Activity of ribavirin against Hantaan virus correlates with production of ribavirin-5'-triphosphate, not with inhibition of IMP dehydrogenase.

Abstract:

:Ribavirin (RBV) is a broad-spectrum antiviral agent that inhibits the production of infectious Hantaan virus (HTNV). Although the mechanism of action of RBV against HTNV is not understood, RBV is metabolized in human cells to both RBV-5'-monophosphate, which inhibits IMP dehydrogenase, resulting in a decrease in intracellular GTP levels, and RBV-5'-triphosphate (RBV-TP), which could selectively interact with the viral RNA polymerase. To elucidate which activity of RBV was most important to its anti-HTNV activity, the mechanism of action of RBV was studied in Vero E6 cells. Incubation with 10 to 40 mug/ml RBV resulted in a small decrease in GTP levels that was not dose dependent. Increasing the RBV concentration from 10 to 40 mug/ml resulted in a decrease in viral RNA (vRNA) levels and an increase in RBV-TP formation. Mycophenolic acid (MPA), an inhibitor of IMP dehydrogenase, also resulted in a decrease in vRNA levels; however, treatment with MPA resulted in a much greater decrease in GTP levels than that seen with RBV. Treatment with both MPA and RBV resulted in increased reduction of vRNA levels but did not result in enhanced depression of GTP levels. Although guanosine prevented the depression in GTP levels caused by RBV, guanosine only partially prevented the effect of RBV on vRNA levels. These results suggest that the inhibition of IMP dehydrogenase by RBV is of secondary importance to the inhibition of vRNA replication by RBV and that the interaction of RBV-TP with the viral polymerase is the primary action of RBV.

authors

Sun Y,Chung DH,Chu YK,Jonsson CB,Parker WB

doi

10.1128/AAC.00790-06

subject

Has Abstract

pub_date

2007-01-01 00:00:00

pages

84-8

issue

1

eissn

0066-4804

issn

1098-6596

pii

AAC.00790-06

journal_volume

51

pub_type

杂志文章
  • Antibiotic biosynthesis by cofermentation of blocked mutants of two Micromonospora species.

    abstract::Two aminocyclitol-negative Micromonospora mutants representing two different species, M. purpurea and M. inyoensis, and blocked at different steps in the biosynthetic pathway were paired and cofermented for the synthesis of antibiotics. The two blocked mutants were incapable of producing antibiotics alone except when ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.14.1.73

    authors: Lee BK,Nagabhushan TL,Condon RG,Cooper AB,Waitz JA

    更新日期:1978-07-01 00:00:00

  • Evaluation of antimicrobial activities of clarithromycin and 14-hydroxyclarithromycin against three strains of Haemophilus influenzae by using an in vitro pharmacodynamic model.

    abstract::An in vitro pharmacodynamic model was used to simulate the in vivo pharmacokinetics of clarithromycin and 14-hydroxyclarithromycin in order to generate time-kill curves for three clinical isolates of Haemophilus influenzae (isolates 2019, 91-183, and 1746). Representative concentrations in serum or lung tissue and the...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.38.9.2003

    authors: Walker KJ,Larsson AJ,Zabinski RA,Rotschafer JC

    更新日期:1994-09-01 00:00:00

  • Antibiotic resistance and serotypes of 100 Streptococcus pneumoniae strains isolated in a children's hospital in Barcelona, Spain.

    abstract::A total of 100 Streptococcus pneumoniae strains with various penicillin G susceptibilities, isolated in Barcelona, Spain, from different pediatric sources during 1983 and the first 4 months of 1984, were tested for susceptibility to tetracycline, chloramphenicol, erythromycin, clindamycin, vancomycin, and rifampin. Th...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.28.2.357

    authors: Latorre C,Juncosa T,Sanfeliu I

    更新日期:1985-08-01 00:00:00

  • Identification of a novel clone, ST736, among Enterococcus faecium clinical isolates and its association with daptomycin nonsusceptibility.

