日本东京大学医学院传染病研究中心、富山化学工业株式会的科学家近日研究了一种新型的疫苗，可防治 禽流感 与甲流重组。相关的成果文章T-705 (favipiravir) activity against lethal H5N1 influenza A viruses发表在最新的PNAS上。

    治疗H5N1的药物达菲和乐感清是通过抑制H5N1病毒的神经氨酸酶来发挥作用的，然而，最新的临床数据显示，目前已经在患者中发现存在对达菲和乐感清具有耐药性的毒株。达菲和乐感清不仅是治疗禽流感的药物也是治疗目前盛行的甲流的药物。

    因此，出现这样的情况，给禽流感和甲流H1N1的重组带来新的机遇，两种病毒可能重组为具有禽流感致病性、甲流易H1N1感染性的新病毒，那么这将给人类带来巨大的灾难。

    东京大学医学院传染病研究中心、富山化学工业株式会的科学家开发的新药，T-705（RNA聚合酶的抑制剂）目前通过临床人体试验证实对耐达菲和乐感清的甲流毒株具有治疗效果，目前在小鼠动物模型上的临床试验证实，对高致病性禽流感H5N1也有良好的治疗效果。

    “T-705”因在美国犹他州立大学开展的研究中发现对感染了高致病性H5N1型禽流感病毒的小白鼠发挥了明显的治疗效果。

    在日本国内，富山化学从2008年1月开始对季节性流感患者实施了“T-705”临床第Ⅱ期实验，初步确认了这种新结构的RNA聚合酶抑制剂对于人体也有药效。同时，通过在日本国内研究所实施的动物实验，“T-705”也被确认对于在全球各国流行的甲型H1N1流感具有治疗效果。

原始出处及摘要：

PNAS December 22, 2009, doi: 10.1073/pnas.0909603107

T-705 (favipiravir) activity against lethal H5N1 influenza A viruses

Maki Kisoa, Kazumi Takahashib, Yuko Sakai-Tagawaa, Kyoko Shinyac, Saori Sakabea, Quynh Mai Led, Makoto Ozawae,f, Yousuke Furutab and Yoshihiro Kawaokaa,c,e,f,g,1

aDivision of Virology, Department of Microbiology and Immunology
eInternational Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, 108-8639 Japan
bResearch Laboratories, Toyama Chemical Co., Ltd., Toyama, 930-8508 Japan
d National Institute of Hygiene and Epidemiology, Hanoi, Vietnam
cDepartment of Microbiology and Infectious Diseases, Kobe University, Hyogo, 650-0017 Japan
gExploratory Research for Advanced Technology Infection-Induced Host Responses Project, Japan Science and Technology Agency, Saitama, 332-0012 Japan
fInfluenza Research Institute, Department of Pathological Sciences, University of Wisconsin-Madison, WI 53706

The neuraminidase inhibitors oseltamivir and zanamivi are used to treat H5N1 influenza. However, oseltamivir-resistant H5N1 viruses have been isolated from oseltamivir-treated patients. Moreover, reassortment between H5N1 viruses and oseltamvir-resistant human H1N1 viruses currently circulating could create oseltamivir-resistant H5N1 viruses, rendering the oseltamivir stockpile obsolete. Therefore, there is a need for unique and effective antivirals to combat H5N1 influenza viruses. The investigational drug T-705 (favipiravir; 6-fluoro-3-hydroxy-2-pyrazinecarboxamide) has antiviral activity against seasonal influenza viruses and a mouse-adapted H5N1 influenza virus derived from a benign duck virus. However, its efficacy against highly pathogenic H5N1 viruses, which are substantially more virulent, remains unclear. Here, we demonstrate that T-705 effectively protects mice from lethal infection with oseltamivir-sensitive or -resistant highly pathogenic H5N1 viruses. Furthermore, our biochemical analysis suggests that T-705 ribofuranosyl triphosphate, an active form of T-705, acts like purines or purine nucleosides in human cells and does not inhibit human DNA synthesis. We conclude that T-705 shows promise as a therapeutic agent for the treatment of highly pathogenic H5N1 influenza patients.