Antiviral activity of 2-hydroxy fatty acids

Abstract

Following an earlier demonstration of an antiviral effect against varicella-zoster virus (VZV, human herpesvirus 3) using 2-hydroxymyristic acid (2-hydroxytetradecanoic acid; 2-HM), an inhibitor of protein myristoylation, both 2-HM and 2-hydroxypalmitic acid (2-hydroxyhexadecanoic acid; 2-HP) have been tested against a range of viruses. Although both compounds inhibit the replication of varicella-zoster virus (VZV; human herpesvirus 3) they do not inhibit the replication of closely related herpesviruses. They do, however, inhibit the replication of both poliovirus (a member of the Picornaviridae) and the human immunodeficiency virus type 1 (HIV-1; a member of the Retroviridae). Neither compound is toxic to adherent cells by dye uptake assay, although limited toxicity is apparent to non-adherent cell lines at high concentrations. The mechanisms underlying these effects are discussed. A diminished effect of 2-hydroxymyristic acid when the compound is dissolved in dimethyl sulphoxide (DMSO) rather than ethanol is reported, and the implications for the use of DMSO as a 'universal solvent' for compound screening noted. Finally, it is suggested that targeting of 'virus-essential' cellular functions may provide an alternative route for inhibiting viral replication.