    abstract::Resistance to daptomycin in enterococcal clinical isolates remains rare but is being increasingly reported in the United States and worldwide. There are limited data on the genetic relatedness and microbiological and clinical characteristics of daptomycin-nonsusceptible enterococcal clinical isolates. In this study, w...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.02683-14

    authors: Wang G,Kamalakaran S,Dhand A,Huang W,Ojaimi C,Zhuge J,Yee LL,Mayigowda P,Surendraiah PK,Dimitrova N,Fallon JT

    更新日期:2014-08-01 00:00:00

  • Phase 1 safety and pharmacokinetic study of chimeric murine-human monoclonal antibody c alpha Stx2 administered intravenously to healthy adult volunteers.

    abstract::Hemolytic-uremic syndrome (HUS) is a serious complication of infection by Shiga toxin-producing Escherichia coli. Shiga toxin type 2 (Stx2) is responsible for the renal toxicity that can follow intestinal infection and hemorrhagic colitis due to E. coli. A chimeric mouse-human antibody, designated c alpha Stx2, that h...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 临床试验,杂志文章

    doi:10.1128/AAC.49.5.1808-1812.2005

    authors: Dowling TC,Chavaillaz PA,Young DG,Melton-Celsa A,O'Brien A,Thuning-Roberson C,Edelman R,Tacket CO

    更新日期:2005-05-01 00:00:00

  • Broad-spectrum synergistic antiviral activity of selenazofurin and ribavirin.

    abstract::The antiviral effects of selenazofurin (2-beta-D-ribofuranosylselenazole-4-carboxamide, selenazole), ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide), and 3-deazaguanosine (6-amino-1-beta-D-ribofuranosylimidazo-[4.5-C]pyridin-4(5H)-one) were investigated separately and in various combinations in an in v...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.26.4.466

    authors: Kirsi JJ,McKernan PA,Burns NJ 3rd,North JA,Murray BK,Robins RK

    更新日期:1984-10-01 00:00:00

  • Population Pharmacokinetics of Fosfomycin in Critically Ill Patients.

    abstract::This study describes the population pharmacokinetics of fosfomycin in critically ill patients. In this observational study, serial blood samples were taken over several dosing intervals of intravenous fosfomycin treatment. Blood samples were analyzed using a validated liquid chromatography-tandem mass spectrometry tec...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章,多中心研究

    doi:10.1128/AAC.01321-15

    authors: Parker SL,Frantzeskaki F,Wallis SC,Diakaki C,Giamarellou H,Koulenti D,Karaiskos I,Lipman J,Dimopoulos G,Roberts JA

    更新日期:2015-10-01 00:00:00

  • Chlorhexidine resistance in methicillin-resistant Staphylococcus aureus or just an elevated MIC? An in vitro and in vivo assessment.

    abstract::Chlorhexidine (Hibiscrub; ICI) is generally accepted to be effective as an antiseptic hand wash for methicillin-susceptible Staphylococcus aureus (MSSA), but there is dispute whether the chlorhexidine MIC for methicillin-resistant S. aureus (MRSA) strains is higher than that for MSSA strains and, indeed, whether it is...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.35.10.1997

    authors: Cookson BD,Bolton MC,Platt JH

    更新日期:1991-10-01 00:00:00

  • Weakest-Link Dynamics Predict Apparent Antibiotic Interactions in a Model Cross-Feeding Community.

    abstract::With the growing global threat of antimicrobial resistance, novel strategies are required for combatting resistant pathogens. Combination therapy, in which multiple drugs are used to treat an infection, has proven highly successful in the treatment of cancer and HIV. However, this practice has proven challenging for t...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00465-20

    authors: Adamowicz EM,Harcombe WR

    更新日期:2020-10-20 00:00:00

  • Daptomycin-nonsusceptible vancomycin-intermediate staphylococcus aureus vertebral osteomyelitis cases complicated by bacteremia treated with high-dose daptomycin and trimethoprim-sulfamethoxazole.

    abstract::We report two cases of daptomycin (DAP)-nonsusceptible (DNS) vancomycin-intermediate Staphylococcus aureus (VISA) vertebral osteomyelitis cases complicated by bacteremia treated with high-dose daptomycin and trimethoprim-sulfamethoxazole. Both patients responded rapidly and favorably to this combination. The clinical ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01046-12

    authors: Avery LM,Steed ME,Woodruff AE,Hasan M,Rybak MJ

    更新日期:2012-11-01 00:00:00

  • Treatment of bacterial meningitis with ceftizoxime.

