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Seok-Joon Kwon, Dong Hee Na, Jong Hwan Kwak, Marc Douaisi, Fuming Zhang, Eun Ji Park, Jong-Hwan Park, Hana Youn, Chang-Seon Song, Ravi S Kane, Jonathan S Dordick, Kyung Bok Lee, Robert J Linhardt
Rapid change and zoonotic transmission to humans have enhanced the virulence of the influenza A virus (IAV). Neutralizing antibodies fail to provide lasting protection from seasonal epidemics. Furthermore, the effectiveness of anti-influenza neuraminidase inhibitors has declined because of drug resistance. Drugs that can block viral attachment and cell entry independent of antigenic evolution or drug resistance might address these problems. We show that multivalent 6'-sialyllactose-polyamidoamine (6SL-PAMAM) conjugates, when designed to have well-defined ligand valencies and spacings, can effectively inhibit IAV infection...
October 24, 2016: Nature Nanotechnology
José Peña, Haiyin Chen-Harris, Jonathan E Allen, Mona Hwang, Maher Elsheikh, Shalini Mabery, Helle Bielefeldt-Ohmann, Adam T Zemla, Richard A Bowen, Monica K Borucki
In vivo serial passage of non-pathogenic viruses has been shown to lead to increased viral virulence, and although the precise mechanism(s) are not clear, it is known that both host and viral factors are associated with increased pathogenicity. Under- or overnutrition leads to a decreased or dysregulated immune response and can increase viral mutant spectrum diversity and virulence. The objective of this study was to identify the role of viral mutant spectra dynamics and host immunocompetence in the development of pathogenicity during in vivo passage...
January 2016: Virus Evolution
Wenfei Zhu, Hong Zhang, Xingyu Xiang, Lili Zhong, Lei Yang, Junfeng Guo, Yiran Xie, Fangcai Li, Zhihong Deng, Hong Feng, Yiwei Huang, Shixiong Hu, Xin Xu, Xiaohui Zou, Xiaodan Li, Tian Bai, Yongkun Chen, Zi Li, Junhua Li, Yuelong Shu
In 2015, a novel influenza A(H1N1) virus was isolated from a boy in China who had severe pneumonia. The virus was a genetic reassortant of Eurasian avian-like influenza A(H1N1) (EA-H1N1) virus. The hemagglutinin, neuraminidase, and matrix genes of the reassortant virus were highly similar to genes in EA-H1N1 swine influenza viruses, the polybasic 1 and 2, polymerase acidic, and nucleoprotein genes originated from influenza A(H1N1)pdm09 virus, and the nonstructural protein gene derived from classical swine influenza A(H1N1) (CS H1N1) virus...
November 2016: Emerging Infectious Diseases
Alexandre Guillot, Manuel Dauchez, Nicolas Belloy, Jessica Jonquet, Laurent Duca, Beatrice Romier, Pascal Maurice, Laurent Debelle, Laurent Martiny, Vincent Durlach, Stephanie Baud, Sebastien Blaise
Sialic acids (SA) are monosaccharides that can be located at the terminal position of glycan chains on a wide range of proteins. The post-translational modifications, such as N-glycan chains, are fundamental to protein functions. Indeed, the hydrolysis of SA by specific enzymes such as neuraminidases can lead to drastic modifications of protein behavior. However, the relationship between desialylation of N-glycan chains and possible alterations of receptor function remains unexplored. Thus, the aim of the present study is to establish the impact of SA removal from N-glycan chains on their conformational behavior...
October 19, 2016: Scientific Reports
Hui Zhou, Xin Zhao Deng, Ai Hua Zhang, Ren Xiang Tan
An isocyanide insertion reaction promoted by the combination of an amide and a photoredox is now presented. By using visible light, 6-amidophenanthridine derivatives can be prepared in good chemical yields under mild and eco-friendly reaction conditions. The reaction was shown to proceed through an electron transfer sequence by mechanistic experiments, and thus enabled the efficient production of 24 compounds, each with one new intramolecular aromatic ring obtained. The synthesized compounds were tested to embody good antitumor, antimicrobial and neuraminidase inhibitory activities...
October 18, 2016: Organic & Biomolecular Chemistry
Lei Bao, Lin Ding, Jingjing Hui, Huangxian Ju
A lysosome-accessing nanoprobe is designed for recognition of lysosomal neuraminidases (Lyso-Neus), which can cleave the 4-methylumbelliferone moieties of the substrate from the nanoprobe, and lead to the escape of the moieties from acidic lysosomes into the neutral cytosol assisted by cationic poly(ethyleneimine) to light up the pH-responsive fluorescence for visual detection and dynamic tracking of Lyso-Neu activity in living cells.
