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https://www.readbyqxmd.com/read/28650175/bioactive-peptide-natural-products-as-lead-structures-for-medicinal-use
#1
Tam Dang, Roderich D Süssmuth
The need for new drugs for the treatment of various diseases is enormous. From the previous century until the present, numerous peptide and peptide-derived natural products have been isolated from bacteria and fungi. Hence, microorganisms play a pivotal role as sources for novel drugs with an emphasis on anti-infective agents. Various disciplines from biology, chemistry, and medicine are involved in early stages of the search for peptide natural products including taxonomy, microbiology, bioanalytics, bioinformatics, and medicinal chemistry...
June 26, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28643451/polyclonal-and-monoclonal-b-lymphocytes-response-in-hcv-patients-treated-with-direct-acting-antiviral-agents
#2
Alvise Schiavinato, Alberto Zanetto, Giorgia Pantano, Francesca Tosato, Mitja Nabergoj, Paola Fogar, Elisa Piva, Martina Gambato, Enrica Franceschet, Annarosa Floreani, Fabio Farinati, Patrizia Burra, Francesco Paolo Russo, Mario Plebani
Hepatitis C Virus (HCV) chronic infection can be associated with extrahepatic manifestations such as mixed cryoglobulinemia and lymphoproliferative disorders that are endowed with increased rates of morbidity and all-cause mortality. In this study we used flow cytometry to evaluate the effect of Interferon-free antiviral treatment on peripheral blood lymphocytes in HCV patients with or without associated lymphoproliferative disorders. Flow cytometry analysis of peripheral blood lymphocytes were performed at baseline and at the end of treatment...
June 22, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/28642197/risk-of-hepatocellular-cancer-in-hcv-patients-treated-with-direct-acting-antiviral-agents
#3
Fasiha Kanwal, Jennifer Kramer, Steven M Asch, Maneerat Chayanupatkul, Yumei Cao, Hashem B El-Serag
BACKGROUND AND AIMS: The risk of hepatocellular cancer (HCC) after sustained virological response (SVR) with direct acting antivirals (DAA) is unclear. Our aim was to examine the risk and determinants of HCC in patients cured with DAA. METHODS: We conducted a retrospective cohort study of HCV patients who were treated with DAA in any of the 129 Veterans Health Administration hospitals between 1/1/2015 and 12/31/2015. We calculated the annual incidence rates for HCC by SVR...
June 19, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28636653/the-ebola-virus-vp35-protein-binds-viral-immunostimulatory-and-host-rnas-identified-through-deep-sequencing
#4
Kari A Dilley, Alexander A Voorhies, Priya Luthra, Vinita Puri, Timothy B Stockwell, Hernan Lorenzi, Christopher F Basler, Reed S Shabman
Ebola virus and Marburg virus are members of the Filovirdae family and causative agents of hemorrhagic fever with high fatality rates in humans. Filovirus virulence is partially attributed to the VP35 protein, a well-characterized inhibitor of the RIG-I-like receptor pathway that triggers the antiviral interferon (IFN) response. Prior work demonstrates the ability of VP35 to block potent RIG-I activators, such as Sendai virus (SeV), and this IFN-antagonist activity is directly correlated with its ability to bind RNA...
2017: PloS One
https://www.readbyqxmd.com/read/28627363/effect-of-interferon-based-and-free-therapy-on-early-occurrence-and-recurrence-of-hepatocellular-carcinoma-in-chronic-hepatitis-c
#5
Hiroko Nagata, Mina Nakagawa, Yasuhiro Asahina, Ayako Sato, Yu Asano, Tomoyuki Tsunoda, Masato Miyoshi, Shun Kaneko, Satoshi Otani, Fukiko Kawai-Kitahata, Miyako Murakawa, Sayuri Nitta, Yasuhiro Itsui, Seishin Azuma, Sei Kakinuma, Toshihiko Nouchi, Hideki Sakai, Makoto Tomita, Mamoru Watanabe
BACKGROUND AND AIMS: Although treatment for hepatitis C virus has dramatically improved by the development of direct-acting antiviral agents (DAAs), whether interferon (IFN)-free therapy reduces hepatocarcinogenesis in an equivalent manner to IFN-based therapy remains controversial. The aims of this study were to evaluate the occurrence and recurrence of hepatocellular carcinoma (HCC) in chronic hepatitis C (CHC) patients treated with DAAs and to identify biomarkers of HCC development after antiviral treatment...
