The Drug Controller General of India (DGCI) has recently given its approval to the Council for Scientific and Industrial Research (CSIR) for conducting clinical trials on medicinal plant Cocculus hirsutus and antiviral drug favipiravir to treat coronavirus patients.
Favipiravir is a synthetic drug used to treat influenza, and targets a very broad spectrum of RNA polymerase. It is currently available in Japan, China and a few other countries as a well-known antiviral drug.
While the approval for Favipiravir is certainly an interesting development, the drug controller’s permission to test a purified fraction of a medicinal plant, Cocculus hirsutus, as a biological medicine or phytopharmaceutical is pathbreaking.
Cocculus hirsutus is a native herb used by tribes in this country. It was already under investigation as a medicine for dengue. Now, based on scientific data presented on quality and safety, it has been officially approved for clinical trials to test its efficacy as an “add-on drug” in mild cases to combat COVID-19.
Phytopharmaceuticals are essentially herbal medicine extracted from plants. They are a cocktail of different compounds, but have a biological origin from a plant. The Food and Drug Administration (FDA) of the United States calls them botanical drugs. Plant extracts and purified fractions need to be reviewed for quality, safety and efficacy differently from synthesised compounds or New Chemical Entities (NCEs). Indian drug laws were amended to create a new category of drugs called “phytopharmaceuticals” in 2015.
Sinnococculine- the workhorse
A purified fraction of the stem of Cocculus hirsutus (Fam. Menispermaceae) has been standardised for four marker compounds, a requirement for the definition of a phytopharmaceutical. Sinnococculine is one of these compounds and is considered the bioactive moiety. This was earlier investigated for its activity against the virus causing dengue fever.
It was found to show antiviral activity on all the four serotypes of the dengue virus. Since it has strong antiviral
activity against the dengue virus, it may work against coronavirus since the mode of replication inside the body is similar.
COVID-19 is known to infect through the endosomal pathway for post-entry intracellular processing, which leads to immune activation via an increase in pro-inflammatory cytokines. Cocculus hirsutus (CH) indicates an inhibition of replication post entry into endosomes and a decrease in excessive immune activation when tested during investigations against dengue. It is hypothesised to potentially work through this mechanism in case of COVID-19, but needs to be confirmed via investigations in humans post standardisation and safety data generation. The Centre for Drugs Standard Control Organisation (CDSCO), India’s drugs regulator, considered and accorded permission to test the CH fraction in mild patients of COVID-19.
The drug development process is typically arduous, time-consuming and expensive. It takes anywhere between 10 and 15 years and an investment of several billion dollars for taking a drug from the research level to the market. As we know, in the last decade, NCE pipelines have dwindled, many drugs that were launched met with post-marketing troubles, and some had to be withdrawn.
Plant-based drugs—the future?
In this context, scientists and research-oriented drug makers are looking very keenly at plant-based drug leads as the future. Although it is a known fact that about 60% of the NCEs have come from one or the other plants as a source of the chemical, the move to start working on a pure compound isolated from plants or purified plant extracts/fractions is an interesting development. Nevertheless, it is also obvious as an evolutionary process in the new context.
The US FDA has recently issued marketing authorisation to a topical cream containing standardised green tea extract as a US botanical drug for treating genital warts, and also to an extract of Dragon Blood Tree of South Africa for treating diarrhoea induced by anti-HIV drugs after evaluating the respective Investigational New Drug Applications.