{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T06:37:27Z","timestamp":1764225447448,"version":"3.40.4"},"reference-count":48,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2018,5,15]],"date-time":"2018-05-15T00:00:00Z","timestamp":1526342400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["BT\/PR23317\/MED\/29\/1186\/2017"],"award-info":[{"award-number":["BT\/PR23317\/MED\/29\/1186\/2017"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Emergence of multi\u2010drug resistance tuberculosis has become a serious health problem globally. Accumulation of mutations in the drug target led to the development of multi\u2010drug resistant mycobacterial strains that have made most of the conventional drugs ineffective. Hence, there is desperate need for the development of new therapeutic strategies. Here, we focused on the analysis of mutations in <jats:italic>Mycobacterium tuberculosis<\/jats:italic> (<jats:italic>Mtb<\/jats:italic>) PncA (pyrazinamidase) that is responsible for resistance against first\u2010line anti\u2010tuberculosis pyrazinamide (PZA) drug. First, PZA and its two isoforms were analyzed for their binding affinity toward ligand binding cavity of <jats:italic>Mtb<\/jats:italic> wild\u2010type and mutant PncA proteins. The observations suggested that some drug resistant mutations cause strong binding of PncA with the active form of PZA and impair its release, which is required to inhibit the growth of <jats:italic>Mtb<\/jats:italic>. To improve the treatment of PZA resistant <jats:italic>Mtb<\/jats:italic>, high throughput virtual drug screening was performed to identify potent drug molecules from a library of compounds derived from ChEMBL database. From this library, we predicted a lead molecule (terta\u2010butyl(2S,4S)\u20104\u2010amino\u20102\u2010cyclopropyl\u20106\u2010(trifluoromethyl)\u20103,4\u2010dihydro\u20102H\u2010quinoline\u20101\u2010carboxylate) to be more effective against PZA resistant <jats:italic>Mtb<\/jats:italic> strains in comparison to PZA. The lead molecule showed better drug\u2010like properties such as high affinity and atomic interactions with wild\u2010type and drug\u2010resistant mutations in <jats:italic>Mtb<\/jats:italic> PncA proteins. Further, molecular dynamic simulation studies showed that this lead molecule has better conformational stability and compatibility with drug\u2010resistant PncA proteins in comparison to PZA drug. We hypothesized that the predicted lead compound could be more effective, and thus may improve the treatment of PZA resistant tuberculosis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcb.27033","type":"journal-article","created":{"date-parts":[[2018,5,15]],"date-time":"2018-05-15T12:12:00Z","timestamp":1526386320000},"page":"7328-7338","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Computational discovery of potent drugs to improve the treatment of pyrazinamide resistant <i>Mycobacterium tuberculosis<\/i> mutants"],"prefix":"10.1002","volume":"119","author":[{"given":"Manaswini","family":"Jagadeb","sequence":"first","affiliation":[{"name":"School of Biotechnology KIIT University Bhubaneswar Odisha India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Surya N.","family":"Rath","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics Orissa University of Agriculture and Technology Bhubaneswar Odisha India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9596-2629","authenticated-orcid":false,"given":"Avinash","family":"Sonawane","sequence":"additional","affiliation":[{"name":"School of Biotechnology KIIT University Bhubaneswar Odisha India"},{"name":"Centre for Bioscience and Biomedical Engineering IIT Indore Simrol Madhya Pradesh India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,5,15]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jis381"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4001"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-016-2083-4"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)32071-2"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)62675-6"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.3201\/eid0402.980207"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1086\/515362"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2002.03162.x"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1466"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.02499-08"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.4.1075-1077.2000"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.1996.tb08515.x"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0004540"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1590\/S0074-02762009000300012"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0133869"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.5588\/ijtld.15.0389"},{"key":"e_1_2_7_18_1","first-page":"6","article-title":"The curious characteristics of pyrazinamide: a review","volume":"7","author":"Zhang Y","year":"2003","journal-title":"Int J Tuberc Lung Dis"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2012.759885"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.3.636"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2011.10.024"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1996.0897"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkl282"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.26420"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.3346\/jkms.2001.16.5.537"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.3.636"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkm054"},{"key":"e_1_2_7_28_1","first-page":"802","article-title":"Frequency and implications of pyrazinamide resistance in managing previously treated tuberculosis patients","volume":"10","author":"Louw GE","year":"2006","journal-title":"Int J Tuberc Lung Dis"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.43.7.1764"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.12.3298-3301.2000"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkr777"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/1758-2946-3-33"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1996.0897"},{"key":"e_1_2_7_34_1","unstructured":"AbrahamMJ Van Der SpoelD LindahlE HessB. The GROMACS development team. GROMACS user manual version.2014;5."},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444904011679"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.445869"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-987X(199709)18:12<1463::AID-JCC4>3.0.CO;2-H"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.2408420"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.328693"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.470117"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0606843103"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1004277"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(63)80023-6"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1515\/bmc.2010.022"},{"key":"e_1_2_7_45_1","first-page":"181","volume-title":"Computation of Protein Geometry and its Applications: Packing and Function Prediction","author":"Liang J","year":"2007"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.4172\/jcsb.1000103"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-409X(00)00129-0"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.12921\/cmst.2012.18.02.81-88"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm060642i"}],"container-title":["Journal of Cellular Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcb.27033","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcb.27033","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcb.27033","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcb.27033","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T19:12:23Z","timestamp":1744917143000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcb.27033"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5,15]]},"references-count":48,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2018,9]]}},"alternative-id":["10.1002\/jcb.27033"],"URL":"https:\/\/doi.org\/10.1002\/jcb.27033","archive":["Portico"],"relation":{},"ISSN":["0730-2312","1097-4644"],"issn-type":[{"type":"print","value":"0730-2312"},{"type":"electronic","value":"1097-4644"}],"subject":[],"published":{"date-parts":[[2018,5,15]]},"assertion":[{"value":"2017-12-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-04-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-05-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}