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Antiviral Chemistry & Chemotherapy Nov 2002Respiratory syncytial virus (RSV) continues as an emerging infectious disease not only among infants and children, but also for the immune-suppressed, hospitalized and... (Review)
Review
Respiratory syncytial virus (RSV) continues as an emerging infectious disease not only among infants and children, but also for the immune-suppressed, hospitalized and the elderly. To date, ribavirin (Virazole) remains the only therapeutic agent approved for the treatment of RSV. The prophylactic administration of palivizumab is problematic and costly. The quest for an efficacious RSV antiviral has produced a greater understanding of the viral fusion process, a new hypothesis for the mechanism of action of ribavirin, and a promising antisense strategy combining the 2'-5' oligoadenylate antisense (2-5A-antisense) approach and RSV genomics.
Topics: 2',5'-Oligoadenylate Synthetase; Adenine Nucleotides; Adult; Aged; Animals; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antiviral Agents; Child; Child, Preschool; Drug Design; Endoribonucleases; Humans; Infant; Interferons; Membrane Fusion; Mice; Middle Aged; Molecular Structure; Oligodeoxyribonucleotides, Antisense; Oligoribonucleotides; Palivizumab; RNA, Viral; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Ribavirin; Viral Proteins
PubMed: 12718405
DOI: 10.1177/095632020201300601 -
Medecine Et Sante Tropicales 2015
Topics: Antiviral Agents; Female; Humans; Lassa Fever; Pregnancy; Pregnancy Complications, Infectious; Ribavirin
PubMed: 26425737
DOI: No ID Found -
Viruses Jul 2022Heartland bandavirus (HRTV) is an emerging tick-borne virus that is distributed in the United States and that causes febrile illness with thrombocytopenia and...
Susceptibility of Type I Interferon Receptor Knock-Out Mice to Heartland Bandavirus (HRTV) Infection and Efficacy of Favipiravir and Ribavirin in the Treatment of the Mice Infected with HRTV.
Heartland bandavirus (HRTV) is an emerging tick-borne virus that is distributed in the United States and that causes febrile illness with thrombocytopenia and leukocytopenia. It is genetically close to Dabie bandavirus, which is well known as severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV). The mortality rate of human HRTV infection is approximately 10%; however, neither approved anti-HRTV agents nor vaccines exist. An appropriate animal model should be developed to evaluate the efficacy of antiviral agents and vaccines against HRTV. The susceptibility of IFNAR mice with HRTV infection was evaluated using subcutaneous, intraperitoneal, and retro-orbital inoculation routes. IFNAR mice intraperitoneally infected with HRTV showed the most severe clinical signs, and the 50% lethal dose was 3.2 × 10 TCID. Furthermore, to evaluate the utility of a novel lethal IFNAR mice model, IFNAR mice were orally administered favipiravir, ribavirin, or a solvent for 5 days immediately after a lethal dose of HRTV inoculation. The survival rates of the favipiravir-, ribavirin-, and solvent-administered mice were 100, 33, and 0%, respectively. The changes in bodyweights and HRTV RNA loads in the blood of favipiravir-treated IFNAR mice were the lowest among the three groups, which suggests that favipiravir is a promising drug candidate for the treatment of patients with HRTV infection.
Topics: Amides; Animals; Disease Models, Animal; Humans; Mice; Mice, Knockout; Phlebovirus; Pyrazines; Receptor, Interferon alpha-beta; Ribavirin; Solvents; Thrombocytopenia
PubMed: 36016290
DOI: 10.3390/v14081668 -
Journal of Viral Hepatitis Dec 2010By mathematically describing early hepatitis C virus (HCV) RNA decay after initiation of interferon (IFN)-based antiviral therapy, crucial parameters of the in vivo... (Review)
Review
By mathematically describing early hepatitis C virus (HCV) RNA decay after initiation of interferon (IFN)-based antiviral therapy, crucial parameters of the in vivo viral kinetics have been estimated, such as the rate of production and clearance of free virus, and the rate of loss of infected cells. Furthermore, by suggesting mechanisms of action for IFN and ribavirin mathematical modelling has provided a means for evaluating and optimizing treatment strategies. Here, we review recent modelling developments for understanding complex viral kinetics patterns, such as triphasic HCV RNA declines and viral rebounds observed in patients treated with pegylated interferon and ribavirin. Moreover, we discuss new modelling approaches developed to interpret the viral kinetics observed in clinical trials with direct-acting antiviral agents, which induce a rapid decline of wild-type virus but also engender a higher risk for emergence of drug-resistant variants. Lastly, as in vitro systems have allowed a better characterization of the virus lifecycle, we discuss new modelling approaches that combine the intracellular and the extracellular viral dynamics.
Topics: Antiviral Agents; Drug Resistance, Viral; Hepacivirus; Hepatitis C; Humans; Interferon alpha-2; Interferon-alpha; Kinetics; Models, Biological; Polyethylene Glycols; RNA, Viral; Recombinant Proteins; Ribavirin
PubMed: 20723038
DOI: 10.1111/j.1365-2893.2010.01348.x -
Journal of Veterinary Science Nov 2018In many countries, vaccines are used for the prevention of foot-and-mouth disease (FMD). However, because there is no protection against FMD immediately after...
