Browsing by Author "Gupta, R."

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    Rational design of drug-like compounds targeting Mycobacterium marinum MelF protein
    (Public Library of Science, 2017) Dharra, R.; Talwar, S.; Singh, Y.; Gupta, R.; Cirillo, J.D.; Pandey, A.K.; Kulharia, M.; Mehta, P.K.
    The mycobacterial mel2 locus (mycobacterial enhanced infection locus, Rv1936-1941) is Mycobacterium marinum and M. tuberculosis specific, which can withstand reactive oxygen species (ROS) and reactive nitrogen species (RNS) induced stress. A library of over a million compounds was screened using in silico virtual ligand screening (VLS) to identify inhibitors against the modeled structure of MelF protein expressed by melF of mel2 locus so that M. marinum?s ability to withstand ROS/RNS stress could be reduced. The top ranked 1000 compounds were further screened to identify 178 compounds to maximize the scaffold diversity by manually evaluating the interaction of each compound with the target site. M. marinum melF was cloned, expressed and purified as maltose binding protein (MBP)tagged recombinant protein in Escherichia coli. After establishing the flavin dependent oxidoreductase activity of MelF (~ 84 kDa), the inhibitors were screened for the inhibition of enzyme activity of whole cell lysate (WCL) and the purified MelF. Amongst these, 16 compounds could significantly inhibit the enzyme activity of purified MelF. For the six best inhibitory compounds, the minimal inhibitory concentration (MIC) was determined to be 3.4?19.4 ?M and 13.5?38.8 ?M for M. marinum and M. tuberculosis, respectively. Similarly, the minimal bactericidal concentration (MBC) was determined to be 6.8?38.8 ?M and 27?38.8 ?M against M. marinum and M. tuberculosis, respectively. One compound each in combination with isoniazid (INH) also showed synergistic inhibitory effect against M. marinum and M. tuberculosis with no cytotoxicity in HeLa cells. Interestingly, these inhibitors did not display any non-specific protein-structure destabilizing effect. Such inhibitors targeting the anti-ROS/RNS machinery may facilitate the efficient killing of replicating and nonreplicating mycobacteria inside the host cells. ? 2017 Dharra et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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    Vermitechnology for Organic Waste Recycling
    (Elsevier Inc., 2016) Gupta, R.; Garg, V.K.
    The disposal and management of solid wastes is a technical and ecological challenge throughout the globe because of their quantities and heterogeneous nature. Vermicomposting is one of the most ecologically and economically sound technologies for handling the biodegradable organic fraction of solid wastes. A large variety of such wastes of plant and animal origins can be gainfully vermicomposted at different scales varying from a household bin to a city level. Vermicompost also has excellent manurial properties as a soil conditioner and fertilizer, being a source of nitrogen, phosphorus, potassium, and other nutrients for plants. These virtues make vermicomposting a good option for processing the enormous quantities of biodegradable organic solid wastes that are generated in huge quantities. In this chapter, a review of the state of the art of vermicomposting technology is presented, including the process, various stages, characteristics, and benefits of vermicompost. ? 2017 Elsevier B.V. All rights reserved.