Broad-spectrum antiviral activity of chebulagic acid and punicalagin against viruses that use glycosaminoglycans for entry

Abstract

BackgroundWe 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.ResultsExtensive 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.ConclusionsCHLA 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.

A Small Molecule Inhibits Virion Attachment to Heparan Sulfate- or Sialic Acid-Containing Glycans

“…Molecules that interfere with these low-affinity interactions often have antiviral activities. Such compounds act as receptor mimetics, competing for virion binding to cellular heparan sulfate or sialic acid moieties (21)(22)(23)(24)(25). However, such inhibitors are restricted to the viruses that bind to either heparan sulfate or sialic acid.…”

Antiviral Activity of Herbal Extracts Against the Tick Borne Encephalitis Virus (Literature Review)

“…Более того, в предварительных экспериментах у экстракта T. chebula также обнаружена нейтра-лизующая активность в отношении вируса КЭ [8]. Можно предположить, что способность этого экстракта нейтрализовать вирус КЭ обусловлена присутствием хебулиевой кислоты и пуникалагина, ингибирующих близкородственный флавивирус -вирус Денге [20]. Однако на данном этапе исключить альтернативные действующие противовирусные агенты исследований невозможно.…”

“…Недавно L.T. Lin et al (2013) было показано, что два компонента T. chebula -хебулиевая кислота и пуникалагин -обладают широким спектром анти-вирусной активности, в том числе и против вируса Денге [20]. Эти два вещества инактивировали сво-бодные частицы вируса Денге, что в конечном итоге влияло на процессы прикрепления и слияния вируса с клеткой в ранние стадии проникновения вируса в клетку.…”

Strategies to Preclude Hepatitis C Virus Entry

“…SSb2 could inactivate cell-free HCV particles and was suggested to target the glycoprotein E2 in mediating its antiviral effect against HCV infection. Several other natural compounds including the gallic acid (GA) extracted from Limonium sinense [103], the hydrolyzable tannins chebulagic acid (CHLA) and punicalagin (PUG) [104], and the hepatoprotective plant Phyllanthus urinariaderived monolactone loliolide (LOD) [105] and butenolide (4R,6S)-2-dihydromenisdaurilide (DHMD) [106] were also found to efficiently inactivate cell-free HCV viral particles and impede viral attachment. Another natural compound curcumin extracted from turmeric was shown to decrease the fluidity of viral envelope and therefore prevent the binding and fusion [107], possibly by inserting into the membrane in a manner similar to cholesterol [108].…”

“…Several molecules also block cell-to-cell spread in addition to their activities in hindering HCV viral entry. For instance, besides impeding viral attachment, CHLA and PUG exhibit pronounced antiviral effects at the postinfection stage, especially in restricting HCV foci expansion [104]. Others include EGCG [99], curcumin [107], erlotinib, and dasatinib [54].…”