CADD

Virtual Screening of Natural Compounds against Shigella and other WHO priority pathogens for identifying potential leads for drug and vaccine design

Shigellosis is a type of food poisoning caused by infection with the Shigella species. It is a major public health problem in developing countries where sanitation is poor. Shigellosis is spread by means of fecal-oral transmission. It is one of the most common disorders specially affecting children in West Bengal. Infection is initiated by ingestion of shigellae. An early symptom, diarrhoea (possibly elicited by enterotoxins and/or cytotoxin), may occur as the organisms pass through the small intestine. The hallmarks of shigellosis are bacterial invasion of the colonic epithelium and inflammatory colitis. These are interdependent processes amplified by local release of cytokines and by the infiltration of inflammatory elements. Colitis in the rectosigmoid mucosa, with concomitant malabsorption, results in the characteristic sign of bacillary dysentery: scanty, unformed stools tinged with blood and mucus.Shigellosis occurs worldwide, and it tends to occur whenever war, natural calamities (eg, earthquakes, floods), or unhygienic living conditions result in overcrowding and poor sanitation. S boydii and S dysenteriae occur more commonly internationally. Disease from Shigella species causes an estimated 1 million deaths and 165 million cases of diarrhea annually worldwide. Severe dysentery is treated with ampicillin, trimethoprim-sulfamethoxazole, or, in patients over 17 years old, a 4-fluorquinolone such as ciprofloxacin. Vaccines are not currently available, but some promising candidates are being developed.

This project aims to identify potential natural compounds as leads for drug discovery trials through the process of virtual screening; as a method for management of the disease and arm the human race with a potential cure for this fatal disease.

Identification of potential lead compounds as inhibitors and convoy drugs against p - glycoprotein from Medicinally important plants Foeniculum vulgare (Fennel) and Trigonella foenum-graecum (Fenugreek) using De novo transcriptome analyses and virtual screening

Despite the available knowledge of the important chemical constituents and their possible health benefits as well as the components being a suitable convoy drugs; no reports are available regarding the testing of the active constituents either invite or computationally to understand their effects on p - glycoprotein inhibition and identification of the enriched pathways which result in the production of these chemicals.

This project attempts to investigate this gap in linking the traditional knowledge and identifying suitable phytochemicals for proposal as suitable convoy drugs effective against p - glycoprotein. The results of the analyses would enable the identification of a proper set of lead molecules against p - glycoprotein and also shed light on the actual pathways that regulate the production of the target phytochemicals of plant origin from Fenugreek and Fennel.

TEAM

Dr. Santanu Chakrabarti

Principal, GGDC Singur

Ms. Sarmistha Mukhopadhyay (WBDST - SRF)

Guest Scholar: Ms. Arunima Bhattacharya