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https://www.readbyqxmd.com/read/29909549/pharmacokinetics-of-ombitasvir-paritaprevir-ritonavir-and-dasabuvir-in-healthy-chinese-subjects-and-hcv-gt1b-infected-chinese-south-korean-and-taiwanese-patients
#1
Jiuhong Zha, Bifeng Ding, Haoyu Wang, Weihan Zhao, Chen Yu, Katia Alves, Niloufar Mobashery, Yan Luo, Rajeev M Menon
BACKGROUND/PURPOSE: The 3 direct-acting antiviral (3D) regimen of ombitasvir/paritaprevir/ritonavir plus dasabuvir has recently been approved in several Asian geographic regions for the treatment of hepatitis C virus (HCV) genotype (GT) 1 infection. The pharmacokinetics of the components of the 3D regimen with or without ribavirin were evaluated in healthy Chinese subjects and HCV GT1b-infected Chinese, South Korean, and Taiwanese patients, with or without cirrhosis, to determine how the drug exposures in Asian populations compare with historical data in Western populations...
June 16, 2018: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29908921/il-15-and-ifn-%C3%AE-signal-through-the-erk-pathway-to-inhibit-hcv-replication-independent-of-type-i-ifn-signaling
#2
Fatemeh Vahedi, Amanda J Lee, Susan E Collins, Marianne V Chew, Evan Lusty, Branson Chen, Anisha Dubey, Carl D Richards, Jordan J Feld, Rodney S Russell, Karen L Mossman, Ali A Ashkar
Despite effective new treatments for Hepatitis C virus (HCV) infection, development of drug resistance, safety concerns and cost are remaining challenges. More importantly, there is no vaccine available against hepatitis C infection. Recent data suggest that there is a strong correlation between spontaneous HCV clearance and human NK cell function, particularly IFN-γ production. Further, IL-15 has innate antiviral activity and is also one of the main factors that activates NK cells to produce IFN-γ. To examine whether IL-15 and IFN-γ have direct antiviral activity against HCV, Huh7...
June 13, 2018: Cytokine
https://www.readbyqxmd.com/read/29908447/fas-activity-mediates-airway-inflammation-during-mouse-adenovirus-type-1-respiratory-infection
#3
Laura J Adkins, Caitlyn T Molloy, Jason B Weinberg
CD8 T cells play a key role in clearance of mouse adenovirus type 1 (MAV-1) from the lung and contribute to virus-induced airway inflammation. We tested the hypothesis that interactions between Fas ligand (FasL) and Fas mediate the antiviral and proinflammatory effects of CD8 T cells. FasL and Fas expression were increased in the lungs of C57BL/6 (B6) mice during MAV-1 respiratory infection. Viral replication and weight loss were similar in B6 and Fas-deficient (lpr) mice. Histological evidence of pulmonary inflammation was similar in B6 and lpr mice, but lung mRNA levels and airway proinflammatory cytokine concentrations were lower in MAV-1-infected lpr mice compared to infected B6 mice...
June 13, 2018: Virology
https://www.readbyqxmd.com/read/29908332/enhanced-nanoparticle-uptake-into-virus-infected-cells-could-nanoparticles-be-useful-in-antiviral-therapy
#4
Yasmin Abo-Zeid, Richard A Urbanowicz, Brian J Thomson, William L Irving, Alexander W Tarr, Martin C Garnett
Virus infections cause diseases of different severity ranged from mild infection e.g. common cold into life threating diseases e.g. Human Immunodeficiency virus (HIV), Hepatitis B. Virus infections represent 44% of newly emerging infections. Although there are many efficient antiviral agents, they still have drawbacks due to accumulation at off target organs and developing of virus resistance due to virus mutation. Therefore, developing a delivery system that can selectively target drug into affected organs and avoid off target accumulation would be a highly advantageous strategy to improve antiviral therapy...
June 13, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29908209/the-second-generation-thiazolide-haloxanide-is-a-potent-inhibitor-of-avian-influenza-virus-replication
#5
Simone La Frazia, Sara Piacentini, Anna Riccio, Jean Francois Rossignol, M Gabriella Santoro
The emergence of new avian influenza virus (AIV) strains able to infect humans represents a serious threat to global human health. In addition to surveillance and vaccine development, antiviral therapy remains crucial for AIV control; however, the increase in drug-resistant AIV strains underscores the need for novel approaches to anti-influenza chemotherapy. We have previously shown that the thiazolide anti-infective nitazoxanide (NTZ) inhibits influenza A/PuertoRico/8/1934(H1N1) virus replication, and this effect was associated with inhibition of viral hemagglutinin (HA) maturation...
