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Noorakmar Jusoh, Hasanuddin Zainal, Azzmer Azzar Abdul Hamid, Noraslinda M Bunnori, Khairul Bariyyah Abd Halim, Shafida Abd Hamid
Recent outbreaks of highly pathogenic influenza strains have highlighted the need to develop new anti-influenza drugs. Here, we report an in silico study of carvone derivatives to analyze their binding modes with neuraminidase (NA) active sites. Two proposed carvone analogues, CV(A) and CV(B), with 36 designed ligands were predicted to inhibit NA (PDB ID: 3TI6) using molecular docking. The design is based on structural resemblance with the commercial inhibitor, oseltamivir (OTV), ligand polarity, and amino acid residues in the NA active sites...
March 15, 2018: Journal of Molecular Modeling
Ken Matsui, Makoto Ozawa, Maki Kiso, Makoto Yamashita, Toshihiko Maekawa, Minoru Kubota, Sumio Sugano, Yoshihiro Kawaoka
Influenza A viruses cause seasonal epidemics and occasional pandemics. The emergence of viruses resistant to neuraminidase (NA) inhibitors and M2 ion channel inhibitors underlines the need for alternate anti-influenza drugs with novel mechanisms of action. Here, we report the discovery of a host factor as a potential target of anti-influenza drugs. By using cell-based virus replication screening of a chemical library and several additional assays, we identified clonidine as a new anti-influenza agent in vitro...
March 15, 2018: Scientific Reports
Nongluk Sriwilaijaroen, Shin-Ichi Nakakita, Sachiko Kondo, Hirokazu Yagi, Koichi Kato, Takeomi Murata, Hiroaki Hiramatsu, Toshio Kawahara, Yohei Watanabe, Yasushi Kanai, Takao Ono, Jun Hirabayashi, Kazuhiko Matsumoto, Yasuo Suzuki
The rapidly evolvable influenza A virus has caused pandemics linked to millions of deaths in the past century. Influenza A viruses are categorized by H (hemagglutinin; HA) and N (neuraminidase; NA) proteins expressed on the viral envelope surface. Analyses of past pandemics suggest that the HA gene segment comes from a nonhuman virus, which is then introduced into an immunologically naïve human population with potentially devastating consequences. As a prerequisite for infection, the nonhuman HA molecules of H1-H16 viruses must be able to bind to specific sialyl receptors on the host cell surface along the human respiratory tract...
March 15, 2018: FEBS Journal
Manoj Kumar, Shanmugasundaram Nagarajan, Harshad V Murugkar, Barnalee Saikia, Bharati Singh, Amit Mishra, Sushil K Tripathi, Sonam Agarwal, Shweta Shukla, Diwakar D Kulkarni, Vijendra Pal Singh, Chakradhar Tosh
H6 subtype avian influenza viruses (AIV), established in terrestrial poultry, have jumped species barriers and caused human infection indicating pandemic potential of the virus. Here, we report isolation, and antigenic and genetic characterization of two H6N2 viruses isolated from apparently healthy domestic ducks in Kerala and Assam, India during 2014 and 2015, respectively. Hemagglutination inhibition assay revealed antigenic divergence between the two isolates. This result was corroborated by amino acid differences at 55 positions (15...
March 9, 2018: Infection, Genetics and Evolution
Artem S Rogovskyy, Sara Lawhon, Kathryn Kuczmanski, David C Gillis, Jing Wu, Helen Hurley, Yuliya V Rogovska, Kranti Konganti, Ching-Yuan Yang, Kay Duncan
Trueperella pyogenes is an opportunistic pathogen that causes suppurative infections in animals including humans. Data on phenotypic and genotypic properties of T. pyogenes isolated from ruminants, particularly goats and sheep, are lacking. We characterized, by phenotypic and genotypic means, T. pyogenes of caprine and ovine origin, and established their phylogenetic relationship with isolates from other ruminants. T. pyogenes isolates ( n = 50) from diagnostic specimens of bovine ( n = 25), caprine ( n = 19), and ovine ( n = 6) origin were analyzed...
