• Bulletin of the Korean Chemical Society
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• v.34 no.2
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• pp.545-548
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• 2013

It has been shown that calculating atomic charges using quantum mechanical level theory greatly improves the accuracy of docking. A protocol was developed and shown to be effective. That this protocol works is just a manifestation of the fact that electrostatic interactions are important in protein-ligand binding. In order to investigate how the same protocol helps in prediction of binding affinities, we took a series of known cocrystal structures of influenza neuraminidase inhibitors with the receptor and performed docking with Glide SP, Glide XP, and QPLD, the last being a workflow that incorporates QM/MM calculations to replace the fixed atomic charges of force fields with quantum mechanically recalculated ones at a given docking pose, and predicted the binding affinities of each cocrystal. The correlation with experimental binding affinities considerably improved with QPLD compared to Glide SP/XP yielding $r^2$ = 0.83. The results suggest that for binding sites, such as that of neuraminidase, which are laden with hydrophilic residues, protocols such as QPLD which utilizes QM-based atomic charges can better predict the binding affinities.

• 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.

• Mycobiology
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• v.47 no.2
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• pp.256-260
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• 2019

Neuraminidase (NA) cleaves the glycosidic bond linkages of sialic acids to release the mature virions from infected cells and has been an attractive therapeutic target for anti-influenza agents. In our ongoing investigation of NA inhibitors in mushroom extracts, we found that the extract the fruiting body of Glaziella splendens potently inhibited neuraminidase. The fruiting bodies of G. splendens were extracted and partitioned successively with hexane, ethyl acetate, and butanol. The ethyl acetate soluble-layer was subjected to silica gel and Sephadex LH-20 column chromatographies, and MPLC to obtain five compounds (1-5). Their structures were determined by spectroscopic methods. NA inhibitory activity of these compounds was evaluated using NAs from recombinant rvH1N1, H3N2, and H5N1 influenza A viruses. One compound (1) was elucidated as a new azaphilone derivative, and four compounds (2-5) were identified as entonaemin A, comazaphilone D, rubiginosin A, and entonaemin B, respectively. Compounds 3 and 4 showed considerable inhibitory activity against three types of neuraminidases with the $IC_{50}$ values of 30.9, 41.8, and $35.7{\mu}M$ for 3 and 46.5, 50.4, and $29.9{\mu}M$ for 4, respectively. This study reveals that the fruiting bodies of G. splendens possess azaphilone derivatives with the NA inhibitory activity. This is the first report on the isolation of neuraminidase inhibitors from the fruiting bodies of G. splendens.

• Bulletin of the Korean Chemical Society
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• v.25 no.10
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• pp.1575-1577
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• 2004

• The Korean Journal of Zoology
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• v.29 no.3
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• pp.171-180
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• 1986

The effects of proteases, neuraminidase and EDTA on adhesion of amoebae on the substratum, ultrastructure and biochemical composition of the cell surface were studied by concanavalin A (con A) cytochemistry and SDS PAGE. By con A cytochemistry the glycocalyx of the plasmalemma was easily subdivided into outer filamentous (F) layer and the inner amorphous (A) layer. On treatment with neuraminidase, amoebae attached to the substratum and spreaded better than untreated cells exposing the more con A binding sites in A- and F-layer. When the cells were treated with trypsin or proteinase K, cells stayed unattached for 12 and 48 hr, respectively. Con A binding sites of A layer and all of those glycoproteins were removed by proteinase K. On the other hand, trypsin damaged all of the con A binding sites in both A- and F-layer without significant change in PAS-stained profile of the plasmalemma. Some of the mucopolysaccharides of the cell surface were released by these enzymes and EDTA. When the cells were incubated with monovalent con A they did not attch on the substratum and cytolysed. From these results adhesion of amoebae on the substratum appears to be mediated by the interaction of the glycoproteins and mucopolysaccharides of the A layer.

• Mycobiology
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• v.44 no.2
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• pp.117-120
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• 2016

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 $IC_{50}$ values in the range of $0.7{\sim}8.1{\mu}M$.

