The anti-herpes simplex virus activity of n-docosanol includes inhibition of the viral entry process

• Published in: Antiviral research 1998-12, Vol.40 (1), p.85-94
• Main Authors: Pope, Laura E, Marcelletti, John F, Katz, Lee R, Lin, Janet Y, Katz, David H, Parish, Mary Lynn, Spear, Patricia G
• Format: Article
• Language: English
• Subjects: Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral activity; Antiviral agents; Antiviral Agents - pharmacology; B-Lymphocytes - metabolism; B-Lymphocytes - virology; beta-Galactosidase - biosynthesis; Biological and medical sciences; Cell Line; Cell Membrane - drug effects; Cercopithecus aethiops; CHO Cells; Cricetinae; Entry; Fatty alcohol; Fatty Alcohols - pharmacology; Fluorescent Dyes; Herpes simplex virus; Herpesvirus 1, Human - drug effects; Herpesvirus 1, Human - metabolism; Herpesvirus 1, Human - physiology; Herpesvirus 2, Human - drug effects; Herpesvirus 2, Human - metabolism; Herpesvirus 2, Human - physiology; Humans; lacZ gene; Mechanism of action; Medical sciences; Membrane Fusion; n-Docosanol; Pharmacology. Drug treatments; Receptors, Virus - metabolism; Rhodamines; Tumor Cells, Cultured; Vero Cells
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/S0166-3542(98)00048-5

n-Docosanol-treated cells resist infection by a variety of lipid-enveloped viruses including the herpesviruses. Previous studies of the mechanism of action demonstrated that n-docosanol inhibits an event prior to the expression of intermediate early gene products but subsequent to HSV attachment. The studies reported here indicate that n-docosanol inhibits fusion of the HSV envelope with the plasma membrane. Evidence suggests that antiviral activity requires a time-dependent metabolic conversion of the compound. Cellular resistance to infection declines after removal of the drug with a t 1/2 of approximately 3 h. Reduced expression of viral genes in n-docosanol-treated cells was confirmed by a 70% reduction in expression of a reporter gene regulated by a constitutive promoter inserted into the viral genome. Inhibited release in treated cells of virion-associated regulatory proteins—an immediate post entry event—was indicated by a 75% reduction in the expression of β-galactosidase in target cells carrying a stably transfected lacZ gene under control of an HSV immediate—early promoter. Finally, the fusion-dependent dequenching of a lipophilic fluorescent probe, octadecyl rhodamine B chloride, inserted into the HSV envelope was significantly inhibited in treated cells. Inhibition of fusion between the plasma membrane and the HSV envelope, and the subsequent lack of replicative events, may be the predominant mechanism for the anti-HSV activity of n-docosanol.