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Control of herpesvirus infection
Debprasad Chattopadhyay et al.
The herpesvirus causes a lifelong infection with high morbidity, and is under-diagnosed due to its mild and asymptomatic nature. HSV alone affects more than one third of the world's population1 and is responsible for a wide array of human disease, with effects ranging from discomfort to death. Before the 1970s, when acyclovir (ACV) was introduced as an antiviral drug, cutaneous HSV infection was managed with drying agents and other local care. Newer antiviral drugs with once-daily dosage benefits have emerged during the past several years. Famciclovir and valacyclovir offer effective and convenient therapeutic choices but are often more expensive than acyclovir. Although no cure is available till date, nucleoside analogues acyclovir [9-(2-hydroxyethoxymethyl) guanosine], is widely used, as it selectively phosphorylated by thymidine kinase (TK) enzyme in infected cells. However, acyclovir-resistant herpesvirus was isolated in immunocompromised patients. Moreover, acyclovir is not suitable in neonatal infections and the infections caused by other members of Herpesviridae [Habif, 2004]. Therefore, new antiherpesvirus agents that can substitute or complement acyclovir group of drugs are highly desirable. Several herbal medicinal products are potential sources of functional foods and have various bioactivities like immunomodulatory and antitumor functions. Although the development of antiherpetic agents from herbal source is less explored probably because there are a very few specific viral targets for small natural molecules to interact with. However, several studies showed that phloroglucinol [Arisawa et al., 1990], anthraquinones [Sydiskis et al., 1991], polysaccharides [Marchetti et al., 1996], triterpenes and saponins [Simõnes et al., 1999], and polyphenols [Kuo et al., 2002; Chattopadhyay & Naik, 2007] isolated from several plants inhibit the replication of herpesviruses. A large number of plant-derived and synthetic antiherpes virus agents have also been described [Ferrea et al., 1993; Bourne et al., 1999; Ikeda et al., 2000; Jassim & Naji, 2003; Chattopadhyay & Khan, 2008] and several works is in progress to identify plants and their active components having anti-herpesvirus activity with an aim to prevent the transmission of sexually transmitted infections (STI’s), as well as to develop complementary antiherpes virus agent. A topical preparation from Glycyrrhiza glabra (liquorice root) containing triterpene glycyrrhetinic acid (Glycyrrhizin) used for the prevention and treatment of herpes outbreaks was found to inhibit acyclovir resistant HSV-1, by induction of CD4+ T cells [Utsunomiya et al., 1995]. Again oryzacystatin from rice plant (Oryzae sativa) showed in vitro and in vivo anti HSV-1 activity by inhibiting proteinase enzyme of herpesviruses [Aoki et al., 1995]. When 19 plant-derived compounds were tested by plaque reduction assay against HSV-2, it was found that eugenol, cineole, curcumin and carrageenan lambda type IV (ED50 ≤ 7.0 mg/ml), provided significant protection (P < 0.05) in intravaginal HSV-2 infected mouse and guinea pigs [Bourne et al., 1999]. Interestingly a thiazolylsulfonamide