    abstract::Ceftizoxime was evaluated in the treatment of 18 patients (6 adults and 12 children) with bacterial meningitis. In seven patients Haemophilus influenzae was the causative agent, in three Neisseria meningitidis, in five Streptococcus pneumoniae, and in one each alpha-streptococcus and Escherichia coli; one case was cul...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.25.2.258

    authors: Overturf GD,Cable DC,Forthal DN,Shikuma C

    更新日期:1984-02-01 00:00:00

  • Comparative in vitro activities of the investigational fluoroquinolone DC-159a and other antimicrobial agents against human mycoplasmas and ureaplasmas.

    abstract::The in vitro susceptibilities of 151 unique clinical isolates of Mycoplasma pneumoniae, Mycoplasma hominis, Mycoplasma fermentans, Mycoplasma genitalium, and Ureaplasma species to DC-159a, an investigational fluoroquinolone, in comparison with those to other agents were determined. Macrolides were the most active agen...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00849-08

    authors: Waites KB,Crabb DM,Duffy LB

    更新日期:2008-10-01 00:00:00

  • Determination of robust ocular pharmacokinetic parameters in serum and vitreous humor of albino rabbits following systemic administration of ciprofloxacin from sparse data sets by using IT2S, a population pharmacokinetic modeling program.

    abstract::Robust determination of the concentration-time profile of anti-infective agents in certain specialized compartments is often limited by the inability to obtain more than a single sample from such a site in any one subject. Vitreous humor and cerebrospinal fluid are obvious examples for which the determination of conce...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.39.8.1683

    authors: Drusano GL,Liu W,Perkins R,Madu A,Madu C,Mayers M,Miller MH

    更新日期:1995-08-01 00:00:00

  • Distribution of tet(H) among Pasteurella isolates from the United States and Canada.

    abstract::Tetracycline-resistant isolates of Pasteurella multocida and Pasteurella haemolytica obtained from various locations in the United States and Canada were studied to determine the distribution of the tet(H) gene. Of the 31 isolates examined, 25 were found to contain the tet(H) gene. Chromosomal or plasmid DNA obtained ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.40.6.1558

    authors: Hansen LM,Blanchard PC,Hirsh DC

    更新日期:1996-06-01 00:00:00

  • Mode of action of lividomycin on protein synthesis in Escherichia coli.

    abstract::Lividomycin specifically inhibited bacterial protein synthesis and had codon misreading activity. Lividomycin, moreover, stimulated the binding of aminoacyl-transfer ribonucleic acid to ribosomes, but did not show any significant effects on the formation of aminoacyl-transfer ribonucleic acid and the puromycin reactio...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.4.3.380

    authors: Yamaguchi M,Eda J,Kobayashi F,Mitsuhashi S

    更新日期:1973-09-01 00:00:00

  • Activities of oral antibiotics on Providencia strains isolated from institutionalized elderly patients with urinary tract infections.

    abstract::More than 250 Providencia strains isolated from the urine of institutionalized elderly patients were tested against cefaclor, cefuroxime, cefetamet, cefpodoxime, ciprofloxacin, and amoxicillin-clavulanic acid. Our results confirm the strong activities of expanded-spectrum oral cephalosporins against Providencia isolat...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.39.12.2819

    authors: Cornaglia G,Frugoni S,Mazzariol A,Piacentini E,Berlusconi A,Fontana R

    更新日期:1995-12-01 00:00:00

  • Bioavailability of tetracycline and doxycycline in fasted and nonfasted subjects.

    abstract::The influence of various test meals and fluid volumes on the relative bioavailability of commercial formulations of doxycycline hyclate and tetracycline hydrochloride was studied in healthy human volunteers. Serum levels of tetracycline were uniformly reduced by approximately 50% by all test meals, whereas serum level...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.11.3.462

    authors: Welling PG,Koch PA,Lau CC,Craig WA

    更新日期:1977-03-01 00:00:00

  • Evernimicin (SCH27899) inhibits a novel ribosome target site: analysis of 23S ribosomal DNA mutants.

