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

Yuan, S

For AIV infection cure, suppression of viral replication or assembly has been adopted at the same time as well. 48 NA inhibitors, such as Oseltamivir and Relenza (or called Zanamivir), are usually the first choice for AIV inhibition. 1, 2, 48 Besides them, the other two licensed M2 ion-channel inhibitors, amantadine and rimantadine, are also used. 49, 50 Another NA inhibitor, peramivir (BioCryst Pharmaceuticals, Durham, NC, USA), was in phase 3 trials in 2009 for both intravenous and intramuscular routes of administration. 51 Another long-acting NA inhibitor, designated CS-8958, was under study for use by inhalation, in Japan. 52 The viral polymerase inhibitor T-705 (Favipiravir) was not only active against all three types of influenza virus (A, B and C) but also had some activity against other RNA viruses, including some of the hemorrhagic fever viruses. 53, 54 Sialidase fusion protein inhibitor DAS181 (Fludase) is a fusion construct that incorporates the sialidase from Actinomyces viscosus, a common oral bacterium linked to a human-epitheliumanchoring domain; it can be mass produced in Escherichia coli. 55 The sialidase targets the viral attachment process, an early event in the replication of the influenza virus. 55,56 Viral hemagglutinin inhibitors cyanovirin-N and thiazolides were also tested for H1N1 infection. 57, 58 Some new anti-influenza drugs have been developed recently, such as mechanism-based covalent NA inhibitors 59 and Geldanamycin (an inhibitor of the viral polymerase assembly chaperone Hsp90). 60, 61 Moreover, combination therapy with currently available antivirals was supported by data from animal models and some clinical studies. The combinations may reduce the risk of development of resistant influenza virus strains. 62, 63 To alleviate ARDS, mechanical ventilation, high-flow oxygen therapy, inhaled nitric oxide administration, corticosteroid injection (although short-term high-dose glucocorticoids may cause necrosis of the femoral head) 64 and other conventional approaches are also usually applied for critical patients. 23, 24, 48, 65, 66 The various strategies used for ARDS care have been extensively reviewed elsewhere. 65, 66 Conclusions and Perspective Clinical Trial AIV mutates vary rapidly and new viruses emerge constantly (H7N9 was possibly made from a combination of avian influenza A H9N2 and some other AIVs). 2,10 Antiviral resistance mutations in specimens from patients with H7N9 infection have been reported recently. 67 Thus, vaccine development will always be one step behind. Therefore, we should pay more attention to the responses of the human body rather than to the characters of the virus itself. If the excessive inflammatory response is restrained, AIV may be cleared later by the body's immune mechanism, as is the case of ordinary influenza.