June 13, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29908044/utilization-and-efficacy-of-elbasvir-grazoprevir-for-treating-hepatitis-c-virus-infection-after-liver-transplantation
#6
Satoshi Miuma, Hisamitsu Miyaaki, Akihiko Soyama, Masaaki Hidaka, Mitsuhisa Takatsuki, Hidetaka Shibata, Naota Taura, Susumu Eguchi, Kazuhiko Nakao
AIM: Recently, elbasvir/grazoprevir combination therapy (EBR/GZR therapy) has been reported to have excellent antiviral effects for chronic genotype 1 hepatitis C virus (HCV) infection. However, it has not been recommended for patients with post-liver transplant (LT) HCV re-infections because of a lack of evidence for effectiveness and drug-drug interactions. METHODS: We report the usage of EBR/GZR in five post-LT HCV re-infected patients with the kinetics of renal function and tacrolimus (Tac) trough levels during and after therapy...
June 16, 2018: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/29907882/relevance-of-placental-type-i-interferon-beta-regulation-for-pregnancy-success
#7
Ja-Young Kwon, Paulomi Aldo, Yuan You, Jiahui Ding, Karen Racicot, Xiaoyan Dong, John Murphy, Guy Glukshtad, Michelle Silasi, Jian Peng, Li Wen, Vikki M Abrahams, Roberto Romero, Gil Mor
Pregnancy is a unique immunologic and microbial condition that requires an adequate level of awareness to provide a fast and protective response against pathogens as well as to maintain a state of tolerance to paternal antigens. Dysregulation of inflammatory pathways in the placenta triggered by pathogens is one of the main factors responsible for pregnancy complications. Type I IFNs are key molecules modulating immune responses at the level of the placenta and are crucial for protection of the pregnancy via their antiviral and immune modulatory properties...
June 15, 2018: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/29907765/dual-functional-peptide-with-defective-interfering-genes-effectively-protects-mice-against-avian-and-seasonal-influenza
#8
Hanjun Zhao, Kelvin K W To, Hin Chu, Qiulu Ding, Xiaoyu Zhao, Cun Li, Huiping Shuai, Shuofeng Yuan, Jie Zhou, Kin-Hang Kok, Shibo Jiang, Kwok-Yung Yuen
Limited efficacy of current antivirals and antiviral-resistant mutations impairs anti-influenza treatment. Here, we evaluate the in vitro and in vivo antiviral effect of three defective interfering genes (DIG-3) of influenza virus. Viral replication is significantly reduced in cell lines transfected with DIG-3. Mice treated with DIG-3 encoded by jetPEI-vector, as prophylaxis and therapeutics against A(H7N7) virus, respectively, have significantly better survivals (80% and 50%) than control mice (0%). We further develop a dual-functional peptide TAT-P1, which delivers DIG-3 with high efficiency and concomitantly exerts antiviral activity by preventing endosomal acidification...
June 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29907366/use-of-ribavirin-in-viruses-other-than-hepatitis-c-a-review-of-the-evidence
#9
German Ramírez-Olivencia, Miriam Estébanez, Francisco Javier Membrillo, Maria Del Carmen Ybarra
Ribavirin is a molecule with antiviral activity against different viruses. In clinical practice, it has made its niche almost exclusively for the treatment of the hepatitisC virus. However, there are other diseases in which it could be of benefit and it has the advantage of being suitable for oral, intravenous and inhaled administration. We conducted a review of the indications of the main drug agencies (Spanish, European and American) and other possible indications, mainly haemorrhagic fevers and coronavirus...
June 12, 2018: Enfermedades Infecciosas y Microbiología Clínica
https://www.readbyqxmd.com/read/29906623/gene-expression-analysis-of-isolated-salmonid-galt-leucocytes-in-response-to-pamps-and-recombinant-cytokines
#10
A Attaya, T Wang, J Zou, T Herath, A Adams, C J Secombes, S Yoon
Increased knowledge of the immune response of the intestine, a physiologically critical organ involved in absorption, secretion and homeostasis in a non-sterile environment, is needed to better understand the mechanisms involved in the induction of long-lasting immunity and, subsequently, the development of efficacious gastrointestinal immunization approaches. To this end, analysis of isolated gut cells will give an insight into the cell types present and their immune capability. Hence, in this study we first optimised a method for salmonid gut leucocyte isolation and characterised the cells on the basis of their expression of a range of selected cell markers associated with T & B cells and dendritic cells...
