Anti-hepatitis B virus activity of N-acetyl-l-cysteine (NAC): new aspects of a well-established drug

N-acetyl-l-cysteine (NAC) is commonly administered as an antidote against acetaminophen intoxication and is the preferred agent in the treatment of pulmonary diseases. It is furthermore commonly considered that it restrains human immunodeficiency virus (HIV) replication by scavenging reactive oxygen intermediates (ROI) and thus suppressing activation of nuclear factor κB (NFκB). We show here that NAC is in addition able to inhibit hepatitis B virus (HBV) replication, but by a mechanism independent of the intracellular level of reactive oxygen intermediates. Treatment of HBV-producing cell lines with NAC resulted in an at least 50-fold reduction of viral DNA in the tissue culture supernatant within 48 h. This decrease of viral DNA and thus of virions in the tissue culture supernatant is caused by a disturbance of the virus assembly, rather than by a reduction of viral transcripts. Our data strongly suggest a potential use of this well-established, non-toxic drug for the treatment of HBV infection. Since NAC, in contrast to interferon, exerts its anti-HBV activity at a posttranscriptional level, a combination of NAC with the established interferon therapy could also be considered.