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Antimicrobial Agents and Chemotherapy, October 2001, p. 2723-2732, Vol. 45, No. 10
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.
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
*
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.
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