1. KAUTIR (Kerala Agricultural University Theses Information and Retrieval)
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Item Evaluation of anti-tuberculosis activity in selected vegetable crops: Garlic, Onion and Drumstick(Department of Plant Biotechnology, College of Agriculture, Vellayani, 2019) Nandu Mohan; Biju, C KTuberculosis (TB) is the second worldwide killer infectious disease caused by Mycobacterium tuberculosis (TB). Globally it kills 1.8 million people annually and 40,000 from India. Current TB treatment is based on principles of combination chemotherapy which takes prolonged period. Most of the anti-TB drugs are good old discoveries and now they are resistant to new strains of TB. The emergence of multi drug resistant (MDR) and extensively drug resistant (XDR) mutants and the adverse effect to immune system in patients co-infected with HIV are the major hurdles in the TB treatment. Thus the discovery of new vaccines and novel drugs become the need of the hour. History shows the practice of several herbal combinations that have been using traditionally from the ancient civilizations against tuberculosis. Many indigenous vegetable crops of Kerala are having anti-TB properties but its efficacies and the pharmacological action are not yet scientifically investigated. In the present study the phytomolecules reported from Allium cepa, Allium sativum and Moringa oleifera were screened through in silico methods. Decaprenylphosphoryl-beta-D-ribose epimerase (DprE1) protein was selected as the target molecule for doing the in silico docking analysis. DprE1 is an enzyme responsible for the synthesis of arabinan, the virulent factor in Mycobacterium, tuberculosis. The 3-D structure of the molecule was retrieved from PDB (PDB id 4FDO) and the active site DprE1 was detected using the tool PDBsum. Information regarding the chemical molecules reported in the selected spices was collected through literature survey and databases. A total of 175 phytochemicals (Allium cepa – 81, Allium sativum – 52 and Moringa oleifera – 42) were screened. The selected phytochemicals were docked against DprE1 protein using AutoDock 4.2. The docked structures having ΔGbind ≤ -5 kcal/mol-1 were selected as best hit molecules. To nullify the errors in lead identification the top ranked hit molecules were again docked using the tools Hex server, iGEMDOCK, FireDockand SwissDock. The docked results were statistically analyzed following DST and Zhang rule and selected the top ranked molecules viz. 24-Methylenecycloartanol (A.cepa), Kaempferol & Quercetin (A. sativum & M. oleifera) and 4-hydroxymellein from M. oleifera. All the four compounds have been subjected for bioactivity and druglikness score using Molinspiration and MolSoft tools. The ADMET property study was done by using the tool pkCSM. Kaempferol, Quercetin and 4-hydroxymellein showed acceptable range in both bioactivity analysis and in ADMET property prediction. Overall study substantiate that Moringa stands first in the evaluation as it produce all the three sought out leads followed by garlic with two leads. Theoretical prediction of drug likeliness only gives probability and its activity in a biological system. Therefore, in vitro & in vivo studies and in-depth clinical trials are necessary for developing a drug out of the lead molecules.Item In silico screening and identification of lead molecules with anti-hepatitis B activity(Department of Plant Biotechnology, College of Agriciulture, Vellayani, 2018) Alina A Nazir; Sreekumar, SHepatitis B is an infectious liver disease which causes high morbidity and mortality worldwide. The present treatment of chronic hepatitis B (CHB) infection concentrates on clearing the HBV DNA and to prevent the development of complications. Currently seven drugs are available for the treatment of CHB: 5nucleo(S)tide analoque and 2 interferon based therapies. In order to find out safe and better drug, in the present investigation a total of 571 phytochemicals from three plants viz Elettaria cardamomum (L.) Maton, Curcuma longa and Zingiber Officinale were screened against three Hepatitis B Virus proteins such as HBx, HBc and polymerase (Poly) through docking using the tool AutoDock 4.2. For docking out of 571 phytochemicals derived from E. cardamomum (87), Z. officinale (273) and C. Longa (211), the structure of 558 compounds were downloaded form chemical databases and remaining 13 molecules structures were drawn using ChemSketech. The 3D structures of all phytochemicals structures were generated using the tool CORINA in .pdb format. The 3D structure of the target protein HBc was retrieved from Protein Data Bank (PDB ID:1QGT) and the structure of HBx and poly were modelled using the software MODELLER. The active site and residues of the target protein HBx and HBc was detected using PDB Sum and Poly was detected using CASTp. Docking was performed using the tool Auto Dock and the docked structures having binding energy <-5.0 kcal/mol were considered as the active/hit molecules. Top ranked five hit molecules with least binding energy obtained from each plant were further analysed based on other ctiteria such as hydrogen bond, other molecular interactive forces like hydrophobic interactions and drug likeness properties and selected the best lead molecules. The result showed that all three spices have inhibitory effect on the targets, HBX,HBc and poly. The best lead molecules selected against HBX was B-carotien (G bind <-11.40 kcal/mol) derived from Z.officinale and C. longa follewed by B-sitosterol (Gbind <-8.62 kcal/m0l) which was present in all the three plants. Similarlly, the best lead obtained against HBc was -ylangene (Gbind <-8.04 kcal/mol) from C. longa and Z.officinale and the compound 2-hydroxy methyl anthraquinone (-Gbind < -8.00 kcl/mol) present in E.cardamomum was also equallly competent as the best lead. Against polymerase vanilic acid (Gbind <-5.50 kcal/mol)was found as the best lead and it was present in all three plants. The compound p-hydroxy-benzoicacid obtained from Z. officinale and protocatechuic-acid from C.longa were also equally competent as the best lead. The results support the traditional knowledge and practice. However, based on the foregoing results in vitro and in vivo experiments are to be essential for further confirmation.