June 13, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28622881/discovery-of-%C3%AE-d-2-deoxy-2-dichlorouridine-nucleotide-prodrugs-as-potent-inhibitors-of-hepatitis-c-virus-replication
#6
Pedro Pinho, Genadiy Kalayanov, Hans Westerlind, Åsa Rosenquist, Horst Wähling, Christian Sund, Maria Almeida, Susana Ayesa, Jan Tejbrant, Paul Targett-Adams, Anders Eneroth, Annelie Lindqvist
Discovery of sofosbuvir has radically changed hepatitis C treatment and nucleoside/tide NS5B inhibitors are now viewed as one of the key components in combination therapies with other direct-acting antiviral agents. As part of our program to identify new nucleoside inhibitors of HCV replication, we now wish to report on the discovery of β-d-2'-deoxy-2'-dichlorouridine nucleotide prodrugs as potent inhibitors of HCV replication. Although, cytidine analogues have long been recognized to be metabolized to both cytidine and uridine triphosphates through the action of cytidine deaminase, uridine analogues are generally believed to produce exclusively uridine triphosphate...
May 26, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28622863/down-regulating-heat-shock-protein-27-is-involved-in-porcine-epidemic-diarrhea-virus-escaping-from-host-antiviral-mechanism
#7
Min Sun, Zeyanqiu Yu, Jiale Ma, Zihao Pan, Chengping Lu, Huochun Yao
Porcine epidemic diarrhea virus (PEDV), is the etiological agent of porcine epidemic diarrhea virus (PED), causes high mortality with severe vomiting, diarrhea, and dehydration in swine farms. In this study, the PEDV strain 85-7 could be proliferated effectively in MARC-145 cells, and caused a distinct inhibition of the expression of interferon-β (IFN-β, encoded by IFNB1), which suggested that a full understanding how this virus manipulates the host immune responses is critical in the fight against the spread of PEDV...
June 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28617830/on-treatment-decrease-of-nkg2d-correlates-to-early-emergence-of-clinically-evident-hepatocellular-carcinoma-after-interferon-free-therapy-for-chronic-hepatitis-c
#8
Po-Sung Chu, Nobuhiro Nakamoto, Nobuhito Taniki, Keisuke Ojiro, Takeru Amiya, Yuko Makita, Hiroko Murata, Akihiro Yamaguchi, Shunsuke Shiba, Rei Miyake, Tadashi Katayama, Aya Ugamura, Akihiko Ikura, Karin Takeda, Hirotoshi Ebinuma, Hidetsugu Saito, Takanori Kanai
BACKGROUND AND AIMS: Interferon (IFN)- free direct antiviral agents (DAAs) with rapid HCV eradication might evoke immunological reconstitutions, and some early recurrences of HCC after IFN-free DAAs have been reported. This study aimed to investigate whether natural killer group 2, member D (NKG2D) predicts early emergence of HCC after IFN-free DAAs. METHODS: We conducted a clinical practice-based observational study of 101 patients infected with genotype 1 HCV who received IFN-free (DAAs), and stratified them into those who did or did not develop early (i...
2017: PloS One
https://www.readbyqxmd.com/read/28615303/favouring-modulation-of-circulating-lipoproteins-and-lipid-loading-capacity-by-direct-antiviral-agents-grazoprevir-elbasvir-or-ledipasvir-sofosbuvir-treatment-against-chronic-hcv-infection
#9
Hung-Yu Sun, Pin-Nan Cheng, Chiung-Ying Tseng, Wei-Jen Tsai, Yen-Cheng Chiu, Kung-Chia Young
OBJECTIVE: Lipid homoeostasis is disturbed in patients with HCV infection. Direct-acting antiviral agent (DAA) treatment eradicates chronic HCV viraemia, but the dynamics of lipid components remain elusive. This study investigates the clinical manifestation and mechanistic relevance of plasma triglyceride (TG), cholesterol (Chol), lipoproteins and apolipoproteins (apos) after DAA treatment. DESIGN: Twenty-four patients with chronic genotype 1 (GT1) HCV treated with elbasvir/grazoprevir or ledipasvir/sofosbuvir for 12 weeks, and followed-up thereafter, were recruited...
June 14, 2017: Gut
https://www.readbyqxmd.com/read/28611509/hepatitis-c-in-injection-drug-users-it-is-time-to-treat
#10
EDITORIAL
Alberto Grassi, Giorgio Ballardini
Injection drug users (IDUs) are at risk of hepatitis C virus (HCV) infection, due to needle and syringe sharing. Chronic HCV infection is a major cause of liver-related morbidity and mortality but can be cured with antiviral treatment leading to sustained viral response (SVR). It is well demonstrated that, when close cooperation between specialists in drug addiction and psychiatrists is assured, patients on maintenance treatment with methadone/buprenorphine can be treated for HCV with response rate, tolerability and side effects similar to those reported in non-IDUs...
