An antiviral principle present in a purified fraction from Melia azedarach L. leaf aqueous extract restrains herpes simplex virus type 1 propagation

Abstract

Meliacine (MA), an antiviral principle isolated from leaves of Melia azedarach L., exhibits potent antiviral activity against herpes simplex virus type 1 (HSV-1) by inhibiting specific infected-cell polypeptides (ICPs) produced late in infection. Some of these are involved in DNA synthesis and in the assembly of nucleocapsids. The present report provides additional evidence to elucidate the mode of action of MA against HSV-1. Time-of-addition experiments confirmed that MA affects a late event in the multiplication cycle of HSV-1. We showed that MA diminished the synthesis of viral DNA and inhibited the spread of infectious viral particles when HSV-1 that expresses beta-galactosidase activity was used. In addition, the lack of a protein with an apparent MW of 55 KD was detected in MA-treated cell extracts. Ultrastructural analysis of infected cells showed that, in the case of MA treatment, a large number of unenveloped nucleocapsids accumulated in the cytoplasm and a minor proportion of mature virus was found in cytoplasmic vesicles.These findings suggest that MA exerts an antiviral action on both the synthesis of viral DNA and the maturation and egress of HSV-1 during the infection of Vero cells.

Antiviral activities of extracts from Hong Kong seaweeds

“…Until now, chemically synthesized or modified compounds have been the major source of selective antiviral agents, particularly in the case of antiherpetic compounds (Alché et al, 2002). For combating drug resistant viral strain, it has been suggested that the new antiherpes drugs should be non-nucleosides.…”

“…Approximately 80% of the adult population worldwide are infected with herpes simplex virus (HSV) type 1 (HSV-1) and approximately 20% of them are also infected with HSV type 2 (HSV-2) (Chutkowski et al, 2002). Until now, a number of nucleoside analogues, especially the guanosine analogue acyclovir, have been developed as antiherpetic agents (Alché et al, 2002). The therapeutic limitation of these nucleoside analogues is that drug resistant strains develop readily through mutations in viral genes for thymidine kinase and/or polymerase.…”

Herpes simplex virus: Drug resistance and new treatment options using natural products (Review)

“…Time-of-addition experiments have shown that meliacine acts in the late stages of the HSV-1 replication cycle. Specific infected-cell polypeptides, some of which play a part in DNA synthesis and in the assembly of nucleocapsids, were inhibited by the addition of meliacine (43). The same group also exhibited meliacine activity in vivo in a model of herpetic stromal keratitis in mice.…”

Therapeutic effect of meliacine, an antiviral derived from Melia azedarach L., in mice genital herpetic infection

“…Interestingly, MA strongly inhibited the replication of HSV-1 in Vero cells (Villamil et al, 1995) and exhibited a synergistic antiviral activity when combined with acyclovir (Barquero and Villamil, 1997). Electron microscopic studies performed by Alché et al (2002) on infected Vero cells incubated in the presence of meliacine suggested that MA exerts its antiviral action on both the synthesis of viral DNA and the maturation and progress of HSV-1 particles.…”