Amantadine and ribavirin aerosol treatment of influenza A and B infection in mice

Wilson, Samuel Z.; Knight, Vernon; Wyde, Philip R.; Drake, Stephanie; Couch, R B

doi:10.1128/aac.17.4.642

Cited by 105 publications

(61 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ribavirin, a broad-spectrum antiviral compound, which displays an anti-flu effect, is an example in this respect (Sidwell et al, 1985). (Galegov et al, 1977;Wilson et al, 1980;Hayden et al, 1980Hayden et al, , 1984Hayden, 1986), and with some biological response modifiers: human interferon-α (Hayden et al, 1984), protease inhibitor aprotonin (Zhirnov, 1987) and the antioxidant ionol (4-methyl-2,6-ditretbutylphenol) (Galabov et al, 1994b).…”

Section: Some Authors Noticed a More Rapid Development Of Resistancmentioning

confidence: 99%

Rimantadine and Oseltamivir Demonstrate Synergistic Combination Effect in an Experimental Infection with Type a (H3N2) Influenza Virus in Mice

Galabov

Simeonova

Gegova

2006

Antivir Chem Chemother

View full text Add to dashboard Cite

We studied the combination effect of rimantadine hydrochloride and oseltamivir phosphate on mice infected with influenza A/Aichi/2/68 (H3N2) virus. Compounds were simultaneously administered in a 5-day-treatment course, starting 4 h before intranasal infection with 10 or 20 viral 50% mouse lethal doses. Initially, we tested combinations of oseltamivir (0.05, 0.1 and 0.2 mg/kg/day) and rimantadine (2.5, 5.0 and 7.5 mg/kg/day). Significant differences were recorded between combinationtreated groups, and groups with separately applied compounds and the placebo group, such as: protection index of oseltamivir with 5.0 or 7.5 mg/kg rimantadine varied between 34-41% and 43-87%, respectively, whereas the individual effects of oseltamivir, 5 mg/kg of rimantadine and 7.5 mg/kg of rimantadine were 0-10%, 0% and 18.7-29.6%, respectively; mean survival time in combination-treated groups was lengthened by 3.1-6.9 days, in oseltamivir groups by 0-1.9 days, and in rimantadine groups by 0.8-1.3 days at 5 mg/kg and 2.6-3.2 days at 7.5 mg/kg. The threedimensional method of Prichard and Shipman characterized the combination effect as synergistic. Further, we studied the activity of 0.05 mg/kg/day of oseltamivir combined with 5 mg/kg of rimantadine. Lung virus titre in Madin Darby canine kidney cells, lung index and consolidation score proved the high effectiveness of the combination. When compared with the placebo group, a 2.8 log 10 lower titre of 50% cell culture infectious dose (CCID 50 ) was recorded in the combinationtreated group at 48-60 h post-infection (the peak of lung virus growth). This is in contrast to the 0.1-1.0 log 10 and 1.1-1.4 log 10 reduction in CCID 50 titre observed in the oseltamivir and rimantadine groups, respectively. These data emphasize the high anti-influenza A potential of the combination.

show abstract

Section: Some Authors Noticed a More Rapid Development Of Resistancmentioning

confidence: 99%

Rimantadine and Oseltamivir Demonstrate Synergistic Combination Effect in an Experimental Infection with Type a (H3N2) Influenza Virus in Mice

Galabov

Simeonova

Gegova

2006

Antivir Chem Chemother

View full text Add to dashboard Cite

show abstract

“…Amantadine and its derivative rimantadine have proven to be effective drugs in humans (and mice) for the prevention of influenza, and the drugs are therapeutic for a more rapid resolution of clinical signs and symptoms (3,10,17,39,49,62,69,70). Rimantadine (Flumadine; Forest Pharmaceuticals, Inc.) is licensed by the U.S. Food and Drug Administration for prophylaxis in adults and children and for treatment in adults.…”

mentioning

confidence: 99%

Influenza A Virus M₂Ion Channel Activity Is Essential for Efficient Replication in Tissue Culture

Takeda

Pekosz

Shuck

et al. 2002

J Virol

220

221

View full text Add to dashboard Cite

The discovery that the influenza A virus M 2 protein has proton-selective ion channel activity stemmed from an understanding of the life cycle of influenza virus and the two steps in the life cycle that are inhibited by the antiviral drug amantadine (reviewed in reference 14). Direct evidence that the M 2 protein has a low-pH-activated, proton-selective conductance was obtained by expressing the M 2 protein in oocytes of Xenopus laevis (20,21,47,53,64,65,67) or mammalian cells (6,40,41,66). M 2 -specific cell surface currents were measured, and they were found to be specifically blocked by amantadine. Furthermore, when either peptides corresponding to the M 2 transmembrane (TM) domain or purified M 2 protein was incorporated into planar bilayers, an amantadine-sensitive current was measured (11,36,52,63).Amantadine inhibits the early step of uncoating of influenza virus in endosomes (reviewed in references 14, 31, 32, and 34). When a virion has entered the cell by receptor-mediated endocytosis and the virus particle is in the acidic environment of the endosomal lumen, the M 2 ion channel is activated and conducts protons across the viral membrane. The lowered internal virion pH is thought to weaken protein-protein interactions between the viral matrix protein (M 1 ) and the ribonucleoprotein (RNP) core (4,5,38,72,73; reviewed in reference 18

show abstract

“…Ribavirin (Viratek, ICN Pharmaceuticals, Costa Mesa, CA) was prepared as a 15 mg/ml solution and delivered by small particle aerosol generated by a Collison nebulizer over 18 h, as previously described (10,11).…”

