Antiviral potential and mode of action of Indigofera heterantha against HSV-2 by targeting the early stages of infection.

ABSTRACT

BACKGROUND: The development of antivirals against herpes simplex virus 2 (HSV-2) has a major public health importance because of the wide spectrum of associated clinical disease in both immunocompetent and immunocompromised populations. Even with the extensive use of acyclovir, issues such as emergence of drug-resistant strains, poor oral bioavailability and low effectiveness in recurrent infections have highlighted the requirement for alternate therapies. Plants, which are rich in metabolites and active against viruses, are being explored as one such source. We had earlier reported specific and potent anti-HSV-2 activity from the roots of the plant Indigofera heterantha. Herein, we describe the mechanism by which it exerts this antiviral potential against HSV-2. METHODS: MTT, plaque reduction and immunofluorescence techniques were used for in vitro antiviral studies. Animal studies were carried out in HSV-2-infected mice followed by plaque reduction assays. RESULTS: The extract was found to act at multiple steps of viral entry viz attachment, adsorption and penetration by blocking binding sites present on the viral envelope glycoproteins which eventually blocks its binding with the cell surface receptors present on the host cells. We also showed efficacy of PP9706642 topical application in prohibiting HSV-2 invasion to nearby organs from the site of infection, that is vagina in HSV-2 infected animals. CONCLUSIONS: The extract targets the early and late stages of HSV-2 viral life cycle and thus shows great promise as both a prophylactic as well as therapeutic phytopharmaceutical against HSV-2.