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virus nonstructural protein

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https://www.readbyqxmd.com/read/29156382/discovery-of-selective-dengue-virus-inhibitors-using-combination-of-molecular-fingerprint-based-virtual-screening-protocols-structure-based-pharmacophore-model-development-molecular-dynamics-simulations-and-in-vitro-studies
#1
Shaher Bano Mirza, Regina Ching Hua Lee, Justin Jang Hann Chu, Ramin Ekhteiari Salmas, Thomas Mavromoustakos, Serdar Durdagi
Dengue virus is a major issue of tropical and sub-tropical regions. The proliferation of virus results in immense number of deaths each year because of unavailability of on-shelf drugs. This issue necessitates the design of novel anti-Dengue drugs. The protease enzyme pathway is the critical target for drug design due to its significance in the replication, survival and other cellular activities of Dengue virus. Keeping in mind the worsening situation regarding Dengue virus, approximately eighteen million drug-like compounds from the ZINC small molecule database have been screened against Nonstructural Protein 3 (NS3) previously by our group...
October 24, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/29152578/middle-east-respiratory-syndrome-coronavirus-nonstructural-protein-16-is-necessary-for-interferon-resistance-and-viral-pathogenesis
#2
Vineet D Menachery, Lisa E Gralinski, Hugh D Mitchell, Kenneth H Dinnon, Sarah R Leist, Boyd L Yount, Rachel L Graham, Eileen T McAnarney, Kelly G Stratton, Adam S Cockrell, Kari Debbink, Amy C Sims, Katrina M Waters, Ralph S Baric
Coronaviruses (CoVs) encode a mixture of highly conserved and novel genes, as well as genetic elements necessary for infection and pathogenesis, raising the possibility of common targets for attenuation and therapeutic design. In this study, we focused on highly conserved nonstructural protein 16 (NSP16), a viral 2'O-methyltransferase (2'O-MTase) that encodes critical functions in immune modulation and infection. Using reverse genetics, we disrupted a key motif in the conserved KDKE motif of Middle East respiratory syndrome CoV (MERS-CoV) NSP16 (D130A) and evaluated the effect on viral infection and pathogenesis...
November 2017: MSphere
https://www.readbyqxmd.com/read/29142571/in-vitro-transcription-analysis-of-ns5a-from-hcv-3a-circulating-in-pakistani-patients-with-chronic-hepatitis-c-and-their-differential-response-to-antiviral-therapy
#3
Shameem Bhatti, Sobia Manzoor, Fahed Parvaiz, Javed Ashraf, Farakh Javed
Objective: Mutations in HCV nonstructural protein 5A (NS5A) play a vital role in virus resistance. The aim of this study was to develop a correlation between NS5A mutations (genotype 3a) and virological response towards interferon alpha (IFN-α) plus ribavirin therapy. Methods: In this study, which was conducted from 09-02-2013 to 25-11-2015 in the rural area of Province Sindh - Pakistan, total patients' responses to peg-IFN therapy were investigated. Patients were given peg-IFN therapy for 24 to 48 weeks and categorized as sustained virologic responders (SVR) or non-responders (NR) to HCV infection...
September 2017: Pakistan Journal of Medical Sciences Quarterly
https://www.readbyqxmd.com/read/29121099/dengue-virus-ns1-cytokine-independent-vascular-leak-is-dependent-on-endothelial-glycocalyx-components
#4
Dustin R Glasner, Kalani Ratnasiri, Henry Puerta-Guardo, Diego A Espinosa, P Robert Beatty, Eva Harris
Dengue virus (DENV) is the most prevalent, medically important mosquito-borne virus. Disease ranges from uncomplicated dengue to life-threatening disease, characterized by endothelial dysfunction and vascular leakage. Previously, we demonstrated that DENV nonstructural protein 1 (NS1) induces endothelial hyperpermeability in a systemic mouse model and human pulmonary endothelial cells, where NS1 disrupts the endothelial glycocalyx-like layer. NS1 also triggers release of inflammatory cytokines from PBMCs via TLR4...
