PLoS One ：攻击“变异甲流”的新药

　　

生物通报道，NexBi.Inc,美国疾病控制和预防中心（CDC）流感中心，香港大学病理与微生物系的科学家在最近的PLoS One上发表研究论文Novel Pandemic Influenza A(H1N1) Viruses Are Potently Inhibited by DAS181, a Sialidase Fusion Protein，称找到一种对甲流病毒有效的新药，据悉，该药对耐达菲的毒株也有效。

 

甲流疫情横扫全球，据报道，目前约有50多例甲流病毒对达菲耐药的现象出现，尽管，达菲和乐感清是目前抵制甲流的有效药物，从战略的高度上看，尽快开发新一代的抗甲流药物具有十分重要的意义。

 

据文章介绍，新药是一种唾液酸酶融合蛋白（sialidase fusion Protein），名为DAS181（FludaseTM）。

 

DAS181主要通过抑制甲流病毒复制来发挥作用。与达菲等神经氨酸酶抑制剂类药物不同，DAS181的主要成分是唾液酸酶融合蛋白。它作用的对象是细胞本身，使宿主细胞表面的唾液酸受体失去活性，流感病毒就无法与受体结合，也就无法附着细胞。而达菲等药物的原理是抑制流感病毒表面的神经氨酸酶，使其无法感染细胞，因此病毒容易发生变异产生耐药性。

由于DAS181不直接作用于病毒，不容易出现病毒耐药性问题。

 

DAS181在鼠、MDCK细胞、分化的人类上呼吸道组织以及支气管组织上的试验取得了良好的疗效。

 

研究发现DAS181对新甲流H1N1以及普通季节性流感和耐达菲毒株H274Y都有效。

 

流感病毒最大的特点就是易变，在传播过程中容易变得对抗病毒药物产生耐药性。目前甲型H1N1流感病毒在世界多个国家传播，临床中通常使用瑞士罗氏公司的达菲进行治疗。但据报道，全球已报告50多例对达菲产生耐药性的甲型H1N1流感病例。

（生物通 小茜）

生物通推荐原文摘要

Novel Pandemic Influenza A(H1N1) Viruses Are Potently Inhibited by DAS181, a Sialidase Fusion Protein

Background

The recent emergence of a novel pandemic influenza A(H1N1) strain in humans exemplifies the rapid and unpredictable nature of influenza virus evolution and the need for effective therapeutics and vaccines to control such outbreaks. However, resistance to antivirals can be a formidable problem as evidenced by the currently widespread oseltamivir- and adamantane-resistant seasonal influenza A viruses (IFV). Additional antiviral approaches with novel mechanisms of action are needed to combat novel and resistant influenza strains. DAS181 (Fludase™) is a sialidase fusion protein in early clinical development with in vitro and in vivo preclinical activity against a variety of seasonal influenza strains and highly pathogenic avian influenza strains (A/H5N1). Here, we use in vitro, ex vivo, and in vivo models to evaluate the activity of DAS181 against several pandemic influenza A(H1N1) viruses.

 

Methods and Findings

The activity of DAS181 against several pandemic influenza A(H1N1) virus isolates was examined in MDCK cells, differentiated primary human respiratory tract culture, ex-vivo human bronchi tissue and mice. DAS181 efficiently inhibited viral replication in each of these models and against all tested pandemic influenza A(H1N1) strains. DAS181 treatment also protected mice from pandemic influenza A(H1N1)-induced pathogenesis. Furthermore, DAS181 antiviral activity against pandemic influenza A(H1N1) strains was comparable to that observed against seasonal influenza virus including the H274Y oseltamivir-resistant influenza virus.

 

Conclusions

The sialidase fusion protein DAS181 exhibits potent inhibitory activity against pandemic influenza A(H1N1) viruses. As inhibition was also observed with oseltamivir-resistant IFV (H274Y), DAS181 may be active against the antigenically novel pandemic influenza A(H1N1) virus should it acquire the H274Y mutation. Based on these and previous results demonstrating DAS181 broad-spectrum anti-IFV activity, DAS181 represents a potential therapeutic agent for prevention and treatment of infections by both emerging and seasonal strains of IFV.