CS-8958, a prodrug of the new neuraminidase inhibitor R-125489, shows long-acting anti-influenza virus activity.
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| Abstract |
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.
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| Authors | Makoto Yamashita, Takanori Tomozawa, Masayo Kakuta, Akane Tokumitsu, Hatsumi Nasu, Shuku Kubo |
| Journal | Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 53 Issue 1 Pg. 186-92 (Jan 2009) ISSN: 1098-6596 [Electronic] United States |
| PMID | 18955520 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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