1. Academic Validation
  2. CS-8958, a prodrug of the new neuraminidase inhibitor R-125489, shows long-acting anti-influenza virus activity

CS-8958, a prodrug of the new neuraminidase inhibitor R-125489, shows long-acting anti-influenza virus activity

  • Antimicrob Agents Chemother. 2009 Jan;53(1):186-92. doi: 10.1128/AAC.00333-08.
Makoto Yamashita 1 Takanori Tomozawa Masayo Kakuta Akane Tokumitsu Hatsumi Nasu Shuku Kubo
Affiliations

Affiliation

  • 1 Biological Research Laboratories IV, Daiichi Sankyo Co Ltd, Hiromachi, Shinagawa, Tokyo, Japan. yamashita.makoto.yr@daiichisankyo.co.jp
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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