May 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28611307/review-oncolytic-virotherapy-updates-and-future-directions
#11
REVIEW
Christos Fountzilas, Sukeshi Patel, Devalingam Mahalingam
Oncolytic viruses (OVs) are viral strains that can infect and kill malignant cells while spare their normal counterparts. OVs can access cells through binding to receptors on their surface or through fusion with the plasma membrane and establish a lytic cycle in tumors, while leaving normal tissue essentially unharmed. Multiple viruses have been investigated in humans for the past century. IMLYGIC™ (T-VEC/Talimogene Laherparepvec), a genetically engineered Herpes Simplex Virus, is the first OV approved for use in the United States and the European Union for patients with locally advanced or non-resectable melanoma...
May 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28608619/efficacy-and-safety-of-daclatasvir-based-antiviral-therapy-in-hcv-recurrence-after-liver-transplantation-role-of-cirrhosis-and-genotype-3-a-multi-centre-cohort-study
#12
Magdalena Salcedo, Martín Prieto, Lluís Castells, Juan Manuel Pascasio, Jose Luis Montero Alvarez, Inmaculada Fernández, Gloria Sánchez-Antolín, Luisa González-Diéguez, Miguel García-Gonzalez, Alejandra Otero, Sara Lorente, Maria Dolores Espinosa, Milagros Testillano, Antonio González, Jose Castellote, Fernando Casafont, Maria-Carlota Londoño, Jose Antonio Pons, Esther Molina Pérez, Valentín Cuervas-Mons, Sonia Pascual, Jose Ignacio Herrero, Isidoro Narváez, Carmen Vinaixa, Jordi Llaneras, Jose Manuel Sousa, Rafael Bañares
BACKGROUND & AIMS: Direct-acting antiviral agents (DAA) combining daclatasvir (DCV) have reported good outcomes in the recurrence of hepatitis C virus (HCV) infection after liver transplant (LT). However, its effect on the severe recurrence and the risk of death remains controversial. We evaluated the efficacy, predictors of survival, and safety of DAC-based regimens in a large real-world cohort. METHODS: A total of 331 patients received DCV-based therapy. Duration of therapy and ribavirin use were at the investigator's discretion...
June 13, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28601232/pegylated-interferon-plus-ribavirin-combination-therapy-in-postliver-transplant-recipients-with-recurrent-hepatitis-c-virus-infection
#13
Ta-Ya Lin, Ming-Lun Yeh, Ching-I Huang, Yao-Li Chen, Chia-Yen Dai, Jee-Fu Huang, Zu-Yau Lin, Shinn-Cherng Chen, Chung-Feng Huang, Ming-Lung Yu, Wan-Long Chuang
Posttransplant hepatitis C virus (HCV) recurrence is universal in chronic hepatitis C recipients. Antiviral therapy is suggested after liver transplant to halt disease progression. Pegylated interferon plus ribavirin therapy remains the standard of care in many areas where direct antiviral agents are poorly accessible. This study aimed to assess the treatment efficacy and safety of the regimen for Taiwanese patients with post-transplant HCV recurrence. Nine patients with HCV recurrence postliver transplantation were allocated...
June 2017: Kaohsiung Journal of Medical Sciences
https://www.readbyqxmd.com/read/28590324/is-there-a-relationship-between-treatment-with-direct-antiviral-agents-for-hcv-infection-and-the-development-of-malignancies
#14
Tarek Saadi, Johad Khoury
BACKGROUND AND AIMS: Direct antiviral agents (DAAs) have become the treatment of choice for patients with chronic hepatitis C virus (HCV) infection. As these drugs are new, it is important to learn the adverse events of these drugs in the short and long terms. We report on 7 patients who developed malignancies during treatment with DAAs or a short time after finishing treatment. METHODS: We treated 133 patients with DAAs in our unit between January 2015 and June 2016, 100 (75%) of whom were treated with the combination of paritaprevir/ritonavir/ombitasvir with/without dasabuvir (PrOD)...