Section: Methodsmentioning

confidence: 99%

Immunoglobulin Administration and Ribavirin Therapy: Efficacy in Respiratory Syncytial Virus Infection of the Cotton Rat

et al. 1987

View full text Add to dashboard Cite

ABSTRACI'. We studied the effects of combined administration of human immunoglobulin (IVIG) and ribavirin aerosol on respiratory syncytial virus (RSV) infection in cotton rats (Sigmodon hispidus). Cotton rats assigned to receive combined therapy were administered Gamimune, a preparation of purified IVIG with a high titer of anti-RSV neutralizing activity, intraperitoneally 24 h prior to intranasal RSV challenge and then treated with ribavirin aerosol 3 days after challenge. Lung viral titers from these cotton rats (geometric mean titers [GMT] loglo = 0.15 f 0.5) were lower than titers from untreated animals (GMT, loglo = 3.7 f 0.6) and animals treated with either IVIG alone (GMT, loglo = 1.8 f 0.9) or ribavirin alone (GMT, loglo = 1.9 f 1.1). Only one of 12 cotton rats treated with both IVIG and ribavirin had a demonstrable titer of virus after RSV challenge. When IVIG administration was delayed until day 3 after virus challenge, lung viral titers were still lowest in animals receiving both IVIG and ribavirin. In comparison, there was no additive antiviral effect between IVIG and ribavirin against RSV infections of HEp-2 cells in vitro. Pathologic changes on histologic examination of pulmonary tissues from animals challenged with RSV were least prominent in animals treated with both IVIG and ribavirin. Despite the apparent absence of in vitro additive antiviral effect, combined use of IVIG and ribavirin was more efficacious against RSV infection in the cotton rat than use of either agent alone. (Pediatr Res 21: 270-274, 1987) Abbreviations RSV, respiratory syncytial virus IVIG, human immunoglobulin TCID50, tissue culture infections doses MEM, minimal essential medium SFU, syncytia forming units PBS, phosphate-buffered saline GMT, geometric mean titers serious RSV disease may require treatment with combinations of currently available therapeutic agents.Previous studies have shown that parenteral inoculation of IVIG containing a high titer of anti-RSV neutralizing activity can provide significant protection in the cotton rat against RSV infection, (3) and significantly reduce the amount of virus shed from the airways of RSV infected owl monkeys (4). Ribavirin( 1 -0-D-ribofuranosyl-1,2,4-triazole-3-carboxamide), a synthetic nucleoside that possesses inhibitory activity against RSV in vitro, has been shown to reduce the amount of RSV in lung tissue of experimentally infected cotton rats (6) and appears to exert a beneficial effect on the course of human RSV infection (7-9). The present study evaluated the combined effect of IVIG and ribavirin on the quantity of RSV contained in lungs of experimentally infected cotton rats and the effect of this combination on histopathologic evidence of infection. METHODSAnimals. Cotton rats (Sigmodon hispidus) used in these studies were derived from two pairs of animals obtained from the Small Animal Section, Veterinary Resources Branch, Division of Research Services, National Institutes of Health. Test animals were 2-3 wk old at the start of each experiment. All animals were m...

show abstract

Amantadine and ribavirin aerosol treatment of influenza A and B infection in mice

Cited by 105 publications

References 10 publications

Rimantadine and Oseltamivir Demonstrate Synergistic Combination Effect in an Experimental Infection with Type a (H3N2) Influenza Virus in Mice

Rimantadine and Oseltamivir Demonstrate Synergistic Combination Effect in an Experimental Infection with Type a (H3N2) Influenza Virus in Mice

Influenza A Virus M₂Ion Channel Activity Is Essential for Efficient Replication in Tissue Culture

Immunoglobulin Administration and Ribavirin Therapy: Efficacy in Respiratory Syncytial Virus Infection of the Cotton Rat

Contact Info

Product

Resources

About

Amantadine and ribavirin aerosol treatment of influenza A and B infection in mice

Cited by 105 publications

References 10 publications

Rimantadine and Oseltamivir Demonstrate Synergistic Combination Effect in an Experimental Infection with Type a (H3N2) Influenza Virus in Mice

Rimantadine and Oseltamivir Demonstrate Synergistic Combination Effect in an Experimental Infection with Type a (H3N2) Influenza Virus in Mice

Influenza A Virus M2Ion Channel Activity Is Essential for Efficient Replication in Tissue Culture

Immunoglobulin Administration and Ribavirin Therapy: Efficacy in Respiratory Syncytial Virus Infection of the Cotton Rat

Contact Info

Product

Resources

About

Influenza A Virus M₂Ion Channel Activity Is Essential for Efficient Replication in Tissue Culture