{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T06:08:09Z","timestamp":1788761289723,"version":"build-2803163510"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>\n                    Tuberculosis (TB), caused by\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    (\n                    <jats:italic>M.tb<\/jats:italic>\n                    ), remains a major global health challenge, necessitating the identification of novel drug targets with high specificity and therapeutic potential. Maltosyltransferase (GlgE) is a critical enzyme in the biosynthesis of cytosolic \u03b1-glucan, a key component required for maintaining cell wall integrity and intracellular survival of the pathogen. GlgE catalyzes the transfer of maltosyl units from maltose-1-phosphate to elongating \u03b1-glucan chains, and its inactivation results in toxic accumulation of metabolic intermediates, ultimately leading to bacterial death. Importantly, the absence of homologous pathways in humans underscores its suitability as a selective anti-tubercular (anti-TB) target. Sequence analysis of 382 clinical isolates demonstrated complete conservation of the\n                    <jats:italic>glgE<\/jats:italic>\n                    gene, highlighting its evolutionary stability and essentiality. Subsequently, structure-based virtual screening followed by molecular fingerprint clustering was performed to identify chemically diverse inhibitors. Twelve top ranked compounds (VMP-1 to VMP-12) were further evaluated through\n                    <jats:italic>in-vitro<\/jats:italic>\n                    antimycobacterial assays in broth culture and infected THP-1 derived macrophages, along with cytotoxicity assessment. Among these, VMP-7 exhibited significant inhibitory activity against\n                    <jats:italic>M.tb<\/jats:italic>\n                    at 12.5 \u03bcg\/mL, with minimal cytotoxic effects on host cells. Collectively, these findings validate GlgE as a highly conserved target and identify VMP-7 as a promising lead candidate for further preclinical development of novel anti-TB therapeutics.\n                  <\/jats:p>","DOI":"10.3389\/fmicb.2026.1909418","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T05:33:07Z","timestamp":1788759187000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Structure based discovery of VMP-7 as a promising GlgE targeting lead against Mycobacterium tuberculosis"],"prefix":"10.3389","volume":"17","author":[{"given":"Pratik","family":"Mahajan","sequence":"first","affiliation":[{"name":"Division of Molecular Biology, ICMR - National Institute of Translational Virology and AIDS Research, Pune","place":["Maharashtra, India"]},{"name":"Krishna Institute of Science and Technology, Krishna Vishwa Vidyapeeth (Deemed to be University), Karad","place":["Maharashtra, India"]},{"name":"Bioinformatics Centre, Savitribai Phule Pune University, Pune","place":["Maharashtra, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sushama","family":"Jadhav","sequence":"additional","affiliation":[{"name":"Division of Molecular Biology, ICMR - National Institute of Translational Virology and AIDS Research, Pune","place":["Maharashtra, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amitkumar","family":"Singh","sequence":"additional","affiliation":[{"name":"Experimental Animal Facility, ICMR-National Institute for Research in Tuberculosis (NIRT-JALMA, North India Campus), Agra","place":["Uttar Pradesh, India"]},{"name":"Academy of Scientific and Innovative Research, Ghaziabad","place":["Uttar Pradesh, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anupam","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"Academy of Scientific and Innovative Research, Ghaziabad","place":["Uttar Pradesh, India"]},{"name":"ICMR-National Institute of Virology, Pune","place":["Maharashtra, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manali","family":"Joshi","sequence":"additional","affiliation":[{"name":"Bioinformatics Centre, Savitribai Phule Pune University, Pune","place":["Maharashtra, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijay","family":"Nema","sequence":"additional","affiliation":[{"name":"Academy of Scientific and Innovative Research, Ghaziabad","place":["Uttar Pradesh, India"]},{"name":"ICMR-National Institute for Tribal Health Research, Jabalpur","place":["Madhya Pradesh, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"112721","DOI":"10.1016\/j.jim.2019.112721","article-title":"Standardized protocols for differentiation of THP-1 cells to macrophages with distinct M(IFN\u03b3+LPS), M(IL-4) and M(IL-10) phenotypes","volume":"478","author":"Baxter","year":"2020","journal-title":"J. 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