March 1, 2018: Journal of Veterinary Diagnostic Investigation
Yuchi Zhang, Yan He, Chengyu Liu, Chunming Liu, Sainan Li
Ultrafiltration liquid chromatography-mass spectrometry (ultrafiltration LC/MS) is introduced as an efficient method that can be applied to rapidly screen and identify ligands from the leaves of Ligustrum lucidum Ait. Using this method, we identified 13 compounds, including organic acids, flavonoids, and glycosides, as potent neuraminidase inhibitors. A continuous online method, employing pressurized liquid extraction followed by parallel centrifugal partition chromatography and preparative liquid chromatography PLE-(parallel-CPC/PLC), was developed for the efficient, scaled-up production of 12 compounds with high purities...
March 6, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Qinhai Ma, Qingtian Yu, Xuefeng Xing, Sinian Liu, Chunyu Shi, Jiabo Luo
The San Wu Huangqin Decoction (SWHD), a traditional Chinese medicine formula, is used to treat colds caused by exposure to wind-pathogen, hyperpyrexia, infectious diseases and cancer; moreover, it is used for detoxification. The individual herbs of SWHD, such as Sophora flavescens and Scutellaria baicalensis , exhibit a wide spectrum of antiviral, anti-inflammatory, antibacterial, anticancer and other properties. The Chinese compound formula of SWHD is composed of S. flavescens, S. baicalensis and Rehmannia glutinosa ...
March 9, 2018: Viruses
Jingjing Jiang, Hongling Wen, Miaomiao Chi, Ying Liu, Jingxue Liu, Zhankui Cao, Li Zhao, Yanyan Song, Na Liu, Lianli Chi, Zhiyu Wang
Human parainfluenza virus type 3 (hPIV3) is an important respiratory pathogen that causes the majority of viral pneumonia of infants and young children. hPIV3 can infect host cells through the synergistic action of hemagglutinin-neuraminidase (HN) protein and the homotypic fusion (F) protein on the viral surface. HN protein plays a variety of roles during the virus invasion process, such as promoting viral particles to bind to receptors, cleaving sialic acid, and activating the F protein. Crystal structure research shows that HN tetramer adopted a "heads-down" conformation, at least two heads dimmer on flank of the four-helix bundle stalk, which forms a symmetrical interaction interface...
March 7, 2018: Virus Genes
Chun-Miao Ji, Bin Wang, Jiyong Zhou, Yao-Wei Huang
A monkey cell line Vero (ATCC CCL-81) is commonly used for porcine epidemic diarrhea virus (PEDV) propagation in vitro. However, it is still controversial whether the porcine aminopeptidase N (pAPN) counterpart on Vero cells (Vero-APN) confers PEDV entry. We found that endogenous expression of Vero-APN was undetectable in the mRNA and the protein levels in Vero cells. We cloned the partial Vero-APN gene (3340-bp) containing exons 1 to 9 from cellular DNA and subsequently generated two APN-knockout Vero cell lines by CRISPR/Cas9 approach...
March 1, 2018: Virology
Hongjing Gu, Yaqian Gao, Shanshan Zhou, Fang Sun, Zhongpeng Zhao, Keyu Wang, Lingna Zhao, Peirui Zhang, Zhaohai Wang, Shaogeng Zhang, Xiliang Wang, Penghui Yang
Human adenoviruses (HAdVs) are prevalent in pediatric and adult patients with severe acute respiratory disease (ARD). To date, there have been no widely used HAdV vaccines available. In this report, we developed a cold-adapted attenuated influenza virus, termed rg HAdV-Flu ca, carrying epitopes from HAdV hexon protein in the backbone of the ca influenza vaccine neuraminidase (NA) gene using reverse genetics. Rg HAdV-Flu ca virus exhibited a cold-adapted (ca) phenotype, and its morphological characteristics were observed using electron microscopy...
