Drug resistance has mushroomed up after advent of every major class of antimicrobial drugs, varying in time from as short as 1 year (penicillin) to >10 years. Organisms associated with nosocomial and community acquired infections are also becoming drug resistant due to the over utilization of antibiotics, consequently leading to high morbidity, mortality and increased health costs. One such example of a beta lactamase producing bacteria is New Delhi Metallo beta lactamase (NDM-1) producing Escherichia coli and Klebsiella pneumoniae, and was reported for the first time in the year 2009 in a Swedish patient. NDM-1 bacterial strains possess more potent hydrolysis ability towards almost all antibiotics, including Carbapenems. NDM-1 bacterial strains are sensitive to Tigecycline and Colistin but there is problem of side effects associated with them. In such a situation where NDM-1 strains are displacing antibiotic sensitive strains and are resistant to most of the chemotherapeutic agents, there is a need for the search of novel alternative effective therapeutic agents. The present bioprospective study aims to analyze the potential of various natural plants or their products, based upon bioactivity parameters and presence of chemical constituents, using matrix based modeling, followed by optimization. The outcomes of the lead identification need verification with respect to antimicrobial potential against virulent NDM-1 Escherichia coli.