Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
ORAL-ADMINISTRATION OF A PRODRUG OF THE INFLUENZA-VIRUS NEURAMINIDASEINHIBITOR GS-4071 PROTECTS MICE AND FERRETS AGAINST INFLUENZA INFECTION
Autore:
MENDEL DB; TAI CY; ESCARPE PA; LI WX; SIDWELL RW; HUFFMAN JH; SWEET C; JAKEMAN KJ; MERSON J; LACY SA; LEW W; WILLIAMS MA; ZHANG LJ; CHEN MS; BISCHOFBERGER N; KIM CU;
Indirizzi:
GILEAD SCI INC,333 LAKESIDE DR FOSTER CITY CA 94404 UTAH STATE UNIV,INST ANTIVIRAL RES LOGAN UT 84322 UNIV BIRMINGHAM,SCH BIOL SCI BIRMINGHAM B15 2TT W MIDLANDS ENGLAND PFIZER LTD,CENT RES SANDWICH CT13 9NJ KENT ENGLAND
Titolo Testata:
Antimicrobial agents and chemotherapy
fascicolo: 3, volume: 42, anno: 1998,
pagine: 640 - 646
SICI:
0066-4804(1998)42:3<640:OOAPOT>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
GG167 ANIDINO-2,4-DIDEOXY-2,3-DEHYDRO-N-ACETYLNEURAMINIC; SIALIC-ACID; IN-VITRO; REPLICATION; COMPLEX; SELENAZOFURIN; CATALYSIS; BINDING; GROWTH; ASSAY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
47
Recensione:
Indirizzi per estratti:
Citazione:
D.B. Mendel et al., "ORAL-ADMINISTRATION OF A PRODRUG OF THE INFLUENZA-VIRUS NEURAMINIDASEINHIBITOR GS-4071 PROTECTS MICE AND FERRETS AGAINST INFLUENZA INFECTION", Antimicrobial agents and chemotherapy, 42(3), 1998, pp. 640-646

Abstract

We have recently described GS 4071, a carbocyclic transition-state analog inhibitor of the influenza virus neuraminidase, which has potent inhibitory activity comparable to that of 4-guanidino-Neu5Ac2en (GG167; zanamivir) when tested against influenza A virus replication and neuraminidase activity in vitro. We now report that GS 4071 is active against several strains of influenza A and B viruses in vitro and that oral GS 4101, an ethyl ester prodrug which is converted to GS 4071 in vivo, is active in the mouse and ferret models of influenza virus infection. Oral administration of 10 mg of GS 4104 per kg of body weight perday caused a 100-fold reduction in lung homogenate viral titers and enhanced survival in mice infected with influenza A or B viruses. In ferrets, a 25-mg/kg dose of GS 4104 given twice daily reduced peak viraltiters in nasal washings and eliminated constitutional responses to influenza virus infection including fever, increased nasal signs (sneezing, nasal discharge, mouth breathing), and decreased activity. Consistent with our demonstration that the parent compound is highly specific for influenza virus neuraminidases, no significant drug-related toxicity was observed after the administration of oral dosages of GS 4104 of up to 800 mg/kg/day for 14 days in nonclinical toxicology studies with rats. These results indicate that GS 4101 is a novel, orally active antiviral agent with the potential to be used for the prophylaxis and treatment of influenza A and B virus infections.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 07/07/20 alle ore 11:46:09