March 1, 2018: Antiviral Research
Haixin Ai, Xuewei Wu, Mengyuan Qi, Li Zhang, Huan Hu, Qi Zhao, Jian Zhao, Hongsheng Liu
In recent years, new strains of influenza virus such as H7N9, H10N8, H5N6 and H5N8 had continued to emerge. There was an urgent need for discovery of new anti-influenza virus drugs as well as accurate and efficient large-scale inhibitor screening methods. In this study, we focused on six influenza virus proteins that could be anti-influenza drug targets, including neuraminidase (NA), hemagglutinin (HA), matrix protein 1 (M1), M2 proton channel (M2), nucleoprotein (NP) and non-structural protein 1 (NS1). Structure-based molecular docking was utilized to identify potential inhibitors for these drug targets from 13144 compounds in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform...
March 2, 2018: Interdisciplinary Sciences, Computational Life Sciences
Silke Stertz, W Paul Duprex, Mark Harris
No abstract text is available yet for this article.
March 2018: Journal of General Virology
Jin Jung Kwon, Won-Suk Choi, Ju Hwan Jeong, Eun-Ha Kim, Ok-Jun Lee, Sun-Woo Yoon, Jungwon Hwang, Richard J Webby, Elena A Govorkova, Young Ki Choi, Yun Hee Baek, Min-Suk Song
The resistance of influenza viruses to neuraminidase (NA) inhibitors (NAIs; i.e. oseltamivir, zanamivir, peramivir and laninamivir) can be associated with several NA substitutions, with differing effects on viral fitness. To identify novel molecular markers conferring multi-NAI resistance, the NA gene of oseltamivir-resistant (H275Y, N1 numbering) 2009 pandemic influenza [A(H1N1)pdm09] virus was enriched with random mutations. This randomly mutated viral library was propagated in Madin-Darby canine kidney (MDCK) cells under zanamivir pressure and gave rise to additional changes within NA, including an I436N substitution located outside the NA enzyme active site...
March 2018: Journal of General Virology
Cinzia Colombo, Črtomir Podlipnik, Leonardo Lo Presti, Masahiro Niikura, Andrew J Bennet, Anna Bernardi
The rise of drug-resistant influenza A virus strains motivates the development of new antiviral drugs, with different structural motifs and substitution. Recently, we explored the use of a bicyclic (bicyclo[3.1.0]hexane) analogue of sialic acid that was designed to mimic the conformation adopted during enzymatic cleavage within the neuraminidase (NA; sialidase) active site. Given that our first series of compounds were at least four orders of magnitude less active than available drugs, we hypothesized that the new carbon skeleton did not elicit the same interactions as the cyclohexene frameworks used previously...
2018: PloS One
Han Sol Lee, Ji Yun Noh, Joon Young Song, Hee Jin Cheong, Won Suk Choi, Hye Won Jeong, Seong-Heon Wie, Woo Joo Kim
Influenza A viruses are classified under the Orthomyxoviridae family, and consist of several subtypes, based on their hemagglutinin (HA) and neuraminidase (NA) composition. In some cases, reassortment of the 8 viral RNA segments may occur if different influenza viruses infect the same host, thereby generating new viral strains (antigenic shift). Mutations in the genes of influenza A viruses are enhanced by the absence of RNA proofreading enzymes; in particular, substitutions in the HA protein alter the viral antigenic epitopes sufficiently to avoid the host immune response (antigenic drift)...
