Abstract:
:Favipiravir (T-705) is a new anti-influenza drug approved for human use in Japan and progressing through Phase 3 clinical trials in the U.S. In addition to its potent inhibitory effects against influenza virus infection, the compound has been shown to be broadly active against RNA viruses from 9 different families, including the Arenaviridae. Several members of the Arenaviridae family of viruses are significant human pathogens that cause viral hemorrhagic fever, a severe systemic syndrome where vascular leak is a cardinal feature. Because arenaviral infections are unlikely to be diagnosed and treated until the illness has progressed to a more advanced state, it is important to understand the effects of the disease state on favipiravir pharmacokinetics (PK) and biodistribution to help guide therapeutic strategy. During acute arenavirus infection in hamsters, we found reduced plasma favipiravir concentrations and altered kinetics of absorption, elimination and time to maximum drug concentration. In addition, the amounts of the favipiravir M1 primary metabolite were higher in the infected animals, suggesting that favipiravir metabolism may favor the formation of this inactive metabolite during viral infection. We also discovered differences in favipiravir and M1 PK parameters associated with arenavirus infection in a number of hamster tissues. Finally, analysis at the individual animal level demonstrated a correlation between reduced plasma favipiravir concentration with increased disease burden as reflected by weight loss and viral load. Our study is the first to show the impact of active viral infection and disease on favipiravir PK and biodistribution, highlighting the need to consider alterations in these parameters when treating individuals with viral hemorrhagic fever of arenavirus or other etiology.
journal_name
Antiviral Resjournal_title
Antiviral researchauthors
Gowen BB,Sefing EJ,Westover JB,Smee DF,Hagloch J,Furuta Y,Hall JOdoi
10.1016/j.antiviral.2015.07.003subject
Has Abstractpub_date
2015-09-01 00:00:00pages
132-7eissn
0166-3542issn
1872-9096pii
S0166-3542(15)00166-7journal_volume
121pub_type
杂志文章abstract::Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne viral disease of humans that affects a wide geographic area of Africa and Eurasia, including Turkey, Iran, Pakistan, Afghanistan and Russia. Since the first detection of CCHF cases in Turkey in 2002, more than 9700 patients have been reported, with an overall mort...
journal_title:Antiviral research
pub_type: 历史文章,杂志文章,评审
doi:10.1016/j.antiviral.2015.12.003
更新日期:2016-02-01 00:00:00
abstract::Compounds were evaluated for antiviral activity in rhabdomyosarcoma (RD) cells against a recent 2014 clinical isolate of enterovirus D68 (EV-D68), a 1962 strain of EV-68D, rhinovirus 87 (RV-87, serologically the same as EV-D68), and enterovirus 71 (EV-71). Test substances included known-active antipicornavirus agents ...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2016.04.003
更新日期:2016-07-01 00:00:00
abstract::Amantadine and rimantadine hydrochloride were tested for stability after storage at different temperatures and under different conditions for extended periods of time. Both compounds were quite stable after storage for at least 25 years at ambient temperature; they both retained full antiviral activity after long-term...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/s0166-3542(98)00015-1
更新日期:1998-06-01 00:00:00
abstract::Suberoylanilide hydroxamic acid (SAHA) has been assessed in clinical trials as part of a "shock and kill" strategy to cure HIV-infected patients. While it was effective at inducing expression of HIV RNA ("shock"), treatment with SAHA did not result in a reduction of reservoir size ("kill"). We therefore utilized a com...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2015.09.002
更新日期:2015-11-01 00:00:00
abstract::The antiviral effect of foscarnet (PFA) on the replication of rotavirus, a member of the Reoviridae, was studied. The pyrophosphate analogue is an effective inhibitor of several viral polymerases acting on the enzyme pyrophosphate binding site. Replication of rotavirus in MA104 cells using different u.o.i. was inhibit...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/0166-3542(94)00085-m
更新日期:1995-05-01 00:00:00
abstract::To identify monoclonal antibodies (mAbs) with high potency and novel recognition sites, more than 25,000 of mouse hybridomas were screened and 4 novel anti-human CCR5 mAbs ROAb12, ROAb13, ROAb14, and ROAb18 showing potent activity in cell-cell fusion (CCF) assay were identified. These mAbs demonstrated potent antivira...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2006.11.003
更新日期:2007-05-01 00:00:00
abstract::Human parainfluenza virus type 3 (HPIV3) is an important respiratory tract pathogen of infants and children. There are no vaccines or antivirals currently approved for prevention or treatment of HPIV3 infection. Towards developing an antiviral therapy to combat HPIV3 infection, we have established a green fluorescent ...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2007.09.001
更新日期:2008-02-01 00:00:00
abstract::DAS181 is an inhaled bacterial sialidase which functions by removing sialic acid (Sia) from the surface of epithelial cells, preventing attachment and subsequent infection by respiratory viruses that utilize Sia as a receptor. DAS181 is typical of bacterial sialidases in cleaving Sia α2-3 and Sia α2-6 linkages, and it...