    abstract::Spontaneous mutants of susceptible clinical and laboratory isolates of Streptococcus pneumoniae exhibiting reduced susceptibility to evernimicin (SCH27899; MIC, 0.5 to 4.0 mg/liter) were selected on plates containing evernimicin. Four isolates that did not harbor mutations in rplP (which encodes ribosomal protein L16)...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.44.11.3101-3106.2000

    authors: Adrian PV,Mendrick C,Loebenberg D,McNicholas P,Shaw KJ,Klugman KP,Hare RS,Black TA

    更新日期:2000-11-01 00:00:00

  • The Race To Find Antivirals for Zika Virus.

    abstract::Zika virus (ZIKV), a flavivirus transmitted by mosquitoes, was an almost neglected pathogen until its introduction in the Americas in 2015 and its subsequent explosive spread throughout the continent, where it has infected millions of people. The virus has caused social and sanitary alarm, mainly due to its associatio...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章,评审

    doi:10.1128/AAC.00411-17

    authors: Saiz JC,Martín-Acebes MA

    更新日期:2017-05-24 00:00:00

  • Antimicrobial susceptibilities of clinical isolates of HACEK organisms.

    abstract::The "HACEK" organisms are a group of fastidious Gram-negative bacteria that cause a variety of infections, including infective endocarditis. Antimicrobial susceptibility testing is not universally available, and therapy for these infections is often empirical. We report the antimicrobial susceptibilities of 70 clinica...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00111-13

    authors: Coburn B,Toye B,Rawte P,Jamieson FB,Farrell DJ,Patel SN

    更新日期:2013-04-01 00:00:00

  • Comparison of human immunodeficiency virus type 1 tropism profiles in clinical samples by the Trofile and MT-2 assays.

    abstract::The recent availability of CCR5 antagonists as anti-human immunodeficiency virus (anti-HIV) therapeutics has highlighted the need to accurately identify CXCR4-using variants in patient samples when use of this new drug class is considered. The Trofile assay (Monogram Biosciences) has become the method that is the most...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00229-09

    authors: Coakley E,Reeves JD,Huang W,Mangas-Ruiz M,Maurer I,Harskamp AM,Gupta S,Lie Y,Petropoulos CJ,Schuitemaker H,van 't Wout AB

    更新日期:2009-11-01 00:00:00

  • SHV-1 beta-lactamase is mainly a chromosomally encoded species-specific enzyme in Klebsiella pneumoniae.

    abstract::The nature of the SHV-1 beta-lactamase gene was analyzed in 97 epidemiologically unrelated Klebsiella pneumoniae strains isolated from clinical samples. beta-Lactamase bands that focused at a pI of 7.6 (SHV-1-type) in 74 strains, at a pI of 7.1 (LEN-1-type) in 13 strains, and at a pI of 5.4 (TEM-1-type) in 10 strains ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.45.10.2856-2861.2001

    authors: Chaves J,Ladona MG,Segura C,Coira A,Reig R,Ampurdanés C

    更新日期:2001-10-01 00:00:00

  • Evaluation of a System-Specific Function To Describe the Pharmacokinetics of Benzylpenicillin in Term Neonates Undergoing Moderate Hypothermia.

    abstract::The pharmacokinetic (PK) properties of intravenous (i.v.) benzylpenicillin in term neonates undergoing moderate hypothermia after perinatal asphyxia were evaluated, as they have been unknown until now. A system-specific modeling approach was applied, in which our recently developed covariate model describing developme...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.02311-17

    authors: Bijleveld YA,de Haan TR,van der Lee JH,Groenendaal F,Dijk PH,van Heijst A,de Jonge RCJ,Dijkman KP,van Straaten HLM,Rijken M,Zonnenberg IA,Cools F,Zecic A,Nuytemans DHGM,van Kaam AH,Mathôt RAA,PharmaCool Study Group.

