Trachelogenin, a novel inhibitor of hepatitis C virus entry through CD81

Abstract

Although much progress has been made in antiviral agents against hepatitis C virus (HCV) in recent years, novel HCV inhibitors with improved efficacy, optimized treatment duration and more affordable prices are still urgently needed. Here, we report the identification of a natural plant-derived lignan, trachelogenin (TGN), as a potent entry inhibitor of HCV without genotype specificity, and with low cytotoxicity. TGN was extracted and purified from Caulis trachelospermi, a traditional Chinese herb with anti-inflammatory and analgesic effects. A crucial function of TGN was the inhibition of HCV entry during a post-binding step without affecting virus replication, translation, assembly and release. TGN blocked virus infection by interfering with the normal interactions between HCV glycoprotein E2 and the host entry factor CD81, which are key processes for valid virus entry. In addition, TGN diminished HCV cell-to-cell spread and exhibited additional synergistic effects when combined with IFN or telaprevir. In conclusion, this study highlights the effect of a novel HCV entry inhibitor, TGN, which has a target that differs from those of the current antiviral agents. Therefore, TGN is a potential candidate for future cocktail therapies to treat HCV-infected patients.

Chemical Characterisation-Biological Evaluation of Greek Cultivar Cardoon Seeds (Cynara cardunculus). A By-product with Potential High Added Value

“…The lignan arctigenin has been previously isolated from the seeds of the edible artichoke [16] and has revealed anti-inflammatory [17] and cytotoxic effects [18,19], while trachelogenin was isolated for the first time in the studied species as well as in the Cynara genus and has been previously isolated from other Asteraceae plants such as Centaurea jacea [20] and the seeds of Rhaponticum carthamoides [21]. According to the literature, trachelogenin is a metabolite known for its antihypertensive action and its potential antiproliferative effects [22] against leukaemia, HIV, and hepatitis C viruses [23][24][25]. In addition, a mixture of the lignans trachelogenin and ethylate of trachelogenin was isolated, where ethylate of trachelogenin was determined for the first time from a natural source, as it has been previously referred to only through chemical synthesis [26].…”

Design of Inhibitory Peptides of the Interaction between the E2 Protein of the Hepatitis C Virus and the CD81 and CD209 receptors

“…Finally, a considerable amount of studies on non peptidic molecules have aimed to inhibit the function or interaction of the E2-HCV protein to diminish the replication percentage of HCV [43][44][45][46][47][48][49][50][51][52] . Unlike these molecules, the structural and physicochemical characteristics of the peptides make them more effective candidates for inhibition of protein interactions because they can bind through hot-spot sites from the interaction among proteins, thus, blocking the canonical interaction of the target proteins.…”

Phytochemistry, Pharmacology and Traditional Uses of Plants from the Genus Trachelospermum L.

“…As for the effective ingredient, compound 9 isolated from T. jasminoides was recognised as a potential inhibitor of hepatitis C virus through interfering with the interactions between HCV glycoprotein E2 and the host entry factor CD81. Compound 9 inhibited cell culture-derived HCV and HCV pseudo-particles with the IC 50 of 0.325 and 0.259 μg/mL [61]. …”