The high mortality of highly pathogenic
avian influenza A (H5N1) viruses
infection in humans gives rise to considerable concern that it might someday cause another lethal pandemic. At present there is no other effective alternative besides the early and enough administration of
neuraminidase inhibitors, which may be crucial for the patient management. However, its efficacy is sometimes limited because of the late administration in some patients especially the seriously ill ones and the continual occurrence of
oseltamivir resistant A (H5N1) strains. The specific candidate
vaccine are still under development and the practical value of passive immunization is hard to be widely applied because of the scarcity of convalescent human plasma, especially in the early stage of a serious and rapidly progressing pandemic.
Statins and
fibrates, both of which are used in clinical practice, have anti-inflammatory and immunomodulatory effects and other multiple biologic activities. So we hypothesized that the two
immunomodulatory agents may exhibit synergistic effects when they were combined to
neuraminidase inhibitors to treat the A (H5N1) viruses
infections via inhibiting the production of either the early inflammatory mediators (e.g., many
cytokine/
chemokine) or the late mediator (e.g., High Mobility Group Box
Protein 1), even showing the anti-viral activities with the prevention of the development of
antiviral resistance. Therefore, the novel triple combinations may be an optimal management to confront the next lethal
influenza pandemic on its very beginning.