In vivo influenza virus-inhibitory effects of the cyclopentane neuraminidase inhibitor RJW-270201Antimicrob Agents Chemother (2001)
AbstractThe cyclopentane inﬂuenza virus neuraminidase inhibitor RWJ-270201 was evaluated against inﬂuenza A/NWS/33 (H1N1), A/Shangdong/09/93 (H3N2), A/Victoria/3/75 (H3N2), and B/Hong Kong/05/72 virus infections in mice. Treatment was by oral gavage twice daily for 5 days beginning 4 h pre-virus exposure. The inﬂuenza virus inhibitor oseltamivir was run in parallel, and ribavirin was included in studies with the A/Shangdong and B/Hong Kong viruses. RWJ-270201 was inhibitory to all infections using doses as low as 1 mg/kg/day. Oseltamivir was generally up to 10-fold less effective than RWJ-270201. Ribavirin was also inhibitory but was less tolerated by the mice at the 75-mg/kg/day dose used. Disease-inhibitory effects included prevention of death, lessening of decline of arterial oxygen saturation, inhibition of lung consolidation, and reduction in lung virus titers. RWJ-270201 and oseltamivir, at doses of 10 and 1 mg/kg/day each, were compared with regard to their effects on daily lung parameters in inﬂuenza A/Shangdong/09/93 virus-infected mice. Maximum virus titer inhibition was seen on day 1, with RWJ-270201 exhibiting the greater inhibitory effect, a titer reduction of >104 cell culture 50% infective doses (CCID50)/g. By day 8, the lung virus titers in mice treated with RWJ-270201 had declined to 101.2 CCID50/g, whereas titers from oseltamivir-treated animals were >103 CCID50/g. Mean lung consolidation was also higher in the oseltamivir-treated animals on day 8. Both neuraminidase inhibitors were well tolerated by the mice. RWJ-270201 was nontoxic at doses as high as 1,000 mg/kg/day. These data indicate potential for the oral use of RWJ-270201 in the treatment of inﬂuenza virus infections in humans.
- Cyclopentane neuramindase,
- influenza virus,
Publication DateJanuary 1, 2001
Citation InformationSidwell, R. W., D. F. Smee, J. H. Huffman, D. L. Barnard, K. W. Bailey, J. D. Morrey, and Y. S. Babu. 2001. In vivo influenza virus-inhibitory effects of the cyclopentane neuraminidase inhibitor RJW-270201. Antimicrob Agents Chemother 45:749-757. PMID11181355 PMCPMC90368