October 14, 2016: Chemical Communications: Chem Comm
(no author information available yet)
Avian influenza viruses affect both poultry production and public health. A subtype H5N8 (clade virus, following an outbreak in poultry in South Korea in January 2014, rapidly spread worldwide in 2014-2015. Our analysis of H5N8 viral sequences, epidemiological investigations, waterfowl migration, and poultry trade showed that long-distance migratory birds can play a major role in the global spread of avian influenza viruses. Further, we found that the hemagglutinin of clade virus was remarkably promiscuous, creating reassortants with multiple neuraminidase subtypes...
October 14, 2016: Science
Anna Gillman
Oseltamivir is the best available anti-influenza drug and has therefore been stockpiled worldwide in large quantities as part of influenza pandemic preparedness planning. The active metabolite oseltamivir carboxylate (OC) is stable and is not removed by conventional sewage treatment. Active OC has been detected in river water at concentrations up to 0.86 µg/L. Although the natural reservoir hosts of influenza A virus (IAV) are wild waterfowl that reside in aquatic environments, the ecologic risks associated with environmental OC release and its potential to generate resistant viral variants among wild birds has largely been unknown...
2016: Infection Ecology & Epidemiology
Maheswata Sahoo, Lingaraja Jena, Surya Narayan Rath, Satish Kumar
The influenza A (H1N1) virus, also known as swine flu is a leading cause of morbidity and mortality since 2009. There is a need to explore novel anti-viral drugs for overcoming the epidemics. Traditionally, different plant extracts of garlic, ginger, kalmegh, ajwain, green tea, turmeric, menthe, tulsi, etc. have been used as hopeful source of prevention and treatment of human influenza. The H1N1 virus contains an important glycoprotein, known as neuraminidase (NA) that is mainly responsible for initiation of viral infection and is essential for the life cycle of H1N1...
September 2016: Genomics & Informatics
Robert Moss, James M McCaw, Allen C Cheng, Aeron C Hurt, Jodie McVernon
BACKGROUND: Many nations maintain stockpiles of neuraminidase inhibitor (NAI) antiviral agents for use in influenza pandemics to reduce transmission and mitigate the course of clinical infection. Pandemic preparedness plans include the use of these stockpiles to deliver proportionate responses, informed by emerging evidence of clinical impact. Recent uncertainty about the effectiveness of NAIs has prompted these nations to reconsider the role of NAIs in pandemic response, with implications for pandemic planning and for NAI stockpile size...
October 10, 2016: BMC Infectious Diseases
Vanessa Gonçalves Pereira, Matheus Trovão de Queiroz, Vânia D'Almeida
Mucopolysaccharidosis type I (MPS I) is caused by deficiency of α-l-iduronidase, involved in degradation of glycosaminoglycans. Clinical manifestations are widely variable and patients with severe phenotype present developmental delay and cognitive decline, among other systemic alterations. MPS I patients present secondary accumulation of gangliosides in neuronal cells, besides accumulation of undegraded glycosaminoglycans. Reduction of Neu1 expression has been previously observed in the cerebellum of MPS I mice; to be active, neuraminidase 1 forms the lysosomal multienzyme complex (LMC) with two other proteins, β-galactosidase and protective protein/cathepsin A, involved in stepwise degradation of gangliosides in the lysosomes...
October 6, 2016: Gene
Stephanie C Burke Schinkel, Steven Rubin, Kathryn E Wright
Temperature sensitivity is a phenotype often associated with attenuation of viruses. Previously, we purified several mumps variants from an incompletely attenuated Urabe strain live attenuated vaccine. Here we characterize one isolate that is sensitive to growth at high temperature. This virus was attenuated in a small animal model of mumps virulence, and we identified unique coding substitutions in the hemagglutinin-neuraminidase (HN), the viral polymerase (L) gene, and a non-coding substitution close to the anti-genome promoter sequences...
October 6, 2016: Virus Research
Ismail Hakki Ekin, Kemal Gurturk, Ziya Ilhan, Suat Ekin, Ayse Ebru Borum, Cigdem Arabaci, Abdullah Yesilova
Human and bovine group B streptococcus (GBS) isolates were serotyped and amounts of released N-acetylneuraminic acid from N-acetylneuraminyl-lactose by extracellular neuraminidase were colorimetrically assessed. According to serotyping by co-agglutination method, 30 of bovine GBS and 43 of human GBS could be serotyped (ST) by monospecific antisera coated with protein A. The remaining GBS strains were designated as nontypeable (NT). The released N-acetylneuraminic acid was determined in 90.9% of bovine GBS and 47...
October 6, 2016: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
R Saito, H Akinobu, R A Shaker, I S Akel, A Assaf-Casals, M Lteif, T Odagiri, R Inaba, N Soudani, S Khafaja, S T Ghanem, M Rajab, Y Shobugawa, G S Dbaibo, H Zaraket
Despite the significant burden of influenza outbreaks, active disease monitoring has been largely absent in the Middle East, including Lebanon. In this study we characterized influenza virus in 440 nasopharyngeal swabs collected from patients with acute respiratory infections during two influenza seasons in Lebanon. Influenza A(H3N2) was dominant in the 2013/14 season while the A(H1N1)pdm09 and B/Yamagata strains were most prevalent in the 2014/15 season. All tested isolates were susceptible to 4 neuraminidase inhibitors (oseltamivir, zanamivir, peramivir and laninamivir)...
