Drugs to cure avian influenza infection – multiple ways to prevent cell death

Yuan, S

In this review, five categories of drugs and therapeutic strategies for AIV infection have been summarized: (i) antioxidant (high-dose VC); (ii) mitochondrial permeability protectant and immunomodulators (CsA, with or without Celecoxib/Mesalazine or Eritoran); (iii) protease inhibitors (Ulinastatin); (iv) antiviral drugs (Oseltamivir/Relenza); and (v) clinical management of ARDS. Among them, licensed drugs are listed in Table 1 . High doses of VC have been used for influenza treatments for a very long time; [13] [14] [15] [16] [17] CsA has also been used to treat non-organ-transplantation-associated pneumonia; 68 Celecoxib and Mesalazine (two prescription drugs) successfully cured mice infected with H5N1; 26 and Ulinastatin has a good curative effect on acute lung injury. 45 Considering that they work on different cell death pathways, all four categories of drugs might ideally be used in a large combination to reduce the mortality rate. This therapeutic combination could be named 'avian influenza cocktail therapy' (AICT), similar to the cocktail therapy for HIV. 69 However, AICT may have additive or possible antagonistic effects on virus replication or induction of a cytokine storm. Moreover, the possible side effects of this new combination therapy have not been tested yet, although the treatment session should not be very long (usually 2-4 weeks). Moreover, the dosage of the single compound should be adjusted according to the combination. For example, the blood concentration of CsA varies largely among individual patients and may be dramatically influenced by some other drugs. [70] [71] [72] Therefore, careful pharmaceutical studies should be conducted before the AICT is made to really enter the clinical trial for human AIV infection.