February 28, 2018: Influenza and Other Respiratory Viruses
Nobuhisa Ishiguro, Naoko Koseki, Miki Kaiho, Tadashi Ariga, Hideaki Kikuta, Koji Oba, Takehiro Togashi, Keisuke Morita, Akira Inagawa, Akiko Okamura, Shigeru Yamazaki, Satoru Shida, Mutsuko Konno, Nobuaki Kawamura, Akihito Ishizaka, Kimihiko Takada, Keiji Tsubakihara, Naoko Nagano, Mutsuo Shibata, Hideto Furuyama, Yoshihiro Matsuzono, Akemi Koike, Mari Murashita, Yoshio Hatae, Hideki Arioka, Tatsuru Yamanaka, Toru Watanabe, Yuuichi Tabata, Yoshihiro Kumita, Kyosuke Hazama, Yasushi Akutsu, Hayato Aoyagi, Chie Tobise, Katsuki Azuma, Kohichi Yasoshima, Yoko Sawada, Kazuyuki Uetsuji, Akira Tsuchida, Akira Tsuchiyama, Kazue Yasuda, Yasuhisa Odagawa, Mikio Yoshioka
The clinical effectiveness of four neuraminidase inhibitors (NAIs) (oseltamivir, zanamivir, laninamivir, and peramivir) for children aged 0 months to 18 years with influenza A and B were investigated in the 2014-2015 to 2016-2017 influenza seasons in Japan. A total of 1207 patients (747 with influenza A and 460 with influenza B) were enrolled. The Cox proportional-hazards model using all of the patients showed that the duration of fever after administration of the first dose of the NAI was shorter in older patients (hazard ratio = 1...
February 24, 2018: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
M Edward Quach, Wenchun Chen, Renhao Li
Hundreds of billions of platelets are cleared daily from circulation via efficient and highly regulated mechanisms. These mechanisms may be stimulated by exogenous reagents or environmental changes to accelerate platelet clearance, leading to thrombocytopenia. The interplay between anti-apoptotic Bcl-xL and pro-apoptotic molecules Bax and Bak sets an internal clock for the platelet lifespan, and BH3-only proteins, mitochondrial permeabilization, and phosphatidylserine (PS) exposure may also contribute to apoptosis-induced platelet clearance...
February 23, 2018: Blood
Alessandra Gallinaro, Martina Borghi, Roberta Bona, Felicia Grasso, Laura Calzoletti, Laura Palladino, Serena Cecchetti, Maria Fenicia Vescio, Daniele Macchia, Valeria Morante, Andrea Canitano, Nigel Temperton, Maria Rita Castrucci, Mirella Salvatore, Zuleika Michelini, Andrea Cara, Donatella Negri
Viral vectors represent an attractive technology for vaccine delivery. We exploited the integrase defective lentiviral vector (IDLV) as a platform for delivering relevant antigens within the context of the ADITEC collaborative research program. In particular, Influenza virus hemagglutinin (HA) and nucleoprotein (NP) were delivered by IDLVs while H1N1 A/California/7/2009 subunit vaccine (HAp) with or without adjuvant was used to compare the immune response in a murine model of immunization. In order to maximize the antibody response against HA, both IDLVs were also pseudotyped with HA (IDLV-HA/HA and IDLV-NP/HA, respectively)...
2018: Frontiers in Immunology
Murat Gultekin, Ruslan Bayramov, Cagatay Karaca, Niyazi Acer
Sialidosis is a rare lysosomal storage disease caused by neuraminidase gene (NEU1) mutation and a deficiency of the enzyme neuraminidase. The aim of this study was to examine the sialidosis type 1 brain using volumetric magnetic resonance imaging (MRI), diffusion tensor imaging and functional MRI in comparison to 3 controls. The patients gene analysis identified compound heterozygous mutation in the NEU1 that is shown to be associated with the sialidosis type 1. In this very rarely seen case, we found volume changes in different brain structures...
January 2018: Neurosciences: the Official Journal of the Pan Arab Union of Neurological Sciences
Syed M Qadri, David A Donkor, Ishac Nazy, Donald R Branch, William P Sheffield
BACKGROUND: Surface desialylation is associated with erythrocyte aging and mediates phagocytic recognition and clearance of senescent erythrocytes. Neuraminidases, a family of glycohydrolytic enzymes, cleave the glycosidic linkages between sialic acid and mucopolysaccharides and have previously been implicated in erythrocyte dysfunction associated with sepsis. Erythrocytes in septic patients further display a phenotype of accelerated eryptosis characterized by membrane phospholipid scrambling resulting in phosphatidylserine (PS) externalization...
February 17, 2018: European Journal of Haematology
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