Emodin is a novel alkaline nuclease inhibitor that suppresses herpes simplex virus type 1 yields in cell cultures.
OBJECTIVE
Most antiviral therapies directed against herpes simplex virus (HSV) infections are limited to a small group of nucleoside analogues that target the viral polymerase. Extensive clinical use of these drugs has led to the emergence of resistant viral strains, mainly in immunocompromised patients. This highlights the need for the development of new anti-herpesviral drugs with novel targets. Herein the effects of a plant anthraquinone, emodin, on the HSV-1 alkaline nuclease activity and virus yields were investigated.


METHODS
HSV-1 alkaline nuclease activity was examined by nuclease activity assay. Inhibition of virus yields was measured by plaque reduction assay and immunohistochemical staining. Interaction between emodin and alkaline nuclease was analysed by docking technology.


RESULTS
Emodin specifically inhibited the nuclease activity of HSV-1 UL12 alkaline nuclease in a biochemical assay. Plaque reduction assay revealed that emodin reduced the plaque formation with an EC(50) of 21.5+/-4.4 muM. Immunohistochemical staining using the anti-nucleocapsid protein antibody demonstrated that emodin induced the accumulation of viral nucleocapsids in the nucleus in a dose-dependent manner. Docking analysis further suggested that the inhibitory effect of emodin on the UL12 activity may result from the interaction between emodin and critical catalytic amino acid residues of UL12.


CONCLUSIONS
Our findings suggest that emodin is a potent anti-HSV agent that inhibits the yields of HSV-1 via the suppression of a novel target, UL12.
Hsiang
C-Y
CY
Department of Microbiology, China Medical University, Taichung, Taiwan.
Ho
T-Y
TY
D000818:Animals; D002213:Capsid / Q000737:chemistry; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004642:Emodin / Q000494:pharmacology*; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000502:physiology; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D012260:Ribonucleases / Q000037:antagonists & inhibitors*; D014709:Vero Cells / Q000821:virology*; D014779:Virus Replication / Q000187:drug effects* / Q000502:physiology
D011994:Recombinant Proteins; D012260:Ribonucleases; C066964:viral alkaline nuclease; D004642:Emodin