Oseltamivir acid (GS4071) is a potent influenza virus neuraminidase inhibitor and the prodrug of GS4071.

Neuraminidase:100 nM.

Oseltamivir acid 是一种高效的流感病毒神经氨酸酶抑制剂，在Madin Darby犬肾 (MDCK) 细胞中对A/NWS/33 (H1N1)、A/Victoria/3/75 (H3N2)、A/Shangdong/09/93 (H3N2) 和B/Hong Kong/5/72 病毒有强烈的抑制作用。这些实验中50%有效浓度范围为1.8至59.5 microM，且在1000 microM浓度下未见明显的细胞毒性 [1]。流感B型和A/H1N1病毒对奥司他韦敏感（平均B型IC50值：13 nM；平均H1N1 IC50值：1.34 nM）。A/H1N2和A/H3N2病毒对奥司他韦更敏感（平均H3N2 IC50值：0.67 nM；平均H1N2 IC50值：0.9 nM）[2]。

GS4104，Oseltamivir acid的乙酯前药，通过口腔灌胃(p.o.)给药，在由这些病毒引起的小鼠感染中显示出显著的抑制效果。在高达100 mg/kg/天的剂量下未见毒性。GS4104的最小有效剂量为0.1 mg/kg/天，此化合物需每日两次给药，连续5天，从暴露病毒前4小时开始给药。即使在小鼠暴露于流感A (H1N1)病毒后48至至少60小时开始口服GS4104治疗，仍能显著产生抗病毒效果，延迟时间取决于病毒挑战剂量 [1]。Oseltamivir对VN1203/04的体内抗病毒效果呈剂量依赖性。5天给药方案，以每天10 mg/kg的剂量保护了50%的小鼠；此治疗组中的死亡延迟，表明治疗完成后残留病毒的复制。8天给药方案提高了oseltamivir的效果，1和10 mg/kg/天的剂量显著降低了器官中的病毒滴度，并分别提供了60%和80%的生存率 [3]。

Female 6-week-old BALB/c mice were anesthetized with isofluorane and intranasally inoculated with 50 μL of 10-fold serial dilutions of VN1203/04 virus in PBS. The mouse lethal dose (MLD50) was calculated after a 16-day observation period. Oseltamivir was administered by oral gavage twice daily for 5 or 8 days to groups of 10 mice at dosages of 0.1, 1, and 10 mg/kg/day. Control (infected but untreated) mice received sterile PBS on the same schedule. Four hours after the first dose of oseltamivir, the mice were inoculated intranasally with 5 MLD50 of VN1203/04 virus in 50 μL of PBS. Survival and weight change were observed for 24 days. Virus titers in the mouse organs were determined on days 3, 6, and 9 after inoculation. Three mice from each experimental and placebo group were killed, and the lungs and brains were removed. The organs were homogenized and suspended in 1 mL of PBS. The cellular debris was cleared by centrifugation at 2000 g for 5 min. The limit of virus detection was 0.75 log10 EID50. For calculation of the mean, samples with a virus titer <0.75 log10 EID50/mL were assigned a value of 0. Virus titers in each organ were calculated by use of the method of Reed and Muench and are expressed as mean log10 EID50/mL ± SE [3].