November 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29114026/proofreading-deficient-coronaviruses-adapt-for-increased-fitness-over-long-term-passage-without-reversion-of-exoribonuclease-inactivating-mutations
#5
Kevin W Graepel, Xiaotao Lu, James Brett Case, Nicole R Sexton, Everett Clinton Smith, Mark R Denison
The coronavirus (CoV) RNA genome is the largest among the single-stranded positive-sense RNA viruses. CoVs encode a proofreading 3'-to-5' exoribonuclease within nonstructural protein 14 (nsp14-ExoN) that is responsible for CoV high-fidelity replication. Alanine substitution of ExoN catalytic residues [ExoN(-)] in severe acute respiratory syndrome-associated coronavirus (SARS-CoV) and murine hepatitis virus (MHV) disrupts ExoN activity, yielding viable mutant viruses with defective replication, up to 20-fold-decreased fidelity, and increased susceptibility to nucleoside analogues...
November 7, 2017: MBio
https://www.readbyqxmd.com/read/29110727/the-nonstructural-proteins-of-pneumoviruses-are-remarkably-distinct-in-substrate-diversity-and-specificity
#6
Michael Ribaudo, Sailen Barik
BACKGROUND: Interferon (IFN) inhibits viruses by inducing several hundred cellular genes, aptly named 'interferon (IFN)-stimulated genes' (ISGs). The only two RNA viruses of the Pneumovirus genus of the Paramyxoviridae family, namely Respiratory Syncytial Virus (RSV) and Pneumonia Virus of Mice (PVM), each encode two nonstructural (NS) proteins that share no sequence similarity but yet suppress IFN. Since suppression of IFN underlies the ability of these viruses to replicate in the host cells, the mechanism of such suppression has become an important area of research...
November 6, 2017: Virology Journal
https://www.readbyqxmd.com/read/29098394/serodiagnosis-targeting-nonstructural-protein-4-of-porcine-reproductive-and-respiratory-syndrome-virus
#7
Shengliang Cao, Xinna Cai, Min Tan, Fachao Sun, Yuchao Wang, Yingli Shang, Sidang Liu, Yihong Xiao
Porcine reproductive and respiratory syndrome virus (PRRSV) causes great economic losses to the swine industry worldwide. Typically, an N protein-coated indirect enzyme-linked immunosorbent assay (N-coated iELISA) is used to detect PRRSV antibodies. Non-structural protein (NSP) 4 is essential to the PRRSV life cycle and contains B-cell epitopes. Yet, no specific antibody against NSP4 has been detected in clinical samples. In this study, we developed an NSP4-coated iELISA and compared its effectiveness with the N-coated iELISA...
November 2, 2017: Archives of Virology
https://www.readbyqxmd.com/read/29097641/computer-aided-analysis-of-phytochemicals-as-potential-dengue-virus-inhibitors-based-on-molecular-docking-admet-and-dft-studies
#8
Iqra Qaddir, Nouman Rasool, Waqar Hussain, Sajid Mahmood
BACKGROUND & OBJECTIVES: Dengue fever, caused by dengue virus (DENV), has become a serious threat to human lives. Phytochemicals are known to have great potential to eradicate viral, bacterial and fungal-borne diseases in human beings. This study was aimed at in silico drug development against nonstructural protein 4B (NS4B) of dengue virus 4 (DENV4). METHODS: A total of 2750 phytochemicals from different medicinal plants were selected for this study. These plants grow naturally in the climate of Pakistan and India and have been used for the treatment of various pathologies in human for long-time...
