Inhibition of herpes simplex virus infection by tannins and related compounds

Fukuchi, Kunihiko; Sakagami, Hiroshi; Okuda, Takuo; Hatano, Tsutomu; Tanuma, Sei Ichi; Kitajima, Ken; Inoue, Yasuo; Inoue, Sadako; Ichikawa, Shinya; Nonoyama, Meihan; Konno, Kunio

doi:10.1016/0166-3542(89)90038-7

Cited by 165 publications

(93 citation statements)

References 19 publications

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“…These include 1,3,4,6-tetra-O-galloyl-␤-D-glucose (77), casuarinin (10), ent-epiafzelechin-(4␣3R8)-epiafzelechin (17), excoecarianin (16), geraniin (77), hippomanin A (76), prodelphinidin B-2 3Ј-O-gallate (11), prodelphinidin B-2 3,3Ј-di-O-gallate (12), pterocarnin A (13), and putranjivain A (14). Studies from other laboratories have also reported a series of tannins and related compounds capable of inhibiting HSV infections (25,56,64,71,72). These earlier reports provide strong precedent for our studies and suggest that the tannins constitute an excellent focus for antiviral discovery, particularly in the field of HSV therapeutics.…”

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confidence: 99%

Hydrolyzable Tannins (Chebulagic Acid and Punicalagin) Target Viral Glycoprotein-Glycosaminoglycan Interactions To Inhibit Herpes Simplex Virus 1 Entry and Cell-to-Cell Spread

Lin

Chen

Chung

et al. 2011

J Virol

163

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Herpes simplex virus 1 (HSV-1) is a common human pathogen that causes lifelong latent infection of sensory neurons. Non-nucleoside inhibitors that can limit HSV-1 recurrence are particularly useful in treating immunocompromised individuals or cases of emerging acyclovir-resistant strains of herpesvirus. We report that chebulagic acid (CHLA) and punicalagin (PUG), two hydrolyzable tannins isolated from the dried fruits of Terminalia chebula Retz. (Combretaceae), inhibit HSV-1 entry at noncytotoxic doses in A549 human lung cells. Experiments revealed that both tannins targeted and inactivated HSV-1 viral particles and could prevent binding, penetration, and cell-to-cell spread, as well as secondary infection. The antiviral effect from either of the tannins was not associated with induction of type I interferon-mediated responses, nor was pretreatment of the host cell protective against HSV-1. Their inhibitory activities targeted HSV-1 glycoproteins since both natural compounds were able to block polykaryocyte formation mediated by expression of recombinant viral glycoproteins involved in attachment and membrane fusion. Our results indicated that CHLA and PUG blocked interactions between cell surface glycosaminoglycans and HSV-1 glycoproteins. Furthermore, the antiviral activities from the two tannins were significantly diminished in mutant cell lines unable to produce heparan sulfate and chondroitin sulfate and could be rescued upon reconstitution of heparan sulfate biosynthesis. We suggest that the hydrolyzable tannins CHLA and PUG may be useful as competitors for glycosaminoglycans in the management of HSV-1 infections and that they may help reduce the risk for development of viral drug resistance during therapy with nucleoside analogues.Herpes simplex virus 1 (HSV-1) is an alphaherpesvirus that typically causes mucocutaneous lesions in oral, perioral, and other mucosal sites in the body (58). The virus commonly uses the oropharyngeal mucosa as a port of entry, and after primary infection, establishes a lifelong latent state in the host's trigeminal ganglia sensory neurons. Sporadic recurring infections occur when HSV-1 is reactivated by various stimuli, such as sunlight, immunosuppression, menstruation, fever, or stress (23). Although primary or reactivated HSV-1 infections can be subclinical or manifested by mild and self-limited diseases, severe cases of this viral infection may lead to complications such as keratoconjunctivitis, meningitis, and encephalitis (3, 5). Importantly, corneal HSV-1 infection can lead to stromal keratitis, which remains one of the leading causes of blindness in developing countries (37). More aggressive diseases due to HSV-1 are common in immunocompromised individuals (3,5,23). To date, no treatment has been identified that eradicates or resolves latent infections by this ubiquitous pathogen.HSV-1 viral entry into cells is initiated by interaction of viral envelope glycoproteins (gB and gC) with host cell surface proteoglycans (PGs) conjugated to glycosaminoglycans (GAGs) containing...

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Hydrolyzable Tannins (Chebulagic Acid and Punicalagin) Target Viral Glycoprotein-Glycosaminoglycan Interactions To Inhibit Herpes Simplex Virus 1 Entry and Cell-to-Cell Spread

Lin

Chen

Chung

et al. 2011

J Virol

163

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“…LCC exhibited high affinity with influenza virus, and in contact to LCC, influenza virus rapidly lose the virulence . LCC showed much higher anti-HIV activity than tannins (Nakashima, et al, 1992a(Nakashima, et al, , 1992b, whereas both LCC and tannins showed potent anti-HSV activity (Fukuchi, et al, 1989a(Fukuchi, et al, , 1989b. Since virus is one of major risk factor of oral cavity cancer (Sakagami, 2010a), anti-viral action of LCC may reduce the incidence of virus-triggered diseases such as cancer.…”

Section: Resultsmentioning

confidence: 99%

Treatment of Herpes Simplex Virus with Lignin-Carbohydrate Complex Tablet, an Alternative Therapeutic Formula

López¹,

Yamamoto²,

Sakagami³

2012

Antiviral Drugs - Aspects of Clinical Use and Recent Advances

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“…21) Tannin-containing compounds have been reported to exert various biological activities such as antibacterial 22) and antiviral eŠects. [23][24][25] Ohtsu 26) reported that the mitogenic substance in Bupleurum chinence is a polyphenol. Tannin is attached to the polyphenol group as indicated by its structure with the``hydroxyl group''.…”

Section: Discussionmentioning

confidence: 99%