Antiviral research
-
Two new influenza virus neuraminidase inhibitors (NAIs), peramivir and laninamivir, were approved in 2010 which resulted to four NAIs that were used during the 2010-2011 influenza season in Japan. This study aims to monitor the susceptibility of influenza virus isolates in 2009-2010 and 2010-2011 influenza seasons in Japan to the four NAIs using the fluorescence-based 50% inhibitory concentration (IC₅₀) method. Outliers were identified using box-and-whisker plot analysis and full NA gene sequencing was performed to determine the mutations that are associated with reduction of susceptibility to NAIs. ⋯ Among type B viruses, no outliers were identified to the four NAIs. For paired samples that were collected before and after drug treatment, three (3/11; 27.3%) H274Y viruses were identified among A(H1N1)pdm09 viruses after oseltamivir treatment but no outliers were found in the laninamivir-treatment group (n=3). Despite widespread use of NAIs in Japan, the prevalence of NAI-resistant influenza viruses is still low.
-
Severe infections with influenza virus are characterized by acute respiratory distress syndrome (ARDS), a life-threatening disorder in which the alveolocapillary membrane in the lung becomes leaky. This leads to alveolar flooding, hypoxemia and respiratory failure. ⋯ In this paper, we review evidence that lung endothelial activation and vascular leak are a "final common pathway" in severe influenza, as has been reported in bacterial sepsis, and that enhancing endothelial barrier function may improve the outcome of illness. We describe a number of experimental therapies that have shown promise in preventing or reversing increased vascular leak in animal models of sepsis or influenza.
-
Randomized Controlled Trial Multicenter Study Comparative Study
Oseltamivir-zanamivir bitherapy compared to oseltamivir monotherapy in the treatment of pandemic 2009 influenza A(H1N1) virus infections.
The emergence of oseltamivir resistance in 2007 highlighted the need for alternative strategies against influenza. To limit the putative emergence of resistant viruses this clinical trial aimed to evaluate the antiviral efficacy and tolerability of oseltamivir-zanamivir (O+Z) bitherapy compared to oseltamivir monotherapy (O). This clinical trial was designed in 2008-2009 and was conducted during the A(H1N1) influenza virus pandemic in 2009-2010. The A(H1N1)pdm09 viruses were reported to be sensitive to oseltamivir and zanamivir but resistant to amantadine. ⋯ The sample size of our study is too limited to be fully informative and we could not detect whether combination therapy (O+Z) improves or reduces the effectiveness of oseltamivir in the treatment of influenza A(H1N1)pdm09 virus infection in community patients. Additional studies are needed to improve the antiviral treatment of patients infected with influenza virus.
-
The combined effect of rimantadine and oseltamivir in a prophylactic context (therapy beginning 4 h pre-virus infection) and therapeutic context (therapy started at 24 h post-viral inoculation) course on influenza H3N2 virus infection in mice was studied. In the prophylactic course 5 and 10 mg/kg/day rimantadine with 0.2 and 0.4 mg/kg/day (25:1 dose ratio) oseltamivir showed a protection index (PI) of 79.6% and 75%, respectively and a mean survival time (MST) of 13.1 and 12.9 days. The individual effects of the same doses ranged from 0% to 33.3% PI and 8.2 to 10.3 days MST, respectively. ⋯ Monotherapy protection was from 9.1% to a maximum of 56.5%, MST being prolonged only by 1.3-4.2 days compared to 7.5 days in the PBS control group. Lung viral titers were decreased 1445-fold for the most efficacious combination groups and a significant reduction in lung parameters was observed. These data emphasize that prophylactic and therapeutic courses using a combination of oseltamivir and rimantadine have a significant protective effect in mice experimentally infected with drug-sensitive influenza virus A (H3N2).
-
The highly lethal filoviruses, Ebola and Marburg cause severe hemorrhagic fever in humans and non-human primates. To date there are no licensed vaccines or therapeutics to counter these infections. Identifying novel pathways and host targets that play an essential role during infection will provide potential targets to develop therapeutics. ⋯ Investigation of the mechanism of action of the compound revealed that it had antioxidant properties. Specifically, compound NSC 62914 was found to act as a scavenger of reactive oxygen species, and to up-regulate oxidative stress-induced genes. However, four known antioxidant compounds failed to inhibit filovirus infection, thus suggesting that the mechanistic basis of the antiviral function of the antioxidant NSC 62914 may involve modulation of multiple signaling pathways/targets.