Enhancement of non-specific resistance to viral infection by muramyldipeptide and its analogs.

Antiviral activity of muramyldipeptide (MDP) and its lipophilic derivatives, B30-MDP and MDP-Lys(L18), was investigated in mice infected with vaccinia virus (VV) and herpes simplex virus type 2 (HSV-2). Mice administered these compounds subcutaneously or orally were protected against VV in tail lesion tests and against HSV-2 in skin lesion tests, respectively. Since in vitro antiviral activity was not demonstrated with these compounds in cultured mammalian cells infected with either VV or HSV-2, host-mediated defense mechanisms may play a role in the activity of the compounds. As for serum interferon (IFN) induction, MDP and its analogs showed no activity in mice, suggesting that IFN does not participate in the antiviral mechanisms against VV and HSV-2. An extrinsic antiviral activity was demonstrated when peritoneal macrophages from the mice administered these compounds were cocultivated with VV-infected 3T3 cells. The results indicate that macrophage activation by MDP and its analogs plays a role in the defense mechanisms against viral infection. This activity was not virus-specific. We also demonstrate that the introduction of lipophilic residue(s) into MDP enhances the antiviral activity of mice against VV and HSV-2.