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 agai nst acetaminophen intoxication and is the preferred agent in the treat ment of pulmonary diseases. It is furthermore commonly considered that it restrains human immunodeficiency virus (HIV) replication by scaven ging reactive oxygen intermediates (ROI) and thus suppressing activati on of nuclear factor kappa B (NF kappa B). 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 s upernatant within 48 h. This decrease of viral DNA and thus of virions in the tissue culture supernatant is caused by a disturbance of the v irus assembly, rather than by a reduction of viral transcripts. Our da ta strongly suggest a potential use of this well-established, non-toxi c drug for the treatment of HBV infection. Since NAC, in contrast to i nterferon, exerts its anti-HBV activity at a posttranscriptional level , a combination of NAC with the established interferon therapy could a lso be considered.