{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T12:52:09Z","timestamp":1790772729959,"version":"4.1.0"},"reference-count":40,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,23]],"date-time":"2022-01-23T00:00:00Z","timestamp":1642896000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Taif University Researchers Supporting Project, Taif University, Taif, Saudi Arabia","award":["TURSP2020\/296"],"award-info":[{"award-number":["TURSP2020\/296"]}]},{"name":"\u2018Hundreds of Talents Program\u2019, Guangzhou University China","award":["28099201-302"],"award-info":[{"award-number":["28099201-302"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Gastric cancer is the fifth most frequent cancer and the third major cause of mortality worldwide. Helicobacter pylori, a bacterial infection linked with GC, injects the cytotoxin-associated antigen A (CagA; an oncoprotein) into host cells. When the phosphorylated CagA protein enters the cell, it attaches to other cellular components, interfering with normal cellular signaling pathways. CagA plays an important role in the progression of GC by interacting with phosphatidylserine of the host cell membrane. Therefore, disrupting the CagA\u2013phosphatidylserine connection using small molecules appears to be a promising therapeutic approach. In this report, we screened the natural compounds from ZINC database against the CagA protein using the bioinformatics tools. Hits were initially chosen based on their physicochemical, absorption, distribution, metabolism, excretion, and toxicity (ADMET) characteristics, as well as other drug-like characteristics. To locate safe and effective hits, the PAINS filter, binding affinities estimation, and interaction analysis were used. Three compounds with high binding affinity and specificity for the CagA binding pocket were discovered. The final hits, ZINC153731, ZINC69482055, and ZINC164387, were found to bind strongly with CagA protein, with binding energies of \u221211.53, \u221210.67, and \u22129.21 kcal\/mol, respectively, which were higher than that of the control compound (\u22127.25 kcal\/mol). Further, based on binding affinity and interaction pattern, two leads (ZINC153731, ZINC69482055) were chosen for molecular dynamics (MD) simulation analysis. MD results showed that they displayed stability in their vicinity at 100 ns. This study suggested that these compounds could be used as possible inhibitors of CagA protein in the fight against GC. However, additional benchwork tests are required to validate them as CagA protein inhibitors.<\/jats:p>","DOI":"10.3390\/molecules27030732","type":"journal-article","created":{"date-parts":[[2022,1,23]],"date-time":"2022-01-23T20:34:40Z","timestamp":1642970080000},"page":"732","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Targeting Cytotoxin-Associated Antigen A, a Virulent Factor of Helicobacter pylori-Associated Gastric Cancer: Structure-Based In Silico Screening of Natural Compounds"],"prefix":"10.3390","volume":"27","author":[{"given":"Shan","family":"He","sequence":"first","affiliation":[{"name":"School of Chemistry and Chemical Engineering, Guangzhou University, Guangzhou 510006, China"},{"name":"Institute for Nano Scale Science and Technology, College of Science and Engineering, Flinders University, Bedford Park, SA 5042, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulraheem Ali","family":"Almalki","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7219-9149","authenticated-orcid":false,"given":"Misbahuddin M.","family":"Rafeeq","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, King Abduaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziaullah M.","family":"Sain","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, King Abduaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8348-9451","authenticated-orcid":false,"given":"Amany I.","family":"Alqosaibi","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9277-3996","authenticated-orcid":false,"given":"Mashael M.","family":"Alnamshan","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6910-0534","authenticated-orcid":false,"given":"Ibtesam S.","family":"Al-Dhuayan","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7680-8423","authenticated-orcid":false,"given":"Abdul","family":"Rahaman","sequence":"additional","affiliation":[{"name":"School of Food Science and Engineering, South China University of Technology, Guangzhou 510641, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Chemistry and Chemical Engineering, Guangzhou University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2841-5438","authenticated-orcid":false,"given":"Hamsa Jameel","family":"Banjer","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farah","family":"Anjum","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2857-3065","authenticated-orcid":false,"given":"Haitham Ali M.","family":"Alzghaibi","sequence":"additional","affiliation":[{"name":"Department of Health Informatics, College of Public Health and Health Informatics, Qassim University, Al Bukayriyah 52741, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali H.","family":"Alharbi","sequence":"additional","affiliation":[{"name":"Department of Health Informatics, College of Public Health and Health Informatics, Qassim University, Al Bukayriyah 52741, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5525-708X","authenticated-orcid":false,"given":"Qazi Mohammad Sajid","family":"Jamal","sequence":"additional","affiliation":[{"name":"Department of Health Informatics, College of Public Health and Health Informatics, Qassim University, Al Bukayriyah 52741, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,23]]},"reference":[{"key":"ref_1","first-page":"26","article-title":"Epidemiology of gastric cancer: Global trends, risk factors and prevention","volume":"14","author":"Rawla","year":"2019","journal-title":"Prz. 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