October 2, 2016: Eastern Mediterranean Health Journal, la Revue de Santé de la Méditerranée Orientale
F Elfalki, H Ihazmad, A Bimouhen, Z Regragui, S Benkaroum, Y Bakri, A Barakat
We monitored phenotypic and genotypic susceptibility of influenza viruses circulating in Morocco during 2014-2015 to oseltamivir and zanamivir. Throat and nasal swab specimens were collected from outpatients (with influenza-like illness) and inpatients (with severe acute respiratory illness) and tested for influenza viruses using real-time reverse transcription polymerase chain reaction. Positive samples were inoculated in MDCK cells and virus phenotypic susceptibility to neuraminidase inhibitors (NAIs) was assessed using fluorescent NA inhibition...
October 2, 2016: Eastern Mediterranean Health Journal, la Revue de Santé de la Méditerranée Orientale
Akinobu Hibino, Hiroki Kondo, Hironori Masaki, Yoshinari Tanabe, Isamu Sato, Nobuhiro Takemae, Takehiko Saito, Hassan Zaraket, Reiko Saito
We report five cases of community- and hospital-acquired infections with oseltamivir- and peramivir-resistant A(H1N1)pdm09 viruses possessing the neuraminidase (NA) H275Y mutation during January-February 2016 in Japan. One case was hospitalized and was receiving oseltamivir for prophylaxis. The remaining four cases were not taking antiviral drugs at the time of sampling. These cases were geographically distant and epidemiologically unrelated. The five viruses showed ~300-fold rise in IC50 values against oseltamivir and peramivir, defined as highly reduced inhibition according to the WHO definition...
October 6, 2016: Virus Genes
Jiraphorn Phanich, Thanyada Rungrotmongkol, Nawee Kungwan, Supot Hannongbua
The H7N9 avian influenza virus is a novel re-assortment from at least four different strains of virus. Neuraminidase, which is a glycoprotein on the surface membrane, has been the target for drug treatment. However, some H7N9 strains that have been isolated from patient after drug treatment have a R292K mutation in neuraminidase. This substitution was found to facilitate drug resistance using protein- and virus- assays, in particular it gave a high resistance to the most commonly used drug, oseltamivir. The aim of this research is to understand the source of oseltamivir resistance using MD simulations and the MM/PB(GB)SA binding free energy approaches...
October 6, 2016: Journal of Computer-aided Molecular Design
Jason R Wilson, Zhu Guo, Adrian Reber, Ram P Kamal, Nedzad Music, Shane Gansebom, Yaohui Bai, Min Levine, Paul Carney, Wen-Pin Tzeng, James Stevens, Ian A York
Zoonotic A(H7N9) avian influenza viruses emerged in China in 2013 and continue to be a threat to human public health, having infected over 800 individuals with a mortality rate approaching 40%. Treatment options for people infected with A(H7N9) include the use of neuraminidase (NA) inhibitors. However, like other influenza viruses, A(H7N9) can become resistant to these drugs. The use of monoclonal antibodies is a rapidly developing strategy for controlling influenza virus infection. Here we generated a murine monoclonal antibody (3c10-3) directed against the NA of A(H7N9) and show that prophylactic systemic administration of 3c10-3 fully protected mice from lethal challenge with wild-type A/Anhui/1/2013 (H7N9)...
October 3, 2016: Antiviral Research
Yang Yang, Hai-Peng Liu, Qun Yu, Mei-Bing Yang, De-Min Wang, Tian-Wei Jia, Hao-Jie He, Yun He, Hai-Xia Xiao, Suri S Iyer, Zhen-Chuan Fan, Xin Meng, Peng Yu
A new class of S-sialoside Human Serum Albumin (HSA) and Bovine Serum Albumin (BSA) conjugates were prepared to enhance the binding affinity to hemagglutinin (HA) and neuraminidase (NA). The valency of glycoconjugates was controlled by the reaction ratio of the S-sialoside monomer and protein. Hemagglutination inhibition assay showed that these synthetic glycoproteins have higher affinity to HA than the small clusters of sialosides with lower valency, due to multivalent effect and optimized three dimensional presentation of sialosides on the protein platform...
September 28, 2016: Carbohydrate Research
Bernd Salzberger, Barbara Schmidt
The burden of disease of influenza in Germany has been dominated by high rates of complications in elderly patients in years with high circulation of H3N2 viruses after the introduction of the new H1N1 strain in 2009. Human infections with avian influenza viruses occur mostly in China. Due to the potential of reassortment with human strains these cases are monitored closely. The efficacy of neuraminidase inhibitors (NI) has been newly rated. In randomized studies effects on reduction of complications could not be found, although large cohort studies have demonstrated a reduction of mortality in patients treated with vs...
September 2016: Deutsche Medizinische Wochenschrift
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