July 2017: Journal of Vector Borne Diseases
https://www.readbyqxmd.com/read/29090410/genomic-analysis-of-a-recombinant-nadc30-like-porcine-reproductive-and-respiratory-syndrome-virus-in-china
#9
Lin-Jian Wang, Bo Wan, Zhenhua Guo, Songlin Qiao, Rui Li, Sha Xie, Xin-Xin Chen, Gaiping Zhang
Recently, NADC30-like porcine reproductive and respiratory syndrome viruses (PRRSVs), which are genetically similar to the NADC30 strain isolated in the United States of America in 2008, have become prevalent in China. Here, a novel variant PRRSV strain named HNhx was successfully isolated on porcine alveolar macrophages from Henan province and the full-length genome sequence was determined. Phylogenetic analysis indicated that HNhx strain was classified into the NADC30-like PRRSV subgroup, in which all the strains had the unique discontinuous 131-amino acid deletion relative to that of the nonstructural protein 2 (Nsp2) of the VR2332 strain...
November 1, 2017: Virus Genes
https://www.readbyqxmd.com/read/29080280/usefulness-of-semiquantitative-pcr-invader-assay-for-selecting-candidates-for-daclatasvir-plus-asunaprevir-combination-therapy-among-patients-with-hepatitis-c-virus-genotype-1b
#10
Koichi Honda, Masataka Seike, Junya Oribe, Mizuki Endo, Mie Arakawa, Masanori Tokoro, Masao Iwao, Tetsu Mori, Junko Nishimura, Yukou Takahashi, Kaoru Omori, Tsutomu Yamashita, Toyokichi Muro, Kazunari Murakami
BACKGROUND & AIMS: PCR-Invader is a highly sensitive assay for detecting nonstructural protein 5A (NS5A) resistance-associated variants (RAVs) of hepatitis C virus (HCV). Here, we validated the accuracy of the semiquantitative PCR-Invader (SQ-PI) assay compared to direct sequencing (DS) for identifying NS5A RAVs, and we evaluated the treatment efficacy of daclatasvir plus asunaprevir (DCV+ASV) for patients judged to be nonpositive for NS5A RAVs by SQ-PI. METHODS: Detection rates of NS5A RAVs by SQ-PI and DS were compared for 204 patients with HCV genotype 1b...
October 28, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/29073030/expanded-subgenomic-mrna-transcriptome-and-coding-capacity-of-a-nidovirus
#11
Han Di, Joseph C Madden, Esther K Morantz, Hsin-Yao Tang, Rachel L Graham, Ralph S Baric, Margo A Brinton
Members of the order Nidovirales express their structural protein ORFs from a nested set of 3' subgenomic mRNAs (sg mRNAs), and for most of these ORFs, a single genomic transcription regulatory sequence (TRS) was identified. Nine TRSs were previously reported for the arterivirus Simian hemorrhagic fever virus (SHFV). In the present study, which was facilitated by next-generation sequencing, 96 SHFV body TRSs were identified that were functional in both infected MA104 cells and macaque macrophages. The abundance of sg mRNAs produced from individual TRSs was consistent over time in the two different cell types...
October 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29070684/ns3-from-hcv-strain-jfh-1-is-an-unusually-robust-helicase-that-is-primed-to-bind-and-unwind-viral-rna
#12
Ting Zhou, Xiaoming Ren, Rebecca L Adams, Anna Marie Pyle
Hepatitis C viruses (HCV) encode a helicase enzyme that is essential for viral replication and assembly (NS3). This helicase has become the focus of extensive basic research on general helicase mechanism and it is also of interest as a novel drug target. Despite the importance of this protein, mechanistic work on NS3 has been conducted almost exclusively on variants from HCV genotype 1. Our understanding of NS3 from the highly active HCV strains that are used to study HCV genetics and mechanism in cell culture (such as JFH-1) is lacking...
