Broad-spectrum antiviral activity of chebulagic acid and punicalagin against viruses that use glycosaminoglycans for entry.
BACKGROUND
We previously identified two hydrolyzable tannins, chebulagic acid (CHLA) and punicalagin (PUG) that blocked herpes simplex virus type 1 (HSV-1) entry and spread. These compounds inhibited viral glycoprotein interactions with cell surface glycosaminoglycans (GAGs). Based on this property, we evaluated their antiviral efficacy against several different viruses known to employ GAGs for host cell entry.


RESULTS
Extensive analysis of the tannins' mechanism of action was performed on a panel of viruses during the attachment and entry steps of infection. Virus-specific binding assays and the analysis of viral spread during treatment with these compounds were also conducted. CHLA and PUG were effective in abrogating infection by human cytomegalovirus (HCMV), hepatitis C virus (HCV), dengue virus (DENV), measles virus (MV), and respiratory syncytial virus (RSV), at μM concentrations and in dose-dependent manners without significant cytotoxicity. Moreover, the natural compounds inhibited viral attachment, penetration, and spread, to different degrees for each virus. Specifically, the tannins blocked all these steps of infection for HCMV, HCV, and MV, but had little effect on the post-fusion spread of DENV and RSV, which could suggest intriguing differences in the roles of GAG-interactions for these viruses.


CONCLUSIONS
CHLA and PUG may be of value as broad-spectrum antivirals for limiting emerging/recurring viruses known to engage host cell GAGs for entry. Further studies testing the efficacy of these tannins in vivo against certain viruses are justified.
Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Liang-Tzung
LT
Lin
Ting-Ying
TY
Chen
Song-Chow
SC
Lin
Chueh-Yao
CY
Chung
Ta-Chen
TC
Lin
Guey-Horng
GH
Wang
Robert
R
Anderson
Chun-Ching
CC
Lin
Christopher D
CD
Richardson
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005960:Glucosides / Q000494:pharmacology*; D006025:Glycosaminoglycans / Q000378:metabolism*; D006801:Humans; D047348:Hydrolyzable Tannins / Q000494:pharmacology*; D011991:Receptors, Virus / Q000378:metabolism*; D014777:Virus Diseases / Q000378:metabolism / Q000821:virology*; D053586:Virus Internalization / Q000187:drug effects*; D018406:Virus Physiological Phenomena / Q000187:drug effects; D014780:Viruses / Q000187:drug effects*
D000998:Antiviral Agents; D001578:Benzopyrans; D005960:Glucosides; D006025:Glycosaminoglycans; D047348:Hydrolyzable Tannins; D011991:Receptors, Virus; C076178:chebulagic acid; C115642:punicalagin