June 12, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29906476/adar1-affects-hcv-infection-by-modulating-innate-immune-response
#11
Maria Pujantell, Sandra Franco, Iván Galván-Femenía, Roger Badia, Marc Castellví, Edurne Garcia-Vidal, Bonaventura Clotet, Rafael de Cid, Cristina Tural, Miguel A Martínez, Eva Riveira-Muñoz, José A Esté, Ester Ballana
The hepatitis C virus (HCV) is a globally prevalent infectious pathogen. As many as 80% of people infected with HCV do not control the virus and develop a chronic infection. Response to interferon (IFN) therapy is widely variable in chronic HCV infected patients, suggesting that HCV has evolved mechanisms to suppress and evade innate immunity responsible for its control and elimination. Adenosine deaminase acting on RNA 1 (ADAR1) is a relevant factor in the regulation of the innate immune response. The loss of ADAR1 RNA-editing activity and the resulting loss of inosine bases in RNA are critical in producing aberrant RLR-mediated innate immune response, mediated by RNA sensors MDA5 and RIG-I...
June 12, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29906396/synthesis-and-evaluation-of-n-phenyl-3-sulfamoyl-benzamide-derivatives-as-capsid-assembly-modulators-inhibiting-hepatitis-b-virus-hbv
#12
Koen Vandyck, Geert Rombouts, Bart Stoops, Abdellah Tahri, Ann Vos, Wim Verschueren, Yiming Wu, Jingmei Yang, Fuliang Hou, Bing Huang, Karen Vergauwen, Pascale Dehertogh, Jan-Martin Berke, Pierre Jean Marie Bernard Raboisson
Small molecule induced Hepatitis B virus (HBV) capsid assembly modulation is considered an attractive approach for new antiviral therapies against HBV. Here we describe efforts towards the discovery of a HBV capsid assembly modulator in a hit-to-lead optimization, resulting in JNJ-632, a tool compound used to further profile the mode of action. Administration of JNJ-632 (54) in HBV genotype D infected chimeric mice, resulted in a 2.77 log reduction of the HBV DNA viral load.
June 15, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29906392/prodrugs-of-the-phosphoribosylated-forms-of-hydroxypyrazinecarboxamide-pseudobase-t-705-and-its-de-fluoro-analogue-t-1105-as-potent-influenza-virus-inhibitors
#13
Johanna Huchting, Evelien Vanderlinden, Matthias Winkler, Hiba Nasser, Lieve Naesens, Chris Meier
We here disclose chemical synthesis of ribonucleoside 5'-mono- (RMP), -di- (RDP), and -triphosphate (RTP), and cycloSal-, DiPPro-, and TriPPPro-nucleotide-prodrugs of the antiviral pseudobase T-1105. Moreover, we include one nucleoside-diphosphate-prodrug of the chemically less stable T-705. We demonstrate efficient T-1105-RDP- and -RTP-release from the DiPPro- and TriPPPro-compounds by esterase activation. Using crude enzyme extracts, we saw rapid phosphorylation of T-1105-RDP into T-1105-RTP. In sharp contrast, phosphorylation of T-1105-RMP was not seen, indicating a yet unrecognized bottleneck in T-1105's metabolic activation...
June 15, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29906248/foot-and-mouth-disease-virus-nonstructural-protein-2b-interacts-with-cyclophilin-a-modulating-virus-replication
#14
Huisheng Liu, Qiao Xue, Weijun Cao, Fan Yang, Linna Ma, Wenjie Liu, Keshan Zhang, Xiangtao Liu, Zixiang Zhu, Haixue Zheng
Foot-and-mouth disease (FMD) is a highly contagious virus that affects cloven-hoofed animals. To understand better the role of nonstructural protein 2B of the causative agent FMD virus (FMDV) in the process of virus replication, we identified a porcine host protein, cyclophilin A (CypA), which interacts with FMDV 2B. The 2B-CypA interaction was confirmed by coimmunoprecipitation and GST pull-down assays. CypA showed antiviral functions during FMDV infection. Overexpression of CypA decreased FMDV leader protein (Lpro ) and 3A at protein levels...
June 15, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29905492/lrhmgb1-shares-structural-similarities-with-human-hmgb1-and-its-expression-is-induced-in-bacterial-infection-antiviral-vaccination-and-pathogen-associated-molecular-patterns-stimulation
#15
Saswati S Lenka, Mahismita Paichha, Madhubanti Basu, Mrinal Samanta
The high-mobility group box 1 (HMGB1) protein is a highly conserved nonhistone chromosomal protein ubiquitously present in almost all cell types. In the nucleus, it facilitates DNA repair and replication, V(D)J recombination, stabilization of nucleosome, and in the cytoplasm, it regulates autophagy and apoptosis. In addition to these intracellular functions, HMGB1 also facilitates activation of innate immune responses and plays key roles in host defense. To investigate its role in fish, we cloned and characterized HMGB1 in Labeo rohita (LrHMGB1), the most important freshwater fish species in the Indian subcontinent...