October 25, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29037477/mutational-analysis-of-foot-and-mouth-disease-virus-nonstructural-polyprotein-3ab-coding-region-to-design-a-negative-marker-virus
#13
Mukesh Bhatt, Jajati K Mohapatra, Laxmi K Pandey, Nihar N Mohanty, Biswajit Das, Bikash R Prusty, Bramhadev Pattnaik
Inactivated purified whole virus vaccines are used for control of foot and mouth disease (FMD). ELISAs detecting antibodies to the nonstructural proteins (NSP), a marker of infection, are primarily used to differentiate FMD virus (FMDV) infected from vaccinated animals (DIVA). However, such DIVA assays have a limitation to their specificity since residual NSPs present in the relatively impure vaccines are suspected to induce an NSP-antibody response in the repeatedly vaccinated animals. Epitope-deleted negative marker vaccine strategy seems to have an advantage over the conventional vaccines in identifying the infected animals with accuracy...
October 14, 2017: Virus Research
https://www.readbyqxmd.com/read/29028178/zika-virus-immune-evasion-mechanisms-currently-available-therapeutic-regimens-and-vaccines
#14
Arun Asif, Sobia Manzoor, Fatima Tuz-Zahra, Muhammad Saalim, Maliha Ashraf, Javeria Ishtiyaq, Madiha Khalid
The sudden emergence of infectious pathogens such as Zika virus (ZIKV) holds global health concerns. Recent dissemination of ZIKV from Pacific to Americas with an upsurge of congenital anomalies and Guillain Barre Syndrome (GBS) in adults has created an alarming situation. High-throughput studies are in progress to understand ZIKV's mode of pathogenesis and mechanism of immune escape, yet the pathogenesis remains obscure. Mainly ZIKV's envelope (E) protein and nonstructural proteins (mainly NS1 and NS5) manipulate host cell to support viral immune escape by modulation of the interferon pathway and complement antagonism...
October 13, 2017: Viral Immunology
https://www.readbyqxmd.com/read/29021567/classical-swine-fever-virus-nonstructural-protein-p7-modulates-infectious-virus-production
#15
Cheng Zhao, Xiaofang Shen, Rui Wu, Ling Li, Zishu Pan
The classical swine fever virus (CSFV) nonstructural protein p7 is crucial for virus production, yet precisely how the p7 modulates this process is unclear. In this study, we first identified the interactions of p7 with E2 and NS2. The key binding regions of both p7 and NS2 mapped to the first transmembrane (TM1) domain of two proteins. Three amino acid substitutions in the TM1 region of p7 (p7(TDI18/19/20AAA), p7(EVV21/22/23AAA) and p7(YFY25/26/30AAA)) impaired infectious virus production and reduced the interaction of p7 with the NS2 protein...
October 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29016312/dengue-virus-serotype-2-established-in-northern-mozambique-2015-2016
#16
John Oludele, Birgitta Lesko, Isabel Mahumane Gundane, Fernanda de Bruycker-Nogueira, Argentina Muianga, Sadia Ali, Flora Mula, Imelda Chelene, Kerstin I Falk, Flávia Barreto Dos Santos, Eduardo Samo Gudo
After the report of an outbreak of dengue virus serotype 2 in 2014 in Nampula and Pemba cities, northern Mozambique, a surveillance system was established by the National Institute of Health. A study was performed during 2015-2016 to monitor the trend of the outbreak and confirm the circulating serotype of dengue virus (DENV). After the inclusion of consenting patients who met the case definition, samples from 192 patients were tested for the presence of nonstructural protein 1 antigen, and 60/192 (31%) samples were positive...
September 18, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28991178/polyprotein-processing-as-a-determinant-for-in-vitro-activity-of-semliki-forest-virus-replicase
#17
Maija K Pietilä, Irina C Albulescu, Martijn J van Hemert, Tero Ahola
Semliki Forest virus (SFV) is an arthropod-borne alphavirus that induces membrane invaginations (spherules) in host cells. These harbor the viral replication complexes (RC) that synthesize viral RNA. Alphaviruses have four replicase or nonstructural proteins (nsPs), nsP1-4, expressed as polyprotein P1234. An early RC, which synthesizes minus-strand RNA, is formed by the polyprotein P123 and the polymerase nsP4. Further proteolytic cleavage results in a late RC consisting of nsP1-4 and synthesizing plus strands...
