Tryptanthrin – Unexplored promise?September 5, 2020 0 By FM
The novel, Kurinji Flowers, by Clare Flynn narrates a tragic love affair in 1940s India in the backdrop of Neelakkurinji flowers. Scientifically known as Strobilanthes kunthiana, Neelakkurinji blooms only once in twelve years and dies. The seasonal flowering of the purplish-blue flowers has even imparted the name Nilgiris — or blue mountains — to its abode. Another species, Strobilanthes cuspidatus, blooms once every seven years. The genus Strobilanthes, a member of the family Acanthaceae, was first described by Christian Gottfried Daniel Nees von Esenbeck in the 19th century. The genus is estimated to hold around 350 species, of which about 46 are found in India. Most of these species show unusual flowering behaviour.
So much for Strobilanthes’ contribution to the floral wealth of India. Now, it has become even more priceless: A compound from a species of Strobilanthes can be used to treat infections involving various coronaviruses.
The outbreak of SARS-CoV-2 and the widespread deaths caused by it all over the world have given a strong impetus to the scientific community to develop potential drugs to combat coronavirus disease-19 (COVID-19). In this context, this finding — which is also related to the Coronavirus family — offers a new ray of hope for the development of a suitable antiviral drug for use in this pandemic.
According to a paper published in journal Biomolecules (2020, 10, 366) by Yu-Chi Tsai et al. of Department of Biotechnology at Asia University in Taiwan, the biomolecule tryptanthrin isolated from the leaves of Strobilanthes cusia or Assam Indigo — a related plant — can act against certain human coronaviruses. Strobilanthes cusia (Nees) Kuntze is widely distributed in northeast India, Bangladesh, southern China, the Himalayan region, Myanmar, and Taiwan. The roots of Strobilanthes cusia (named ‘Nan-Ban-Lan-Gen’ in Chinese) has been commonly used to treat infections by respiratory virus, such as influenza viruses, the mumps virus and severe acute respiratory syndrome (SARS) coronavirus. The leaves of Strobilanthes cusia (Assam Indigo, Chinese Rain Bell) is generally used for the production of indigo dyes. However, the leaves contain active chemical components with antibacterial, anti-inflammatory and anti-tumor properties, including tryptanthrin (6,12-dihydro-6,12-dioxoindolo-(2,1-b)-quinazoline). Similarly, another constituent, Indirubin, modulates influenza A virus-induced inflammation and has been suggested as an antiviral and immunomodulatory agent against influenza A virus infection.
Of particular note is its effect on human coronavirus NL63 (HCoV-NL63), which shares many characteristics with the COVID-19 virus.
Like the COVID-19 virus, HCoV-NL63 is also an enveloped virus with a single-strand, positive-sense RNA genome, with a length of nearly 26-32 kb. The spike protein, the major envelope protein of HCoV-NL63, specifically binds to the zinc peptidase angiotensin-converting enzyme 2 (ACE2) which has also been identified as the receptor for both the SARS and the COVID-19 viruses. HCoV-NL63 infections are prevalent during spring and winter seasons in temperate countries. HCoV-NL63 is primarily associated with immunocompromised patients with respiratory illnesses, young children and the elderly. HCoV-NL63 has become one of the primary pathogens in respiratory viral diseases. However, there are no effective antivirals for it.
The magic molecule
Tryptanthrin is one of the most important members of indoloquinoline alkaloids. This alkaloid exhibits diverse biological effects, such as antimicrobial, antitumour, and anti-inflammatory properties. Tryptanthrin has been used as a Chinese medicine and a folk medicine for its anti-inflammatory, antipyretic and analgesic effects. The natural product tryptanthrin is a weakly basic alkaloid. The name tryptanthrin is derived from the observation that this compound is produced by the yeast Candida lipolytica from which it was isolated as an indoloquinazoline alkaloid. However, tryptanthrin was first reported as a sublimation product of indigo under reduced pressure before being isolated from Candida lipolytica. Later, Tryptanthrin was synthesised continuously from petroleum. It is also isolated from a number of plant families, animals and microorganisms, such as batracylin, (-)-vasicine and luotonin. As per Sigma-Aldrich, Tryptanthrin blocks leukotriene production in neutrophils and in whole blood assays, and was also proven in an in vivo rat model. The compound also inhibits P-glycoprotein and sensitises resistant cancer cell lines to elimination by cytotoxic agents.
In addition to Strobilanthes cusia, tryptanthrin is found in a number of other plants such as Isatis, Calanthe, Couroupita and Wrightia. Among these Wrightia tinctoria is more common in Kerala.
A promise for the future
The present study by Yu-Chi Tsai et al. was the first to demonstrate the antiviral efficiency of Strobilanthes cusia leaf against HCoV-NL63. The leaf extract significantly reduced progeny virus production and inhibited viral infectivity. Notably, tryptanthrin and indigodole B exhibited strong virucidal activity as well. This study identified tryptanthrin as the key active component of S. cusia leaf methanol extract that acted against HCoV-NL63 in a manner that is independent of cell types. The results reveal that tryptanthrin possesses antiviral potential against HCoV-NL63 infection. Previous studies have revealed several active antiviral compounds in the Strobilanthes cusia extract effective against Herpes simplex virus-1 and influenza A virus. Thus, tryptanthrin, exhibiting the virucidal action and impeding post-entry replication, might be developed as one of the first hit compounds against human coronaviruses. This points towards a promising, but untapped, treatment possibility for coronavirus diseases sourced from our extensive floral wealth.
However, Tryptanthrin has not yet been reported from Strobilanthes kunthiana or allied species. Such efforts, however, could yield promising results.
The author is Science Writing Fellow, Kerala State Council for Science, Technology and Environment, Govt. of Kerala.