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Antiviral and serology findings
Testing antiviral action against the viruses in mice, the researchers found that the pandemic H1N1 virus was susceptible to licensed neuraminidase inhibitors oseltamivir (Tamiflu) and zanamivir (Relenza), as well as an experimental one called R-125489. An experimental broad-spectrum RNA polymerase inhibitor, called compound T-705, was also effective against the pandemic H1N1 virus
Two neuraminidase (NA) inhibitors, zanamivir (Relenza) and oseltamivir phosphate (Tamiflu), have been licensed for the treatment of and prophylaxis against influenza. In this paper, the new potent NA inhibitor R-125489 is reported for the first time. R-125489 inhibited the NA activities of various type A and B influenza viruses, including subtypes N1 to N9 and oseltamivir-resistant viruses. The survival effect of R-125489 was shown to be similar to that of zanamivir when administered intranasally in a mouse influenza virus A/Puerto Rico/8/34 infection model. Moreover, we found that the esterified form of R-125489 showed improved efficacy compared to R-125489 and zanamivir, depending on the acyl chain length, and that 3-(O)-octanoyl R-125489 (CS-8958) was the best compound in terms of its life-prolonging effect (P < 0.0001, compared to zanamivir) in the same infection model. A prolonged survival effect was observed after a single administration of CS-8958, even if it was given 7 days before infection. It is suggested that intranasally administered CS-8958 works as a long-acting NA inhibitor and shows in vivo efficacy as a result of a single intranasal administration.
T-705, a substituted pyrazine compound, has been found to exhibit potent anti-influenza virus activity in vitro and in vivo. In a time-of-addition study, it was indicated that T-705 targeted an early to middle stage of the viral replication cycle but had no effect on the adsorption or release stage. The anti-influenza virus activity of T-705 was attenuated by addition of purines and purine nucleosides, including adenosine, guanosine, inosine, and hypoxanthine, whereas pyrimidines did not affect its activity. T-705-4-ribofuranosyl-5′-triphosphate (T-705RTP) and T-705-4-ribofuranosyl-5′-monophosphate (T-705RMP) were detected in MDCK cells treated with T-705. T-705RTP inhibited influenza virus RNA polymerase activity in a dose-dependent and a GTP-competitive manner. Unlike ribavirin, T-705 did not have an influence on cellular DNA or RNA synthesis. Inhibition of cellular IMP dehydrogenase by T-705RMP was about 150-fold weaker than that by ribavirin monophosphate, indicating the specificity of the anti-influenza virus activity and lower level of cytotoxicity of T-705. These results suggest that T-705RTP, which is generated in infected cells, may function as a specific inhibitor of influenza virus RNA polymerase and contributes to the selective anti-influenza virus activity of T-705.
WASHINGTON — Nearly a century after history's most lethal flu faded away, survivors' bloodstreams still carry super-potent protection against the 1918 virus, demonstrating the remarkable durability of the human immune system.
Scientists tested the blood of 32 people aged 92 to 102 who were exposed to the 1918 pandemic flu and found antibodies that still roam the body looking to strangle the old flu strain. Researchers manipulated those antibodies into a vaccine and found that it kept alive all the mice they had injected with the killer flu, according to a study published online in the journal Nature.
There's no pressing need for a 1918 flu vaccine because the virus has long since mutated out of its deadly form and is extremely unlikely to be a threat anymore, experts said. What's more important in this research, they said, is that it confirms theories that our immune system has a steel-trap memory.
"It's incredible. The Lord has blessed us with antibodies our whole lifetime," said study co-author Dr. Eric Altschuler ...
Scientists discovered a severe immune system reaction was triggered when mice were infected with the recreated virus.
The US team believes the extreme immune response could have provoked the body to begin killing its own cells, making the flu even deadlier.
The study, published in Nature, may aid the hunt for new treatments. The 1918 pandemic took about 50 million lives.
“The host’s immune system may be overreacting and killing off too many cells”
– Dr John Kash University of Washington
Through functional genomic analysis, they discovered that the mice immune systems responded fiercely to the infection and remained active until the animals’ deaths several days later.
Originally posted by CultureD
www.cidrap.umn.edu...
As well, in addition to Relenza and Tamiflu, there are two novel anti-virals to be used if required:
Antiviral and serology findings
Testing antiviral action against the viruses in mice, the researchers found that the pandemic H1N1 virus was susceptible to licensed neuraminidase inhibitors oseltamivir (Tamiflu) and zanamivir (Relenza), as well as an experimental one called R-125489. An experimental broad-spectrum RNA polymerase inhibitor, called compound T-705, was also effective against the pandemic H1N1 virus
[edit on 14-7-2009 by CultureD]