In many countries, vaccines are used for the prevention of foot-and-mouth disease (FMD). However, because there is no protection against FMD immediately after vaccination, research and development on antiviral agents is being conducted to induce protection until immunological competence is produced. This study tested whether well-known chemicals used as RNA virus treatment agents had inhibitory effects on FMD viruses (FMDVs) and demonstrated that ribavirin showed antiviral effects against FMDV . In addition, it was observed that combining the administration of the antiviral agents orally and complementary therapy with vaccines synergistically enhanced antiviral activity and preserved the survival rate and body weight in the experimental animals. Antiviral agents mixed with an adjuvant were inoculated intramuscularly along with the vaccines, thereby inhibiting virus replication after injection and verifying that it was possible to induce early protection against viral infection prior to immunity being achieved through the vaccine. Finally, pigs treated with antiviral agents and vaccines showed no clinical signs and had low virus excretion. Based on these results, it is expected that this combined approach could be a therapeutic and preventive treatment for early protection against FMD.
Topics: Animals; Antiviral Agents; Cell Line; Drug Synergism; Foot-and-Mouth Disease; Foot-and-Mouth Disease Virus; Injections, Intramuscular; Injections, Intraperitoneal; Mice; Mice, Inbred C57BL; Ribavirin; Swine; Swine, Miniature; Viral Vaccines
PubMed: 30304889
DOI: 10.4142/jvs.2018.19.6.788 -
Antimicrobial Agents and Chemotherapy Jul 1991Ribavirin is active in vitro but not in vivo against a number of viruses capable of causing encephalitis. Ribavirin triacetate (RTA), a lipophilic derivative, has been...
Aerosol and intraperitoneal administration of ribavirin and ribavirin triacetate: pharmacokinetics and protection of mice against intracerebral infection with influenza A/WSN virus.
Ribavirin is active in vitro but not in vivo against a number of viruses capable of causing encephalitis. Ribavirin triacetate (RTA), a lipophilic derivative, has been reported to be more effective than ribavirin in protecting animals from encephalitis. By using an influenza A/WSN virus encephalitis model, we demonstrated that RTA administered by small-particle aerosol was able to decrease the death rate and increase the time of survival. To determine if this beneficial effect was due to increased delivery of drug, the pharmacokinetic properties of ribavirin and RTA when administered as an aerosol or by intraperitoneal injection were examined. Aerosol administration of ribavirin or RTA gave significantly higher concentrations of ribavirin in the lungs and serum of mice than did intraperitoneal injection. There was no difference, however, in ribavirin levels when either ribavirin or RTA was administered by small-particle aerosol. In brain tissue, ribavirin concentrations increased with time and did not appear to decrease as rapidly as in lungs and serum. Mean peak ribavirin concentrations in the brain were higher following aerosol administration of ribavirin than RTA, and both were higher than that following intraperitoneal injection of either drug. Administration of ribavirin or RTA by intraperitoneal injection failed to protect mice from a lethal intracerebral inoculation of influenza A/WSN virus, while aerosolized RTA did protect mice. The pharmacokinetics of ribavirin in brain tissue following aerosol administration of either drug did not explain the advantage of RTA over ribavirin in protecting mice from intracerebral infection with influenza A/WSN virus.
Topics: Aerosols; Animals; Brain; Encephalitis; Influenza A virus; Injections, Intraperitoneal; Lung; Mice; Orthomyxoviridae Infections; Ribavirin
PubMed: 1929307
DOI: 10.1128/AAC.35.7.1448 -
Reviews in Medical Virology 2006The nucleoside analogue ribavirin has antiviral activity against many distinct viruses both in vitro and in vivo. Five distinct mechanisms have been proposed to explain... (Review)
Review
The nucleoside analogue ribavirin has antiviral activity against many distinct viruses both in vitro and in vivo. Five distinct mechanisms have been proposed to explain the antiviral properties of ribavirin. These include both indirect mechanisms (inosine monophosphate dehydrogenase inhibition, immunomodulatory effects) and direct mechanisms (interference with RNA capping, polymerase inhibition, lethal mutagenesis). Recent concerns about bioterrorism have renewed interest in exploring the antiviral activity of ribavirin against unique viruses. In this paper, we review the proposed mechanisms of action with emphasis on recent discoveries, as well as the implications of ribavirin resistance. Evidence exists to support each of the five proposed mechanisms of action, and distinct virus/host combinations may preferentially favour one or more of these mechanisms during antiviral therapy.
