Abstract

BackgroundDevelopment of new and effective therapeutics for sexually transmitted herpes simplex virus-2 (HSV-2) infection is important from public health perspective. With an aim to identify natural products from medicinal plants, in the present study, the potential of Terminalia chebula Retz was investigated for its activity against HSV-2.MethodsFruits of Terminalia chebula Retz were used to prepare 50% ethanolic extract. In addition, chebulagic acid and chebulinic acid both purified from T. chebula were also used. The extract as well as purified compounds were first used to determine their in vitro cytotoxicity on Vero cells by MTT assay. T. chebula extract, chebulagic acid, chebulinic acid along with acyclovir were subsequently assessed for direct anti-viral activity, and their ability to inhibit attachment and penetration of HSV-2 to the Vero cells. In addition, their anti-HSV-2 activity was also determined by in vitro post-infection plaque reduction assay.ResultsCytotoxicity assay using Vero cells revealed CC50 = 409.71 ± 47.70 μg/ml for the extract whereas chebulagic acid and chebulinic acid showed more than 95% cell viability up to 200 μg/ml. The extract from T. chebula (IC50 = 0.01 ± 0.0002 μg/ml), chebulagic (IC50 = 1.41 ± 0.51 μg/ml) and chebulinic acids (IC50 = 0.06 ± 0.002 μg/ml) showed dose dependent potent in vitro direct anti-viral activity against HSV-2. These also effectively prevented the attachment as well as penetration of the HSV-2 to Vero cells. In comparison, acyclovir showed poor direct anti-viral activity and failed to significantly (p > 0.05) prevent the attachment as well as penetration of HSV-2 to Vero cells when tested upto 50 μg/ml. However, in post-infection plaque reduction assay, T. chebula extract, chebulagic and chebulinic acids showed IC50 values of 50.06 ± 6.12, 31.84 ± 2.64, and 8.69 ± 2.09 μg/ml, respectively, which were much lower than acyclovir (71.80 ± 19.95 ng/ml).ConclusionsThe results presented herein suggest that T. chebula extract, chebulagic and chebulinic acids have higher direct antiviral activity against HSV-2 and efficacy to inhibit virus attachment and penetration to the host cells as compared to acyclovir. However, acyclovir is more potent to inhibit post-infection virus replication. Hence, T. chebula may be a useful candidate for developing alternative therapy for prevention of sexually transmitted HSV-2 infection.Graphical abstractᅟ

Highlights

  • Development of new and effective therapeutics for sexually transmitted herpes simplex virus-2 (HSV2) infection is important from public health perspective

  • T. chebula may be a useful candidate for developing alternative therapy for prevention of sexually transmitted Herpes simplex virus (HSV)-2 infection

  • Keeping in view of the above, the 50% ethanolic extract prepared from the fruits of T. chebula was evaluated for direct anti-viral activity and its impact on the attachment and penetration of the Herpes simplex virus-2 (HSV-2) to the Vero cells

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Summary

Introduction

Development of new and effective therapeutics for sexually transmitted herpes simplex virus-2 (HSV2) infection is important from public health perspective. Herpes simplex virus-2 (HSV-2) is a double stranded DNA virus belonging to the family Herpesviridae. It causes genital herpes, contributing to the risk of HIV infection through sexual route [1, 2]. Since virus is an intracellular parasite in neural ganglia, it is difficult to completely eliminate it [1, 4]. Nucleoside derivatives such as acyclovir, valaciclovir, famciclovir and cidafovir have been widely used for the treatment of HSV infection [5]. In addition to high cost, treatment with acyclovir and other related drugs is associated with the emergence of drug resistant strains [6], which is a major hurdle in the immunocompromised individuals, co-infected with other opportunistic Sexually Transmitted Infections (STIs) such as HIV-1 [7, 8]

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