June 5, 2017: Journal of Clinical Gastroenterology
https://www.readbyqxmd.com/read/28589085/immune-system-friend-or-foe-of-oncolytic-virotherapy
#15
REVIEW
Anna C Filley, Mahua Dey
Oncolytic viruses (OVs) are an emerging class of targeted anticancer therapies designed to selectively infect, replicate in, and lyse malignant cells without causing harm to normal, healthy tissues. In addition to direct oncolytic activity, OVs have shown dual promise as immunotherapeutic agents. The presence of viral infection and subsequently generated immunogenic tumor cell death trigger innate and adaptive immune responses that mediate further tumor destruction. However, antiviral immune responses can intrinsically limit OV infection, spread, and overall therapeutic efficacy...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28585416/implications-of-hcv-rna-level-at-week-4-of-direct-antiviral-treatments-for-hepatitis-c
#16
Kay Johnson, Pamela K Green, George N Ioannou
We aimed to determine whether the HCV viral load after four weeks of treatment (W4VL) with direct-acting antiviral agents (DAAs) predicts sustained virologic response (SVR) in a real-world clinical setting. We identified 21,095 patients who initiated DAA-based antiviral treatment in the national Veterans Affairs (VA) healthcare system from 01/01/2014 to 06/30/2015. Week 4 viral load was categorized as undetectable, detectable below quantification, detectable above quantification with viral load ≤42 IU/mL and detectable above quantification with viral load > 42 IU/mL...
June 5, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/28579869/management-of-viral-central-nervous-system-infections-a-primer-for-clinicians
#17
REVIEW
P Brandon Bookstaver, Phillip L Mohorn, Ansal Shah, Lauren D Tesh, April M Quidley, Ravish Kothari, Christopher M Bland, Sharon Weissman
Viruses are a common cause of central nervous system (CNS) infections with many host, agent, and environmental factors influencing the expression of viral diseases. Viruses can be responsible for CNS disease through a variety of mechanisms including direct infection and replication within the CNS resulting in encephalitis, infection limited to the meninges, or immune-related processes such as acute disseminated encephalomyelitis. Common pathogens including herpes simplex virus, varicella zoster, and enterovirus are responsible for the greatest number of cases in immunocompetent hosts...
2017: Journal of Central Nervous System Disease
https://www.readbyqxmd.com/read/28579812/cost-per-care-of-the-first-year-of-direct-antiviral-agents-in-the-liguria-region-a-multicenter-analysis
#18
Giovanni Cenderello, Caterina Fanizza, Simona Marenco, Laura Ambra Nicolini, Stefania Artioli, Isabella Baldissarro, Chiara Dentone, Pasqualina De Leo, Antonio Di Biagio
AIMS: Despite the remarkable efficacy shown in clinical practice, concerns have been raised about the costs associated with direct antiviral agent (DAA) therapy. This article presents the real-life costs for DAA treatment sustained by the Italian National Health Service in the Liguria Region (Northern Italy). METHODS: A retrospective analysis of the cost per care sustained for DAA treatment, relating to the period from January 1 to December 31, 2015 in five centers in Liguria was performed...
2017: ClinicoEconomics and Outcomes Research: CEOR
https://www.readbyqxmd.com/read/28579587/direct-acting-antiviral-agents-improved-nephrotic-syndrome-associated-with-refractory-pleural-effusion-and-ascites-caused-by-hepatitis-c-virus-related-nephropathy-a-case-report
#19
Masatoshi Yamato, Kuniaki Arai, Hajime Takatori, Tetsuro Shimakami, Taro Yamashita, Yoshio Sakai, Tatsuya Yamashita, Eishiro Mizukoshi, Masao Honda, Shuichi Kaneko
A 74-year-old man with hepatitis C virus (HCV)-related cirrhosis was admitted because of dyspnea. Laboratory investigations revealed severe proteinuria (4.0g/day), low serum albumin level, and cryoglobulinemia. Computed tomography showed massive pleural effusion and ascites. Because these effusions were leaky and the hepatic reserve was relatively intact, we thought these were mainly caused by nephrotic syndrome. Renal biopsy revealed membranoproliferative glomerulonephritis with mesangial proliferation and excessive matrix deposition...
2017: Nihon Shokakibyo Gakkai Zasshi, the Japanese Journal of Gastro-enterology
https://www.readbyqxmd.com/read/28578865/initiating-hcv-treatment-with-direct-acting-agents-in-opioid-agonist-treatment-when-to-start-for-people-co-infected-with-hiv
#20
Dimitra Panagiotoglou, Emanuel Krebs, Jeong Eun Min, Michelle Olding, Keith Ahamad, Lianping Ti, Julio S G Montaner, Bohdan Nosyk
BACKGROUND: Direct acting antivirals (DAA) raise the possibility of eliminating Hepatitis C virus (HCV) among people who inject drugs (PWID). However, concerns regarding treatment retention and reinfection challenge implementation efforts. Opioid agonist treatment (OAT) provides an opportunity to engage HCV-positive PWID into DAA-based treatment. Our objective was to identify when OAT adherence sufficiently improved to inform DAA initiation in OAT settings, assuming continuous OAT retention for at least twelve weeks is necessary to complete the DAA treatment course...
June 1, 2017: International Journal on Drug Policy
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