October 7, 2017: Viruses
https://www.readbyqxmd.com/read/28988109/nuclear-import-inhibitor-n-4-hydroxyphenyl-retinamide-targets-zika-virus-zikv-nonstructural-protein-5-to-inhibit-zikv-infection
#18
Chunxiao Wang, Sundy N Y Yang, Kate Smith, Jade K Forwood, David A Jans
In the absence of approved therapeutics, Zika virus (ZIKV)'s recent prolific outbreaks in the Americas, together with impacts on unborn fetuses of infected mothers, make it a pressing human health concern worldwide. Although a key player in viral replication in the infected host cell cytoplasm, ZIKV non-structural protein 5 (NS5) appears to contribute integrally to pathogenesis by localising in the host cell nucleus, in similar fashion to NS5 from Dengue virus (DENV). We show here for the first time that ZIKV NS5 is recognized with high nanomolar affinity by the host cell importin α/β1 heterodimer, and that this interaction can be blocked by the novel DENV NS5 targeting inhibitor N-(4-hydroxyphenyl) retinamide (4-HPR)...
December 2, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28978707/prior-dengue-virus-exposure-shapes-t-cell-immunity-to-zika-virus-in-humans
#19
Alba Grifoni, John Pham, John Sidney, Patrick H O'Rourke, Sinu Paul, Bjoern Peters, Sheridan R Martini, Aruna D de Silva, Michael J Ricciardi, Diogo M Magnani, Cassia G T Silveira, Alvino Maestri, Priscilla R Costa, Luzia Maria de-Oliveira-Pinto, Elzinandes Leal de Azeredo, Paulo Vieira Damasco, Elizabeth Phillips, Simon Mallal, Aravinda M de Silva, Matthew Collins, Anna Durbin, Sean A Diehl, Cristhiam Cerpas, Angel Balmaseda, Guillermina Kuan, Josefina Coloma, Eva Harris, James E Crowe, Mars Stone, Phillip J Norris, Michael Busch, Hector Vivanco-Cid, Josephine Cox, Barney S Graham, Julie E Ledgerwood, Lance Turtle, Tom Solomon, Esper G Kallas, David I Watkins, Daniela Weiskopf, Alessandro Sette
While progress has been made in characterizing humoral immunity to Zika virus (ZIKV) in humans, little is known regarding the corresponding T cell responses to ZIKV. Here we investigate the kinetics and viral epitopes targeted by T cells responding to ZIKV and address the critical question of whether pre-existing dengue virus (DENV) T cell immunity modulates these responses. We find that memory T cell responses elicited by prior infection with DENV or vaccination with Tetravalent Dengue Attenuated Vaccines (TDLAV) recognize ZIKV-derived peptides...
October 4, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28977024/rice-stripe-virus-ns3-protein-regulates-primary-mirna-processing-through-association-with-the-mirna-biogenesis-factor-osdrb1-and-facilitates-virus-infection-in-rice
#20
Lijia Zheng, Chao Zhang, Chaonan Shi, Zhirui Yang, Yu Wang, Tong Zhou, Feng Sun, Hong Wang, Shanshan Zhao, Qingqing Qin, Rui Qiao, Zuomei Ding, Chunhong Wei, Lianhui Xie, Jianguo Wu, Yi Li
MicroRNAs (miRNAs) are small regulatory RNAs processed from primary miRNA transcripts, and plant miRNAs play important roles in plant growth, development, and response to infection by microbes. Microbial infections broadly alter miRNA biogenesis, but the underlying mechanisms remain poorly understood. In this study, we report that the Rice stripe virus (RSV)-encoded nonstructural protein 3 (NS3) interacts with OsDRB1, an indispensable component of the rice (Oryza sativa) miRNA-processing complex. Moreover, the NS3-OsDRB1 interaction occurs at the sites required for OsDRB1 self-interaction, which is essential for miRNA biogenesis...
October 2017: PLoS Pathogens
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