Antiviral activity of lactoferrin-derived peptides

Previously we have demonstrated, that bovine lactoferrin (BLf) in apo and different metal saturated forms inhibits the early phases of viral infection of enveloped and naked viruses, including herpes simplex virus type 1 (HSV-1) and 2 (HSV-2), human immunodeficiency virus type 1 (HIV-1), SA-11 rotavirus and poliovirus type 1. Inhibition of viral multiplication takes place through an interaction of lactoferrin with host cells and/or viral particles and is poorly influenced by its metal saturation. Conversely, metal saturated BLf was shown to be effective towards steps subsequent to virus internalization, in single growth curve experiments in which the effect of the protein on newly synthesised viral particles could be excluded. Since Lf is able to bind to host cell surfaces, this activity could be due to interference of metal ions, intracellularly delivered, with viral replication or assembly. In an attempt to elucidate protein moieties of Lf involved in antiviral activity, we have tested Lf tryptic derivatives towards an enveloped virus (HSV-1) and a naked virus (SA-11 rotavirus). The pool of fragments, derived from tryptic digestion, retained antiviral activity, even to lower extent than the native protein. Some purified large fragments showed an antiviral activity similar to that exerted by the Lf digested pool.