    更新日期:2018-03-27 00:00:00

  • Pharmacokinetics of piperaquine transfer into the breast milk of Melanesian mothers.

    abstract::Transfer of piperaquine (PQ) into breast milk was examined in 27 Papua New Guinean women given a 3-day course of dihydroartemisinin-PQ or sulfadoxine-pyrimethamine-PQ during the second/third trimester. Breast milk was sampled on days 1, 2, 3 to 5, 7 to 11, and 14 to 17 postdelivery, a median of 70 days postdose (range...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00327-15

    authors: Moore BR,Salman S,Benjamin J,Page-Sharp M,Yadi G,Batty KT,Siba PM,Mueller I,Davis TM

    更新日期:2015-07-01 00:00:00

  • Optimal sampling schedule design for populations of patients.

    abstract::Generation of pharmacodynamic relationships in the clinical arena requires estimation of pharmacokinetic parameter values for individual patients. When the target population is severely ill, the ability to obtain traditional intensive blood sampling schedules is curtailed. Population modeling guided by optimal samplin...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 临床试验,杂志文章

    doi:10.1128/aac.47.9.2888-2891.2003

    authors: Tam VH,Preston SL,Drusano GL

    更新日期:2003-09-01 00:00:00

  • Antimicrobial resistance in human oral and intestinal anaerobic microfloras.

    abstract::In the present study we determined the resistance patterns of anaerobic bacteria from human saliva and stool specimens and investigated whether there were significant differences in resistance between outpatients and hospitalized patients, regardless of whether they had received antimicrobial agents. No bacterial stra...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.37.8.1665

    authors: Stark CA,Edlund C,Sjöstedt S,Kristensen G,Nord CE

    更新日期:1993-08-01 00:00:00

  • In vitro activity of CP-65,207, a new penem antimicrobial agent, in comparison with those of other agents.

    abstract::CP-65,207 is a new parenteral penem antibiotic with a broad spectrum that includes gram-positive, gram-negative, and anaerobic microorganisms, with MICs for 90% (MIC90s) of the majority of 1,101 clinical pathogens tested being less than or equal to 1 microgram/ml. The compound was from 10- to 100-fold more active than...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.33.8.1160

    authors: Gootz T,Retsema J,Girard A,Hamanaka E,Anderson M,Sokolowski S

    更新日期:1989-08-01 00:00:00

  • Transcriptional regulation of chitin synthases by calcineurin controls paradoxical growth of Aspergillus fumigatus in response to caspofungin.

    abstract::Attenuated activity of echinocandin antifungals at high concentrations, known as the "paradoxical effect," is a well-established phenomenon in Candida albicans and Aspergillus fumigatus. In the yeast C. albicans, upregulation of chitin biosynthesis via the protein kinase C (PKC), high-osmolarity glycerol response (HOG...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00854-09

    authors: Fortwendel JR,Juvvadi PR,Perfect BZ,Rogg LE,Perfect JR,Steinbach WJ

    更新日期:2010-04-01 00:00:00

  • Disposition of caspofungin: role of distribution in determining pharmacokinetics in plasma.

    abstract::The disposition of caspofungin, a parenteral antifungal drug, was investigated. Following a single, 1-h, intravenous infusion of 70 mg (200 microCi) of [(3)H]caspofungin to healthy men, plasma, urine, and feces were collected over 27 days in study A (n = 6) and plasma was collected over 26 weeks in study B (n = 7). Su...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 临床试验,杂志文章

    doi:10.1128/aac.48.3.815-823.2004

    authors: Stone JA,Xu X,Winchell GA,Deutsch PJ,Pearson PG,Migoya EM,Mistry GC,Xi L,Miller A,Sandhu P,Singh R,deLuna F,Dilzer SC,Lasseter KC

    更新日期:2004-03-01 00:00:00

  • Factors impacting unbound vancomycin concentrations in different patient populations.

    abstract::The unbound drug hypothesis states that only unbound drug concentrations are active and available for clearance, and highly variable results regarding unbound vancomycin fractions have been reported in the literature. We have determined the unbound vancomycin fractions in four different patient groups by a liquid chro...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01185-15

    authors: Oyaert M,Spriet I,Allegaert K,Smits A,Vanstraelen K,Peersman N,Wauters J,Verhaegen J,Vermeersch P,Pauwels S

    更新日期:2015-11-01 00:00:00