journal_title:Antiviral research
pub_type: 杂志文章,评审
doi:10.1016/j.antiviral.2013.04.012
更新日期:2013-06-01 00:00:00
abstract::Herpes simplex virus type-1 (HSV-1) causes significant health problems from periodic skin and corneal lesions to encephalitis. It is also considered a cofactor in the development of age-related secondary glaucoma. Inhibition of HSV-1 at the stage of viral entry generates a unique opportunity for preventative and/or th...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2009.07.014
更新日期:2009-10-01 00:00:00
abstract:BACKGROUND:Lactoferrin (LF) is a glycoprotein present in human milk with known antimicrobial effects. In vitro, LF has demonstrated antiviral activity against respiratory syncytial virus (RSV). We sought to assess the effect of bovine (b)LF in RSV replication, lung inflammation and function, cytokine profiles and clini...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2013.05.013
更新日期:2013-08-01 00:00:00
abstract::A major challenge in the development of vaccines against retroviruses is the induction of neutralizing antibodies since they prevent infection of the cells where the virus may persist. The transmembrane envelope (TM) protein contains highly conserved domains and seems to be a suitable target. To study whether vaccinat...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2010.11.011
更新日期:2011-01-01 00:00:00
abstract::A series of four mannose(Man)-, three N-acetylglucosamine (GlcNAc)n-, ten N-acetylgalactosamine/galactose(GalNAc/Gal)-, one 5-acetylneuraminic acid (alpha-2,3-Gal/GalNAc)- and one 5-acetylneuroaminic acid(alpha-2,6-Gal/Gal-NAc)-specific plant agglutinins were evaluated for their antiviral activity in vitro. the mannos...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/0166-3542(92)90038-7
更新日期:1992-06-01 00:00:00
abstract::Rotavirus infection has emerged as an important cause of complications in organ transplantation recipients. Immunosuppressants used to prevent alloreactivity can also interfere with virus infection, but the direct effects of the specific type of immunosuppressants on rotavirus infection are still unclear. Here we prof...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2016.07.017
更新日期:2016-09-01 00:00:00
abstract::The introduction of potent combination therapies in the mid-90s had a tremendous effect on AIDS mortality. However, drug resistance has been a major factor contributing to antiretroviral therapy failure. Currently, there are 26 drugs approved for treating human immunodeficiency virus (HIV) infections, although some of...
journal_title:Antiviral research
pub_type: 杂志文章,评审
doi:10.1016/j.antiviral.2013.01.007
更新日期:2013-04-01 00:00:00
abstract::Lactoferrin (LF), a member of the transferrin family, is a bi-globular protein secreted in milk, saliva, tears, seminal fluid, endocervix and vaginal secretions. LF is an important player in the defence against pathogenic microorganisms and has also been shown to have activity against several viruses including herpesv...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2004.05.005
更新日期:2004-10-01 00:00:00
abstract::Human influenza viruses isolated from Australasia (Australia and New Zealand) and South East Asia were analysed to determine their sensitivity to the NA inhibitor drugs, zanamivir and oseltamivir. A total of 532 strains isolated between 1998 and 2002 were tested using a fluorescence-based assay to measure the relative...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2003.11.008
更新日期:2004-04-01 00:00:00
abstract::In cultured mammalian cells (Vero), different antiviral agents change to differing degrees the ability of HSV2 to down-regulate gap junctions, each agent having a specific effect. Measured by intracellular electrodes, control cell populations showed 49-51% coupling, uninfected populations treated with acyclovir or SDS...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/s0166-3542(02)00106-7
更新日期:2002-11-01 00:00:00
abstract::Currently used antiretroviral therapy is highly successful but there is still a need for new effective and safe prophylactics and therapeutics. We have previously identified and characterized a human engineered antibody domain (eAd), m36, which exhibits potent broadly neutralizing activity against HIV-1 by targeting a...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2010.08.004
更新日期:2010-10-01 00:00:00
abstract::Drug resistance testing has proven its use to guide treatment decisions in HIV-1 infected patients. Genotyping is the preferred technique for clinical drug resistance testing. Many factors complicate the interpretation of mutations towards therapy response, such that an interpretation system is necessary to help the c...
