H2N2V1, Main, Exploration, bibRecord, 001927

The neuraminidase inhibitor GS4104 (oseltamivir phosphate) is efficacious against A/Hong Kong/156/97 (H5N1) and A/Hong Kong/1074/99 (H9N2) influenza viruses

Identifieur interne : 001927 ( Main/Exploration ); précédent : 001926; suivant : 001928

The neuraminidase inhibitor GS4104 (oseltamivir phosphate) is efficacious against A/Hong Kong/156/97 (H5N1) and A/Hong Kong/1074/99 (H9N2) influenza viruses

Auteurs : Irina A. Leneva [États-Unis] ; Noel Roberts [Royaume-Uni] ; Elena A. Govorkova [États-Unis] ; Olga G. Goloubeva [États-Unis] ; Robert G. Webster [États-Unis]

Source :

Antiviral Research [ 0166-3542 ] ; 2000.

RBID : ISTEX:8F4CD05A5286EB197D517A5B547ADA1B8BFDF728

English descriptors

KwdEn :
- Antiviral agents, Avian influenza viruses, Human influenza A viruses.
Teeft :
- Agents chemother, Amantadine, Anti6iral, Anti6iral research, Antiviral, Antiviral agents, Antiviral compound, Antiviral drugs, Antiviral effect, Assay, Avian, Avian virus, Avian viruses, Cell culture, Control group, Control mice, Different doses, Dos, Embryonated chicken eggs, Enzyme activity, Exact test, Gubareva, Hayden, High doses, Hong kong, Infection, Inhibitor, Jude research hospital, Lene6a, Mdck, Mdck cells, Mendel, Mouse, Mouse brain, Mouse lungs, Mouse model, Mutant, Neuraminidase, Neuraminidase inhibitor, Neuraminidase inhibitors, Oral administration, Percent inhibition, Plaque assay, Replication, Rimantadine, Sidwell, Survival rate, Survivor, Titer, Treatment groups, Untreated mice, Viral replication, Virol, Virus, Virus infection, Virus replication, Virus titer, Virus titers, Weight loss, Zanamivir.

Abstract

Abstract: In 1997, an H5N1 avian influenza A/Hong Kong/156/97 virus transmitted directly to humans and killed six of the 18 people infected. In 1999, another avian A/Hong/1074/99 (H9N2) virus caused influenza in two children. In such cases in which vaccines are unavailable, antiviral drugs are crucial for prophylaxis and therapy. Here we demonstrate the efficacy of the neuraminidase inhibitor GS4104 (oseltamivir phosphate) against these H5N1 and H9N2 viruses. GS4071 (the active metabolite of oseltamivir) inhibited viral replication in MDCK cells (EC50 values, 7.5–12 μM) and neuraminidase activity (IC50 values, 7.0–15 nM). When orally administered at doses of 1 and 10 mg/kg per day, GS4104 prevented death of mice infected with A/Hong Kong/156/97 (H5N1), mouse-adapted A/Quail/Hong Kong/G1/97 (H9N2), or human A/Hong Kong/1074/99 (H9N2) viruses and reduced virus titers in the lungs and prevented the spread of virus to the brain of mice infected with A/Hong Kong/156/97 (H5N1) and mouse-adapted A/Quail/Hong Kong/G1/97 (H9N2) viruses. When therapy was delayed until 36 h after exposure to the H5N1 virus, GS4104 was still effective and significantly increased the number of survivors as compared with control. Oral administration of GS4104 (0.1 mg/kg per day) in combination with rimantadine (1 mg/kg per day) reduced the number of deaths of mice infected with 100 MLD50 of H9N2 virus and prevented the deaths of mice infected with 5 MLD50 of virus. Thus, GS4104 is efficacious in treating infections caused by H5N1 and H9N2 influenza viruses in mice.

Url:

https://api.istex.fr/ark:/67375/6H6-9TJZPDPF-N/fulltext.pdf

DOI: 10.1016/S0166-3542(00)00123-6

Affiliations:

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Le document en format XML

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<front><div type="abstract" xml:lang="en">Abstract: In 1997, an H5N1 avian influenza A/Hong Kong/156/97 virus transmitted directly to humans and killed six of the 18 people infected. In 1999, another avian A/Hong/1074/99 (H9N2) virus caused influenza in two children. In such cases in which vaccines are unavailable, antiviral drugs are crucial for prophylaxis and therapy. Here we demonstrate the efficacy of the neuraminidase inhibitor GS4104 (oseltamivir phosphate) against these H5N1 and H9N2 viruses. GS4071 (the active metabolite of oseltamivir) inhibited viral replication in MDCK cells (EC50 values, 7.5–12 μM) and neuraminidase activity (IC50 values, 7.0–15 nM). When orally administered at doses of 1 and 10 mg/kg per day, GS4104 prevented death of mice infected with A/Hong Kong/156/97 (H5N1), mouse-adapted A/Quail/Hong Kong/G1/97 (H9N2), or human A/Hong Kong/1074/99 (H9N2) viruses and reduced virus titers in the lungs and prevented the spread of virus to the brain of mice infected with A/Hong Kong/156/97 (H5N1) and mouse-adapted A/Quail/Hong Kong/G1/97 (H9N2) viruses. When therapy was delayed until 36 h after exposure to the H5N1 virus, GS4104 was still effective and significantly increased the number of survivors as compared with control. Oral administration of GS4104 (0.1 mg/kg per day) in combination with rimantadine (1 mg/kg per day) reduced the number of deaths of mice infected with 100 MLD50 of H9N2 virus and prevented the deaths of mice infected with 5 MLD50 of virus. Thus, GS4104 is efficacious in treating infections caused by H5N1 and H9N2 influenza viruses in mice.</div>
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The neuraminidase inhibitor GS4104 (oseltamivir phosphate) is efficacious against A/Hong Kong/156/97 (H5N1) and A/Hong Kong/1074/99 (H9N2) influenza viruses

The neuraminidase inhibitor GS4104 (oseltamivir phosphate) is efficacious against A/Hong Kong/156/97 (H5N1) and A/Hong Kong/1074/99 (H9N2) influenza viruses

Source :

English descriptors

Abstract

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