IN SILICO PREDICTION OF RIBOSWITCH AS A POTENTIAL DRUG TARGET AND DESIGN OF ITS OPTIMAL INHIBITORS AND PHARMACOPHORE FOR BACILLUS CEREUSAbstract
Bacillus cereus is a gram-positive, rod-shaped, motile, beta hemolytic bacteria. These bacteria cause foodborne illness, severe nausea, vomiting, diarrhea, and keratitis. Foodborne illness caused by Bacillus cereus occurs because of the bacterial endospores survival in improperly cooked food. The bacteria produce enterotoxins having high resistance against heat and acids, and they cause the diarrheal and emetic syndrome. The diarrhetic syndromes observed in patients are thought to stem from the three toxins: hemolysin BL (Hbl), non-hemolytic enterotoxin (Nhe) and cytotoxin K (CytK). These enterotoxins are all produced in the small intestine of the host, thus thwarting digestion by endogenous host enzymes. The effect is the loss of cellular membrane potential and eventually cell death. Antibiotics that are used for the treatment of infectious disease have suffered a major setback due to the development of drug resistance by the pathogenic target organism. Therefore, in the current study, the riboswitches are explored as an alternative potential drug target. A riboswitch of Bacillus cereus bacteria has been identified as a drug target, and an inhibitor is designed with the help of molecular docking and simulation based virtual screening. Based on the in-silico studies, the designed Lead 1 molecule is recommended as a potential inhibitor for riboswitch of Bacillus cereus. The proposed inhibitor is superior over the existing antibiotics as it has less side effects and remote chances of development of resistance by the pathogen.