June 15, 2018: DNA and Cell Biology
https://www.readbyqxmd.com/read/29904727/retreatment-of-symptomatic-hepatitis-c-virus-genotype-3-associated-mixed-cryoglobulinemia-with-sofosbuvir-and-ribavirin-a-case-report
#16
Dorota Zarębska-Michaluk, Piotr M Stępień, Katarzyna Paluch, Paweł Pabjan
A 52-year-old woman with chronic hepatitis C virus genotype 3 infection developed clinically symptomatic mixed cryoglobulinemia. She started pegylated interferon and ribavirin therapy and in week 12 became negative for HCV RNA with resolution of clinical signs of cryoglobulinemia. The dual treatment was discontinued due to interferon-related bilateral retinopathy. After therapy cessation, relapse of HCV RNA and recurrence of symptomatic cryoglobulinemia were observed. While waiting for the antiviral retreatment option she developed glomerulonephritis with renal impairment...
June 2018: Clinical and Experimental Hepatology
https://www.readbyqxmd.com/read/29904716/data-on-elemental-composition-of-the-medicinal-plant-hymenaea-martiana-hayne-jatob%C3%A3
#17
Layza Sá Rocha, Daniel Araújo Gonçalves, Daniela Granja Arakaki, Paula Fabiana Saldanha Tschinkel, Nayara Vieira de Lima, Lincoln Carlos Silva de Oliveira, Rita de Cássia Avellaneda Guimarães, Valter Aragão do Nascimento
This data article provides elemental compositions profile, determined by inductively coupled plasma-optical emission spectrometry (ICP OES), of the medicinal plant Hymeneaea martiana Hayne which belongs of the family Fabaceae (Leguminosae).It is a tree that demonstrates medicinal purposes as antioxidant, immunomodulatory (Boniface et al., 2017) [1], microbial, antiviral, hepatoprotective, gastroprotective (Almeida et al., 2012) [2] and antifungal (Souza et al., 2010) [3].The content of 13 elements (Al, Ca, Cr, Cu, Fe, K, Mg, Mn, Na, Ni, P, S and Zn) in the barks, leaves, tea leaves and bark tea were detected...
August 2018: Data in Brief
https://www.readbyqxmd.com/read/29904383/influenza-a-virus-facilitates-its-infectivity-by-activating-p53-to-inhibit-the-expression-of-interferon-induced-transmembrane-proteins
#18
Bei Wang, Tze Hau Lam, Mun Kuen Soh, Zhiyong Ye, Jinmiao Chen, Ee Chee Ren
Human influenza virus (IAV) are among the most common pathogens to cause human respiratory infections. A better understanding on interplay between IAV and host factors may provide clues for disease prevention and control. While many viruses are known to downregulate p53 upon entering the cell to reduce the innate host antiviral response, IAV infection is unusual in that it activates p53. However, it has not been clear whether this process has proviral or antiviral effects. In this study, using human isogenic p53 wild-type and p53null A549 cells generated from the CRISPR/Cas9 technology, we observed that p53null cells exhibit significantly reduced viral propagation when infected with influenza A virus (strain A/Puerto Rico/8/1934 H1N1)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29904167/metabolic-conversion-of-ci-1040-turns-a-cellular-mek-inhibitor-into-an-antibacterial-compound
#19
Christin Bruchhagen, Marcel Jarick, Carolin Mewis, Tobias Hertlein, Silke Niemann, Knut Ohlsen, Georg Peters, Oliver Planz, Stephan Ludwig, Christina Ehrhardt
Influenza virus (IV) infections cause severe respiratory illnesses that can be complicated by bacterial super-infections. Previously, we identified the cellular Raf-MEK-ERK cascade as a promising antiviral target. Inhibitors of MEK, such as CI-1040, showed potent antiviral activity. However, it remained unclear if this inhibitor and its active form, ATR-002, might sensitize host cells to either IV or secondary bacterial infections. To address these questions, we studied the anti-pathogen activity of ATR-002 in comparison to CI-1040, particularly, its impact on Staphylococcus aureus (S...
June 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29903906/parkin-negatively-regulates-the-antiviral-signaling-pathway-by-targeting-traf3-for-degradation
#20
Di Xin, Haiyan Gu, Enping Liu, Qinmiao Sun
Chronic neuroinflammation is a characteristic of Parkinson's disease (PD). Previous investigations have shown that Parkin gene mutations are related to the early-onset recessive form of PD and isolated juvenile-onset PD. Further, Parkin plays important roles in mitochondrial quality control and cytokine-induced cell death. However, whether Parkin regulates other cellular events is still largely unknown. In this study, we performed overexpression and knockout experiments, and found that Parkin negatively regulates antiviral immune responses against RNA and DNA viruses...
June 14, 2018: Journal of Biological Chemistry
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