. In addition, there was no significant difference in the clinical manifestations between oseltamivir-susceptible and oseltamivir-resistant strains of influenza A/H1N1. Conclusion: Establishment of guidelines to efficiently treat influenza with oseltamivir, a commonly used drug for treating influenza in Korean pediatric patients, and a treatment strategy with a new therapeutic agent is required.