Pharmacologyonline 3: 64-72 (2006)

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ROLE AND SCOPE OF ETHNOMEDICAL PLANTS IN THE DEVELOPMENT OF ANTIVIRALS

Debprasad Chattopadhyay

ICMR Virus Unit, ID & BG Hospital, GB 4, First floor, 57 Dr. Suresh C Banerjee Road, Beliaghata, Kolkata 700 010, India.

Summary Ethnomedicinal plants have been used as source of drugs for almost all diseases, but none are used against viruses probably because there are a very few specific viral targets for natural molecules to interact. Most of the available antiviral drugs often lead to side effects, viral resistance, recurrence and latency. A wide range of ethnomedicinal plants showed strong antiviral activities either by inhibiting replication, or genome synthesis of many viruses. Hence, development of new antivirals from natural source is an alternate approach. This review will discuss some of the promising antivirals of ethnomedicinal plants with proven in vitro and some documented in vivo activities. Keywords: Ethnomedicines; Antivirals, HSV; HIV.

People of all continents have long used poultices and infusions of indigenous plants like cedar wood and cypress oil, juice of licorice, myrrh and poppy for the treatment of coughs and colds to parasitic infections and inflammation1. The clinical virologists are looking into the antiviral plant extracts as (i) the effective life span of antiviral drug is limited; (ii) many viral diseases are intractable to most of the orthodox antivirals, (iii) development of viral resistance, latency and recurrence, and (iv) rapid spread of emerging and reemerging viral diseases like HIV/AIDS, SARS etc. All these spurred intensive investigation into the ethnomedicines, especially for people unable to afford expensive antivirals, and the impressive array of knowledge and wisdom of indigenous people about their generation old medicaments for the development of new or complementary antivirals. 64

Pharmacologyonline 3: 64-72 (2006)

Newsletter

Chattopadhyay

Viral infections can be controlled either by prophylactic or therapeutic measures. As metabolically inert particle viruses require living cells to replicate and hence, it is difficult to design a treatment that attacks the virion without affecting the host. Although there are 37 licensed antivirals, the development of antivirals from natural source is less explored because of a very few specific viral targets for natural molecules to interact with. Fortunately, many viruses have unique features in their structure or replication cycles that can be the potential targets, e.g., the nucleoside analogue acycloguanosine that blocks key enzymes of herpes virus replication2. Due to the amazing structural diversity and broad range of bioactivities many ethnomedicinal plant extracts inhibit several steps of replication or certain cellular factors of many DNA and/or RNA viruses. This review will summarize some of the prospective molecules of ethnomedicinal plants, active against diverse virus families. A list of some potential ethnomedicinal plants and their antiviral principles are presented in Table 1. Major group of antivirals of Ethnomedicinal plants Phenolics: Phenolics are the simplest bioactive phenylpropanes with wide range of antiviral activities. The oligophenols of Peruvian folklore Stylogne cauliflora inhibit hepatitis C virus (HCV) non-structural serine protease3, while polyphenols of Agrimonia pilosa and Punica granatum had anti-herpes simplex virus (HSV) type 1 activity; but the polyphenols of Blumea laciniata and Scutellaria indica inhibit respiratory syncytial virus (RSV) with IC5012.5-32 µg/ml4. The caffeic acid, chlorogenic acid and rosmarinic acid derivatives of Plantago major, an ethnomedicine of Asia, inactivate HSV-1 and HSV-25, varicella zoster virus (VZV), pseudorabies virus (PRV) and influenza viruses (IV)4, that can be developed as antiherpes agent. The phenolics inactivate cell surface proteins, prevent viral adsorption, inhibit viral reverse transcriptase (RTase) and RNA polymerase, and the structure activity study revealed that the sites and number of OH- on phenols are responsible for their antiviral activity. The proanthocyanidin A1 had remarkable anti-herpes activity that block HSV2 attachment and penetration6, while procyanidin C1 inhibit HIV-17. The anti-HSV activity of epicatechin dimers is due to ortho-trihydroxyl groups and the double interflavan linkages5, while xanthohumol of Humulus lupulus might serve as a lead for anti-HSV agent7. The bis-catechol l-chicoric acid, a dicaffeoyltartaric acid (DCTA), is the most active inhibitor of HIV integrase and envelope gp1208. Similarly, the curcuminoids of Indian spice Curcuma longa inhibit Tat-mediated gene expression, integrase, protease and virus-cell fusion of HIV-18. Coumarins: Coumarins are phenolics with fused benzene and α-pyrone rings. They can stimulate macrophages and thereby exert an indirect effect on viral infections. The oral anticoagulant warfarin prevents recurrences of cold sores caused by HSV-19; while 65

Pharmacologyonline 3: 64-72 (2006)

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Chattopadhyay

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