N-acetylcysteine lacks universal inhibitory activity against influenza A viruses

About 10 percent of the human population is affected by influenza annually and several pandemic episodes have occurred throughout recorded history [1]. This context explains why continued efforts are made to identify new therapeutic molecules. Among these, N-acetylcysteine (NAC), which is commonly used for its mucolytic activity in humans, was shown to inhibit influenza virus both in mouse models, alone or in combination, with the A/PR/8 strain [2,3], and in vitro, with H5N1 strains [4]. Recently, NAC treatment was reported to reduce symptoms of influenza-like illness in humans [5] and administration of the dose of 100 mg/kg supposedly contributed to the success of the treatment of a patient infected with the 2009 pandemic H1N1 virus [6].In order to determine whether these successful results can be extrapolated to other viral strains than A/PR/8 and H5N1 strains, the effect of NAC on the clinical course and outcome of experimental influenza was assessed in mice inoculated with a lethal dose of our murinized swine H1N1 influenza strain [7]. In spite of a significant but very partial anti-influenza effect in vitro, neither percent survival nor body weight loss were altered by NAC treatment in vivo, suggesting that NAC-susceptibility of influenza A viruses is strain-dependent.Two groups of ten 8-wk old female CD-1 mice were intranasally inoculated with 10 MLD50 of murinized A/swine/Iowa/4/1976 (H1N1) virus [7]. The first group received 100 mg/kg NAC (Sigma) daily by gavage, from day 1 to day 7 post-infection (pi), while the second received the vehicle only. Clinical status, body weight (BW) and mortality were recorded daily up to day 14 pi. Challenge studies were approved by the Belgian Council for Laboratory Animal Science, under the guidance of the Institutional Animal Care and Use Committees of the University of Liège.Near confluent Vero cells (ATCC CCL-81) were infected at a multiplicity of infection of 0.01 with a Vero cell-adapted variant of the A/swine/Iowa/4/19