Unsaturated monoglycerides and alcohols of chain lengths of 16 or 18 carbons were found to be extremely potent inactivators of two enveloped viruses, herpes simplex virus type 2 and bacteriophage (p6. The lipid-containing bacteriophage PM2 was also inactivated by some of these amphiphilic molecules. Treatment of herpes simplex virus type 2 with these compounds at concentrations as low as 0.2 ,M reduced virus survival to 50% in 30 min, making these agents the most potent inactivators of herpes simplex viruses discovered that are not cytotoxic to mammalian cells. Detailed characterizations of the effects of unsaturated monoglycerides and alcohols on bacteriophages (p6 and PM2 showed that the inactivated (p6 virion remained nearly intact but that PM2 was almost completely disrupted by the inactivating treatment. Some of the compounds inactivate the viruses even at low temperature (0°C). Excess amounts of diglycerides and phospholipids interfere with the inactivating abilities of some of the unsaturated monoglycerides and alcohols against (p6 and PM2. Our findings suggest that the unsaturated monoglycerides and some of the unsaturated alcohols should be further studied as potential antiviral agents, particularly for application to herpesvirus-infected areas of the skin and accessible epithelium.It was reported 30 years ago that an unsaturated fatty acid (oleic acid, 18:1, A9 cis) inactivates influenza type A virions (16). Very little work on the potential antiviral activity of low concentrations of fatty acids and other hydrocarbon derivatives has been done until recently. We recently reported that oleic acid and palmitoleic acid (16:1, A9 cis) are potent inactivators of the lipid-containing bacteriophage p6 (10) and inhibitors of the entry process of another lipidcontaining bacteriophage, PR4 (8). The common food additive BHT (butylated hydroxytoluene) has been shown to inactivate a variety of lipidcontaining viruses, including herpes simplex virus (HSV), Newcastle disease virus, bacteriophage (6, and bacteriophage PM2 (2,3,14,19). The methyl ester derivative of the polyene antibiotic amphotericin B inactivates vesicular stomatitus virus (6), and some saturated long-chain alcohols inactivate HSV, (p6, and PM2 (15).None of these agents inactivates non-lipid-containing viruses at the low concentrations that cause inactivation of the tested lipid-containing viruses.We are conducting a comprehensive survey of the antiviral effects of fatty acid derivatives. We report here that some unsaturated long-chain alcohols and monoglycerides exhibit extremely potent virucidal effects against HSV and bacteriophages (p6 and PM2. We also report the results of studies on the mechanism(s) of these effects on the two lipid-containing bacterial viruses.MATERIALS AND METHODS Viruses and cells. Bacteriophage (p6 (18) contains a loose envelope structure composed of phospholipid and protein (1, 9, 12), making it structurally similar to the enveloped animal viruses. Bacteriophage PM2 (4) contains an internal lipid bilayer whose structure an...