Morokutti-Kurz Martina, König-Schuster Marielle, Koller Christiane, Graf Christine, Graf Philipp, Kirchoff Norman, Reutterer Benjamin, Seifert Jan-Marcus, Unger Hermann, Grassauer Andreas, Prieschl-Grassauer Eva, Nakowitsch Sabine
Marinomed Biotechnologie GmbH, Vienna, Austria.
Laboratory of Tropical Veterinary Medicine, Veterinary University Vienna, Vienna, Austria.
PLoS One. 2015 Jun 8;10(6):e0128794. doi: 10.1371/journal.pone.0128794. eCollection 2015.
Carrageenan is a clinically proven and marketed compound for the treatment of viral upper respiratory tract infections. As infections caused by influenza virus are often accompanied by infections with other respiratory viruses the combination of a specific anti-influenza compound with the broadly active antiviral polymer has huge potential for the treatment of respiratory infections. Thus, the combination of the specific anti-influenza drug Zanamivir together with carrageenan in a formulation suitable for intranasal application was evaluated in-vitro and in-vivo.
We show in-vitro that carrageenan and Zanamivir act synergistically against several influenza A virus strains (H1N1(09)pdm, H3N2, H5N1, H7N7). Moreover, we demonstrate in a lethal influenza model with a low pathogenic H7N7 virus (HA closely related to the avian influenza A(H7N9) virus) and a H1N1(09)pdm influenza virus in C57BL/6 mice that the combined use of both compounds significantly increases survival of infected animals in comparison with both mono-therapies or placebo. Remarkably, this benefit is maintained even when the treatment starts up to 72 hours post infection.
A nasal spray containing carrageenan and Zanamivir should therefore be tested for prevention and treatment of uncomplicated influenza in clinical trials.
角叉菜胶是一种经临床验证并已上市的用于治疗病毒性上呼吸道感染的化合物。由于流感病毒引起的感染常伴有其他呼吸道病毒感染,将一种特定的抗流感化合物与具有广泛活性的抗病毒聚合物联合使用在治疗呼吸道感染方面具有巨大潜力。因此,对适合鼻内应用的制剂中特定抗流感药物扎那米韦与角叉菜胶的组合进行了体外和体内评估。
我们在体外表明,角叉菜胶和扎那米韦对几种甲型流感病毒株(H1N1(09)pdm、H3N2、H5N1、H7N7)具有协同作用。此外,我们在C57BL/6小鼠中用低致病性H7N7病毒(HA与甲型禽流感A(H7N9)病毒密切相关)和H1N1(09)pdm流感病毒建立的致死性流感模型中证明,与单一疗法或安慰剂相比,两种化合物联合使用可显著提高感染动物的存活率。值得注意的是,即使在感染后72小时开始治疗,这种益处仍然存在。
因此,应在临床试验中测试含有角叉菜胶和扎那米韦的鼻喷雾剂对单纯性流感的预防和治疗效果。