WHO Collaborating Centre for Reference and Research on Influenza, VIDRL, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia; Department of Microbiology and Immunology, University of Melbourne, Victoria, Australia.
WHO Collaborating Centre for Reference and Research on Influenza, VIDRL, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
Antiviral Res. 2020 Apr;176:104751. doi: 10.1016/j.antiviral.2020.104751. Epub 2020 Feb 20.
Combination therapy is an alternative approach to reduce viral shedding and improve clinical outcomes following influenza virus infections. In this study we used oseltamivir (OST), a neuraminidase inhibitor and nitazoxanide (NTZ), a host directed drug, and found in vitro that the combination of these two antivirals have a synergistic relationship. Using the ferret model of (A/Perth/265/2009, (H1N1)pdm09), virus infections, we found that the combination of NTZ and OST was more effective than either NTZ or OST independently in preventing infection and reducing duration of viral shedding. However, these benefits were only seen if treatment was administered prophylactically, as opposed to therapeutically. We also found that if prophylactically treated ferrets that had detectable virus in the upper respiratory tract, no virus was detected in the lower respiratory tract. This benefit was not observed with NTZ or OST alone. The combination of NTZ and OST enhances the antiviral effect of OST, which is the standard of care in most settings.
联合治疗是一种降低流感病毒感染后病毒脱落和改善临床结果的替代方法。在这项研究中，我们使用了奥司他韦（OST），一种神经氨酸酶抑制剂和硝唑尼特（NTZ），一种宿主导向药物，并发现这两种抗病毒药物在体外具有协同关系。使用雪貂模型（A/Perth/265/2009，（H1N1)pdm09），病毒感染，我们发现 NTZ 和 OST 的联合使用比单独使用 NTZ 或 OST 更有效地预防感染和减少病毒脱落持续时间。然而，只有在预防性治疗时才能看到这些益处，而不是治疗性治疗。我们还发现，如果在上呼吸道检测到病毒的预防性治疗的雪貂，在下呼吸道则未检测到病毒。单独使用 NTZ 或 OST 则没有观察到这种益处。NTZ 和 OST 的联合使用增强了 OST 的抗病毒作用，OST 是大多数情况下的标准治疗方法。