journal_title:Antiviral research
pub_type: 杂志文章,评审
doi:10.1016/j.antiviral.2006.05.003
更新日期:2006-09-01 00:00:00
abstract::Investments in the development of new drugs for orthopoxvirus infections have fostered new avenues of research, provided an improved understanding of orthopoxvirus biology and yielded new therapies that are currently progressing through clinical trials. These broad-based efforts have also resulted in the identificatio...
journal_title:Antiviral research
pub_type: 杂志文章,评审
doi:10.1016/j.antiviral.2012.02.012
更新日期:2012-05-01 00:00:00
abstract::The antiviral activity of antisense oligonucleotides corresponding to different regions of foot-and-mouth disease virus (FMDV) genome has been assessed in BHK-21 cells. The locations of the oligonucleotides used were: (i) two regions within the internal ribosome entry site (IRES), involved in the regulation of the tra...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/0166-3542(93)90082-t
更新日期:1993-09-01 00:00:00
abstract::We have analyzed a panel of protein kinase inhibitors (PKIs) and found that some indolocarbazoles (Gö6976, K252a, K252c) proved to be highly effective inhibitors of GCV-sensitive and -resistant human cytomegalovirus (HCMV) strains, but did not show any effect against herpes simplex virus. Antiviral activity was determ...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/s0166-3542(00)00118-2
更新日期:2000-10-01 00:00:00
abstract::There are no drugs approved specifically to treat disseminated adenovirus (Ad) infections in humans. Cidofovir is active against Ad in cell culture, and it is used frequently in the clinic with disseminated infection in pediatric transplant patients; however, controlled clinical studies have not been conducted to prov...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2014.10.005
更新日期:2014-12-01 00:00:00
abstract::Three water-soluble derivatives of amphotericin B were tested for inhibition of HIV infection in vitro. The compounds amphotericin B methyl ester (AME) and N-(N'-(2-(4'-methylmorpholinio)ethyl)N"-cyclohexyl guanyl) amphotericin B methyl ester (MCG) inhibited HIV infection by 50% at 1 microgram/ml; N-(N'-(3-dimethylami...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/0166-3542(90)90031-2
更新日期:1990-09-01 00:00:00
abstract::Although canine rabies has been eliminated from industrialized countries, infected dogs remain the primary source of human and livestock exposures in Asia, Africa and much of South America. Human deaths are the most important direct economic impact of canine rabies, followed by livestock losses and the cost of PEP, wh...
journal_title:Antiviral research
pub_type: 杂志文章,评审
doi:10.1016/j.antiviral.2013.03.004
更新日期:2013-05-01 00:00:00
abstract::Lentiviral vectors have been shown to be good candidates for gene transfer protocols; however, prevention of insertional mutagenesis remains problematic. Here we report on the design of a conditionally replicating integrase (IN)-defective lentiviral-hybrid episomal vector in which the insertion of the SV40 promoter/or...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2008.06.015
更新日期:2008-12-01 00:00:00
abstract::PMEA [9-[2-(phosphonomethoxy)ethyl]adenine; adefovir] has shown anti-cytomegalovirus activity in animal models and in preliminary human trials. PMEA diphosphate (PMEApp), the active antiviral metabolite of PMEA, is a potent inhibitor of human cytomegalovirus (HCMV) DNA polymerase. PMEA is efficiently taken up and phos...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/s0166-3542(97)00050-8
更新日期:1997-11-01 00:00:00
abstract::Hepatitis C virus (HCV)-specific T cells are key factors in the outcome of acute HCV infection and in protective immunity. This review recapitulates the steps that immunologists have taken in the past 25years to dissect the role of T cell responses in HCV infection. It describes technical as well as disease-specific c...
journal_title:Antiviral research
pub_type: 杂志文章,评审
doi:10.1016/j.antiviral.2014.11.009
更新日期:2015-02-01 00:00:00
abstract::Herpes simplex virus (HSV) types 1 and 2 are ubiquitous organisms that cause infections in human populations throughout the world. The clinical manifestations of HSV infections are varied, ranging from asymptomatic disease to life-threatening illness in neonates and immunocompromised hosts. This article will review th...
journal_title:Antiviral research
pub_type: 杂志文章,评审
doi:10.1016/j.antiviral.2003.09.006
更新日期:2004-02-01 00:00:00
abstract::Vaccination of chickens with herpesvirus of turkey (HVT) confers only partial protection against challenge with a very virulent Marek's disease virus (MDV). Here, we evaluated the ability of recombinant chicken interferon-gamma (rChIFN-γ) to enhance protective efficacy of HVT against the very virulent MDV strain, RB1B...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2011.04.001
更新日期:2011-06-01 00:00:00