Novel inhibitor to combat kala-azar identified: 

Novel inhibitor to combat kala-azar identified: 

Context

• Scientists have been able to identify a FDA-approved molecule that shows enhanced anti-kala-azar activity by combining structure-based drug designing methodology

What is kala-azar?

• Visceral leishmaniasis (VL) as kala-azar is the most severe form of leishmaniasis and, without proper diagnosis and treatment, is associated with high fatality.
• This disease is the second-largest parasitic killer in the world responsible for an estimated 200,000 to 400,000 infections each year worldwide
• One active inhibitor molecule showed the highest stability in binding to the active sites of the target enzyme which helps in the formation of glycoprotein, beta-Galf.
• After binding to the UGM, the molecule inhibits the enzyme activity thereby reducing the virulence, parasite survival and transmission of disease.

What is the treatment available for Kala-azar?

• Treatment for kala-azar is limited due to high toxicity to human cells, low efficacy of the drug, high cost and drug resistance making the development of novel anti-kala-azar drugs a priority.
• How deep-rooted is the disease in India?
• India has around 3,000 people afflicted with kala-azar, accounting for 50% of the global burden. It is endemic in West Bengal, Bihar, Jharkhand and eastern Uttar Pradesh.

What is Beta-Galf?

• Beta-Galf is a major cell surface component of Leishmania parasite and is responsible for the virulence of the pathogens and plays an essential role in parasite survival and transmission of disease.
• Beta-Galf is also found in Mycobacterium tuberculosis that causes TB and Trypanosoma cruzi parasite that causes sleeping sickness but is absent in humans.
• Like beta-Galf, the UGM enzyme is also absent in humans but is critical for the biosynthesis of beta-Galf thereby making the UGM enzyme an attractive drug target.

What was the observation?

• One of the three chosen inhibitors was evaluated in vitro for anti- Leishmania activity and found to significantly inhibit the growth of Leishmania donovani.
• Different doses of the compound were tested and the minimum inhibitory concentration or IC50 value (the lowest concentration of the compound required to inhibit the visible growth of a pathogen) was found to be 50 microgram per litre.