Since a 100-fold molar excess of HOCl was necessary to induce the antiviral activity, all the reactions and modifications documented at low HOCl-concentrations might not explain the mechanism by which our HOCl-modified serum albumins inhibit viral entry of HIV-1 as well as West Nile virus. However, our study supports the hypothesis that HOCl might be part of the host defense against pathogens and apart from its direct toxic activity it may have an additional indirect but important activity, the transformation of a protein into an antiviral weapon [16] . From the cell culture experiments of Chase et al. and Klebanoff et al. [11, 12] , in which activated PMN cells release MPO and HOCl was generated, HOCl was suggested as the HIV-1-killing agent. Based on our results it is conceivable that the generated HOCl reacts with bovine serum albumin, which is usually present in high concentrations in cell culture media, and therefore mBSA would be present during viral infection. As we have now demonstrated, mBSA has a strong antiviral activity and might be also responsible for the antiviral effects observed in PMN cell cultures. The biological relevance of HOCl-modification of serum albumin or other proteins might be ques-tionable since virus replication in vivo is not limited to inflammatory loci, where MPO is expressed in vivo leading to the production of HOCl. To our understanding, the discovery of HOCl-modified serum albumin as an antiviral agent opens a new field for the development of nontoxic agents which can be added to blood products or can be used as a local microbicide to prevent viral transmission. Since the neutralizing activity of HOCl-modified serum albumins was documented against West Nile virus and the HIV-1 NL4-3 mutants, irrespective to their coreceptor type, future work will show how efficient HOClmodified serum albumins can neutralize other HIV-1 and HIV-2 variants as well as other viral species.