• 한국균학회소식:학술대회논문집
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• 2016.05a
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• pp.41-41
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• 2016

Influenza viruses are RNA viruses that belong to the Orthomyxoviridae family, and those can be divided into three types; A, B, and C, which based on the differences of the inner nucleoproteins and genomic structures. All three genera differ in their genomic structure and nucleoprotein content, they are further classified into various serotypes based on the two surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA). These glycoproteins play crucial roles in viral infection and replication. Hemagglutinin mediates binding of virions to sialic acid receptors on the surfaces of target cells at the initial stage of infection. Neuraminidase cleaves the glycosidic bonds of sialic acids from the viral and cell surfaces to release the mature virions from infected cells, after viral replication. Because NA plays an important role in the viral life cycle, it is considered an attractive therapeutic target for the treatment of influenza. The methanolic extracts of Phellinus baumii and Phellinus igniarius exhibited significant activity in the neuraminidase inhibition assay. Polyphenolic compounds were isolated from the methanolic extracts. The structures of these compounds were determined to be hispidin, hypholomine B, inoscavin A, davallialactone, phelligridin D, phelligridin E, and phelligridin G by spectroscopic methods. Compounds inhibited the H1N1 neuraminidase activity in a dose-dependent manner with $IC_{50}$ values of 50.9, 22.9, 20.0, 14.2, 8.8, 8.1 and $8.0{\mu}M$, respectively. Moreover, these compounds showed anti-influenza activity in the viral cytopathic effect (CPE) reduction assay using MDCK cells. These results suggests that the polyphenols from P. baumii and P. igniarius are promising candidates for prevention and therapeutic strategies against viral infection.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.6 no.1
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• pp.32-39
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• 2006

Galactosialidosis is a lysosomal storage disease associated with a combined deficiency of ${\beta}$-galactosidase and ${\alpha}$-neuraminidase, secondary to a defect of another lysosomal protective protein. It is a neurodegenerative disorder clinically characterized by psychomotor deterioration, cerebellar ataxia, coarse facies, generalized bony deformity and organomegaly. Three phenotypic subtype are recognized: early infantile, late infantile and juvenile/adult type. We report a 13 months old boy with a late infantile galactosialidosis. He was presented with progressive mental regression and motor disturbance and observed cherry red spot, hearing loss, moderate dysostosis multiplex and vacuolated lymphocytes in peripheral blood. He showed only ${\beta}$-galactosidase deficiency in the lymphocytes and was initially diagnosed as $GM_1$-gangliosidosis type 1. However, further studies revealed the possible defect of ${\alpha}$-neuraminidase suggesting that he was a case of galactosialidosis which was mimicking $GM_1$-gangliosidosis type 1.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.1-6
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• 2023

Dendranthema zawadskii is a one of the popular plants as native in South Korea. In this study, linarin was isolated and purified using silica-gel, Diaion, and Sephadex LH-20 from the aerial parts of D. zawadskii. The chemical structure was completely identified through spectroscopic data including 1D, 2D nucleic magnetic resonance, and HRFABMS. Furthermore, linarin inhibited the bacterial neuraminidase (BNA) activity with 13.5 μM of IC₅₀ dose-dependently. Through the enzyme kinetic experiments, linarin as BNA inhibitor exhibited a typical noncompetitive inhibition mode which K_m was contestant and V_max decreased as the concentration of the inhibitor increased. It was further identified that the inhibition constant was 16.0 μM. Linarin was the most abundance metabolite in the aerial part of D. zawadskii extract by UHPLC-TOF/MS analysis. Therefore, D. zawadskii and its main component are expected that it can be effectively used for the infection and inflammation caused by bacteria.

• Microbiology and Biotechnology Letters
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• v.48 no.3
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• pp.303-309
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• 2020

The purpose of this study was to identify the changes in the components of unfermented Gongjin-dan (GD) and fermented Gongjin-dan (FGD) and to confirm whether GD or FGD has an inhibitory effect on viral neuraminidase (NA) activity. A major component of FGD was isolated and identified as nodakenetin, which is the aglycone of nodakenin. After fermentation, the nodakenetin content in FGD was approximately 10-fold higher than that in GD. Then, we examined the viral NA-inhibitory activity of GD, FGD, nodakenin, and nodakenetin. At a concentration of 500 ㎍/ml, FGD inhibited viral NA activity by 92% compared to the DMSO-treated control, while GD barely inhibited viral NA activity. In addition, 250 ㎍/ml of nodakenetin inhibited viral NA activity by 68% compared to the control, while nodakenin inhibited viral NA activity by only 4% at the same concentration as nodakenetin. Collectively, these results suggest that FGD has a more remarkable viral NA-inhibitory activity than GD because the content of the anti-viral component nodakenetin was higher in FGD due to the hydrolysis of nodakenin by Lactobacillus plantarum KCTC 3104.