Topics: Animals; Antiviral Agents; Drug Resistance, Viral; Enzyme Inhibitors; Genome, Viral; Humans; IMP Dehydrogenase; Mutation; RNA Caps; Ribavirin; T-Lymphocytes; Viruses
PubMed: 16287208
DOI: 10.1002/rmv.483 -
Current Opinion in Virology Oct 2014Ribavirin has proven to be effective against several viruses in the clinical setting and a multitude of viruses in vitro. With up to five different proposed mechanisms... (Review)
Review
Ribavirin has proven to be effective against several viruses in the clinical setting and a multitude of viruses in vitro. With up to five different proposed mechanisms of action, recent advances have begun to discern the hierarchy of antiviral effects at play depending on the virus and the host conditions under scrutiny. Studies reveal that for many viruses, antiviral mechanisms may differ depending on cell type in vitro and in vivo. Further analyses are thus required to accurately identify mechanisms to more optimally determine clinical treatments. In recent years, a growing number of ribavirin resistant and sensitive variants have been identified. These variants not only inform on the specific mechanisms by which ribavirin enfeebles the virus, but also can themselves be tools to identify new antiviral compounds.
Topics: Antiviral Agents; Drug Discovery; Drug Resistance, Viral; Humans; Ribavirin; Virus Replication; Viruses
PubMed: 24846716
DOI: 10.1016/j.coviro.2014.04.011 -
PloS One 2011Pathogenic hantaviruses are a closely related group of rodent-borne viruses which are responsible for two distinct diseases in humans, hemorrhagic fever with renal...
Pathogenic hantaviruses are a closely related group of rodent-borne viruses which are responsible for two distinct diseases in humans, hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome (HPS, otherwise known as hantavirus cardiopulmonary syndrome, HCPS). The antiviral effect of ribavirin against Old World hantaviruses, most notably Hantaan virus, is well documented; however, only a few studies have addressed its inhibitory effect on New World hantaviruses. In the present study, we demonstrate that ribavirin is highly active against Andes virus (ANDV), an important etiological agent of HPS, both in vitro and in vivo using a lethal hamster model of HPS. Treatment of ANDV infected Vero E6 cells with ribavirin resulted in dose-dependent reductions in viral RNA and protein as well as virus yields with a half maximal inhibitory concentration between 5 and 12.5 µg ml(-1). In hamsters, treatment with as little as 5 mg kg(-1) day(-1) was 100% effective at preventing lethal HPS disease when therapy was administered by intraperitoneal injection from day 1 through day 10 post-infection. Significant reductions were observed in ANDV RNA and antigen positive cells in lung and liver tissues. Ribavirin remained completely protective when administered by intraperitoneal injections up to three days post-infection. In addition, we show that daily oral ribavirin therapy initiated 1 day post-infection and continuing for ten days is also protective against lethal ANDV disease, even at doses of 5 mg kg(-1) day(-1). Our results suggest ribavirin treatment is beneficial for postexposure prophylaxis against HPS-causing hantaviruses and should be considered in scenarios where exposure to the virus is probable. The similarities between the results obtained in this study and those from previous clinical evaluations of ribavirin against HPS, further validate the hamster model of lethal HPS and demonstrate its usefulness in screening antiviral agents against this disease.
Topics: Administration, Oral; Animals; Antiviral Agents; Chlorocebus aethiops; Cricetinae; Orthohantavirus; Hantavirus Infections; Lung; Mesocricetus; Protein Biosynthesis; RNA, Viral; Ribavirin; Treatment Outcome; Vero Cells; Virus Replication
PubMed: 21853152
DOI: 10.1371/journal.pone.0023560 -
Drug Discoveries & Therapeutics Aug 2013This open-label study assessed the pharmacokinetics of a single 400-mg oral dose of ribavirin in 6 healthy volunteers and 18 subjects with varying degrees of renal...
This open-label study assessed the pharmacokinetics of a single 400-mg oral dose of ribavirin in 6 healthy volunteers and 18 subjects with varying degrees of renal impairment (mild:creatinine clearance [CLcr] 61-90 mL/min/1.73 m², moderate: CLcr 31-60 mL/min/1.73 m(2), severe: CLcr 10-30 mL/min/1.73 m², n = 6 in each group). Blood and urine samples were collected pre-dose and up to 168 hours post-dose for pharmacokinetic analyses. Compared with control subjects, ribavirin area under the plasma concentration-time curve from time zero to the time of the final quantifiable sample (AUC(tf)) and maximum plasma concentration (C(max)) values were increased, and apparent clearance (CL/F), clearance (CLr), and amount excreted (Ae) values were reduced in subjects with renal impairment. Mean ribavirin AUC(tf) was increased 2- to 3-fold in patients with moderate-severe renal impairment compared with control subjects. Ribavirin CL/F and CLr were significantly correlated with CLcr. Single-dose ribavirin was safe and well tolerated in all subjects. The pharmacokinetics of ribavirin were substantially altered in subjects with stable chronic renal impairment, possibly reflecting changes in ribavirin metabolism associated with renal impairment.
Topics: Administration, Oral; Adult; Analysis of Variance; Antiviral Agents; Area Under Curve; Biomarkers; Creatinine; Female; Humans; Kidney; Linear Models; Male; Metabolic Clearance Rate; Middle Aged; Models, Biological; Renal Insufficiency, Chronic; Ribavirin; Severity of Illness Index; Young Adult
PubMed: 24071578
DOI: No ID Found