Belser Jessica A, Lu Xiuhua, Szretter Kristy J, Jin Xiaoping, Aschenbrenner Laura M, Lee Alice, Hawley Stephen, Kim Do Hyong, Malakhov Michael P, Yu Mang, Fang Fang, Katz Jacqueline M
Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
J Infect Dis. 2007 Nov 15;196(10):1493-9. doi: 10.1086/522609. Epub 2007 Oct 31.
Increasing resistance to currently available influenza antivirals highlights the need to develop alternate approaches for the prevention and/or treatment of influenza. DAS181 (Fludase), a novel sialidase fusion protein that enzymatically removes sialic acids on respiratory epithelium, exhibits potent antiviral activity against influenza A and B viruses. Here, we use a mouse model to evaluate the efficacy of DAS181 treatment against a highly pathogenic avian influenza H5N1 virus. When used to treat mice daily beginning 1 day before infection with A/Vietnam/1203/2004(H5N1) virus, DAS181 treatment at 1 mg/kg/day protected 100% of mice from fatal disease, prevented viral dissemination to the brain, and effectively blocked infection in 70% of mice. DAS181 at 1 mg/kg/day was also effective therapeutically, conferring enhanced survival of H5N1 virus-challenged mice when treatment was begun 72 h after infection. This notable antiviral activity underscores the potential utility of DAS181 as a new class of drug that is effective against influenza viruses with pandemic potential.
目前可用的流感抗病毒药物耐药性不断增加，这凸显了开发预防和/或治疗流感的替代方法的必要性。DAS181（Fludase）是一种新型唾液酸酶融合蛋白，可通过酶促作用去除呼吸道上皮细胞上的唾液酸，对甲型和乙型流感病毒具有强大的抗病毒活性。在此，我们使用小鼠模型评估DAS181治疗高致病性禽流感H5N1病毒的疗效。从感染A/越南/1203/2004（H5N1）病毒前1天开始每天用于治疗小鼠时，1mg/kg/天的DAS181治疗可保护100%的小鼠免于致命疾病，防止病毒传播至大脑，并有效阻止70%的小鼠感染。当在感染后72小时开始治疗时，1mg/kg/天的DAS181在治疗方面也有效，可提高受H5N1病毒攻击的小鼠的存活率。这种显著的抗病毒活性突出了DAS181作为一类对具有大流行潜力的流感病毒有效的新型药物的潜在效用。
