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Titolo:
Characterization of an influenza A (H3N2) virus resistant to the cyclopentane neuraminidase inhibitor RWJ-270201
Autore:
Smee, DF; Sidwell, RW; Morrison, AC; Bailey, KW; Baum, EZ; Ly, L; Wagaman, PC;
Indirizzi:
Utah State Univ, Inst Antiviral Res, Dept Anim Dairy & Vet Sci, Logan, UT 84322 USA Utah State Univ Logan UT USA 84322 m Dairy & Vet Sci, Logan, UT 84322 USA RW Johnson Pharmaceut Res Inst, Raritan, NJ 08869 USA RW Johnson Pharmaceut Res Inst Raritan NJ USA 08869 Raritan, NJ 08869 USA RW Johnson Pharmaceut Res Inst, La Jolla, CA USA RW Johnson Pharmaceut ResInst La Jolla CA USA es Inst, La Jolla, CA USA
Titolo Testata:
ANTIVIRAL RESEARCH
fascicolo: 3, volume: 52, anno: 2001,
pagine: 251 - 259
SICI:
0166-3542(200112)52:3<251:COAIA(>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
4-GUANIDINO-NEU5AC2EN; SENSITIVITY; GENERATION; MICE;
Keywords:
antiviral; neuraminidase inhibitor; influenza virus; drug resistance;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
18
Recensione:
Indirizzi per estratti:
Indirizzo: Smee, DF Utah State Univ, Inst Antiviral Res, Dept Anim Dairy & Vet Sci, Logan, UT 84322 USA Utah State Univ Logan UT USA 84322 Vet Sci, Logan, UT 84322 USA
Citazione:
D.F. Smee et al., "Characterization of an influenza A (H3N2) virus resistant to the cyclopentane neuraminidase inhibitor RWJ-270201", ANTIVIR RES, 52(3), 2001, pp. 251-259

Abstract

The novel influenza virus neurarninidase (NA) inhibitor, (1S,2S,3R,4R)-3-[(1S)-(acetylamino)-2-ethylbutyl]-4-[(aminoiminomethyl)amino]-2-hydroxy-cyclopentanecarboxylic acid (RWJ-270201, BCX-1812), is a potent inhibitor of influenza A and B viruses in cell culture and in infected mice. A mouse-adapted strain of influenza A/Shangdong/09/93 (H3N2) virus was serially passagedin the presence of 1 muM compound. After the fourth passage, breakthrough of resistant virus occurred. By the tenth passage, a twice plaque purified isolate was obtained which could replicate in 10 muM inhibitor. The 50% effective concentration (EC50) values for RWJ-270201 against wild-type and resistant viruses, determined by using a cytopathic effect inhibition assay, were 0.007 and 23 muM, respectively. Cross-resistance to zanamivir and oseltamivir carboxylate was observed. The hemagglutinin (HA) and NA genes of thevirus were sequenced to determine the mutation(s) which conferred drug resistance. No differences were found between the resistant and wild-type viruses in the NA gene. However, a point mutation resulting in a single amino acid change (Lys189Glu) was found in the resistant viral HA. The wild-type and resistant viruses were compared for virulence in BALB/c mice. The resistant virus was approximately tenfold less virulent than the wild-type virus based upon virus challenge dose. Mice infected with a lethal dose of the resistant virus could still be effectively treated with RWJ-270201. Thus, theHA mutation may allow for the spread of the virus in cell culture in the presence of the NA inhibitor, but not in mice. (C) 2001 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/07/20 alle ore 21:07:10