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Antimicrobial Agents and Chemotherapy, October 2001, p. 2723-2732, Vol. 45, No. 10
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.10.2723-2732.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Comparison of Efficacies of RWJ-270201, Zanamivir, and Oseltamivir against H5N1, H9N2, and Other Avian Influenza Viruses

Elena A. Govorkova,1,2 Irina A. Leneva,1,3 Olga G. Goloubeva,4 Karen Bush,5 and Robert G. Webster1,6,*

Departments of Virology and Molecular Biology1 and Biostatistics and Epidemiology,4 St. Jude Children's Research Hospital, and Department of Pathology, University of Tennessee,6 Memphis, Tennessee 38105; The D. I. Ivanovsky Institute of Virology, 123098,2 and Department of Chemotherapy of Infectious Diseases, Russian Chemical and Pharmaceutical Institute, 119815,3 Moscow, Russia; and R. W. Johnson Pharmaceutical Research Institute, Raritan, New Jersey 088695

Received 24 January 2001/Returned for modification 26 April 2001/Accepted 11 July 2001

The orally administered neuraminidase (NA) inhibitor RWJ-270201 was tested in parallel with zanamivir and oseltamivir against a panel of avian influenza viruses for inhibition of NA activity and replication in tissue culture. The agents were then tested for protection of mice against lethal H5N1 and H9N2 virus infection. In vitro, RWJ-270201 was highly effective against all nine NA subtypes. NA inhibition by RWJ-270201 (50% inhibitory concentration, 0.9 to 4.3 nM) was superior to that by zanamivir and oseltamivir carboxylate. RWJ-270201 inhibited the replication of avian influenza viruses of both Eurasian and American lineages in MDCK cells (50% effective concentration, 0.5 to 11.8 µM). Mice given 10 mg of RWJ-270201 per kg of body weight per day were completely protected against lethal challenge with influenza A/Hong Kong/156/97 (H5N1) and A/quail/Hong Kong/G1/97 (H9N2) viruses. Both RWJ-270201 and oseltamivir significantly reduced virus titers in mouse lungs at daily dosages of 1.0 and 10 mg/kg and prevented the spread of virus to the brain. When treatment began 48 h after exposure to H5N1 virus, 10 mg of RWJ-270201/kg/day protected 50% of mice from death. These results suggest that RWJ-270201 is at least as effective as either zanamivir or oseltamivir against avian influenza viruses and may be of potential clinical use for treatment of emerging influenza viruses that may be transmitted from birds to humans.

* Corresponding author. Mailing address: Department of Virology and Molecular Biology, St. Jude Children's Research Hospital, 332 N. Lauderdale Memphis, TN 38105-2794. Phone: (901) 495-3400. Fax: (901) 523-2622. E-mail: Robert.Webster{at}stjude.org.

Antimicrobial Agents and Chemotherapy, October 2001, p. 2723-2732, Vol. 45, No. 10
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.10.2723-2732.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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Copyright © 2001 by the American Society for Microbiology. All rights reserved.