{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T10:58:06Z","timestamp":1785495486305,"version":"3.56.0"},"reference-count":96,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"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. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This study aims to develop DABPU-DM derivatives that inhibit host adipose triglyceride lipase (ATGL) and identify the one with the highest broad-spectrum anti-coronaviral efficacy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The antiviral effectiveness of DABPU-DM derivatives against representative viruses from all four genera within the subfamily\n                      <jats:italic>Orthocoronavirinae<\/jats:italic>\n                      was assessed using western blot, RT-qPCR, and immunofluorescence assay (IFA). The reduction in free fatty acid (FFA) and free glycerol (FG) levels following ATGL inhibition was measured with FFA and FG quantification assays. The antiviral effect of DABPU-DE with remdesivir against SARS-CoV-2, either alone or in combination, was evaluated by IFA, and their synergistic effect was analyzed using SynergyFinder 3.0.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among six ATGL inhibitors, DABPU-DE exhibited the highest antiviral activity and safety, yielding a more favorable selectivity index than the other compounds. The enhanced antiviral effectiveness of DABPU-DE was linked to its diethylurea group, which increases ATGL binding affinity by enhancing hydrophobic and hydrogen-bonding interactions. In contrast, the weakest antiviral effect was observed with DABPU-DPh because its bulky diphenylurea group sterically hindered optimal binding and reduced interactions with ATGL. Additionally, combining DABPU-DE with remdesivir, which targets viral RNA-dependent RNA polymerase, produced strong, synergistic suppression of SARS-CoV-2 infection in Vero E6 cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings indicate that the broad-spectrum anti-coronaviral activity of these compounds, particularly DABPU-DE, provides a promising preclinical foundation. This study underscores the potential of ATGL-targeted interventions as a viable strategy for managing current SARS-CoV-2 variants and preparing for future coronavirus outbreaks.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1786048","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T04:43:49Z","timestamp":1785300229000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["DABPU-DE targeting host adipose triglyceride lipase provides broad-spectrum anti-coronavirus effects in vitro"],"prefix":"10.3389","volume":"17","author":[{"given":"Ragab","family":"Farouk","sequence":"first","affiliation":[{"name":"Host-Directed Antiviral Research Center, Chonnam National University","place":["Gwangju, Republic of Korea"]},{"name":"Department of Avian and Rabbit Medicine, Faculty of Veterinary Medicine, Assiut University","place":["Assiut, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Ju","family":"Lee","sequence":"additional","affiliation":[{"name":"Host-Directed Antiviral Research Center, Chonnam National University","place":["Gwangju, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaimaa","family":"Aboelmagd","sequence":"additional","affiliation":[{"name":"Host-Directed Antiviral Research Center, Chonnam National University","place":["Gwangju, Republic of Korea"]},{"name":"Department of Zoonoses, Faculty of Veterinary Medicine, Assiut University","place":["Assiut, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyung-Jun","family":"Kwon","sequence":"additional","affiliation":[{"name":"Host-Directed Antiviral Research Center, Chonnam National University","place":["Gwangju, Republic of Korea"]},{"name":"Functional Biomaterials Research Center, Korea Research Institute of Bioscience and Biotechnology","place":["Jeongeup-si, Jeollabuk-do, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seong-Hun","family":"Jeong","sequence":"additional","affiliation":[{"name":"Host-Directed Antiviral Research Center, Chonnam National University","place":["Gwangju, Republic of Korea"]},{"name":"Functional Biomaterials Research Center, Korea Research Institute of Bioscience and Biotechnology","place":["Jeongeup-si, Jeollabuk-do, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seok In","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Chonnam National University","place":["Gwangju, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dae-Eun","family":"Cheong","sequence":"additional","affiliation":[{"name":"Host-Directed Antiviral Research Center, Chonnam National University","place":["Gwangju, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sieknay","family":"Ny","sequence":"additional","affiliation":[{"name":"Host-Directed Antiviral Research Center, Chonnam National University","place":["Gwangju, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hae-Rang","family":"Seo","sequence":"additional","affiliation":[{"name":"Host-Directed Antiviral Research Center, Chonnam National University","place":["Gwangju, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changhee","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Gyeongsang National University","place":["Jinju, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunae","family":"Kim","sequence":"additional","affiliation":[{"name":"Host-Directed Antiviral Research Center, Chonnam National University","place":["Gwangju, Republic of Korea"]},{"name":"College of Pharmacy, Chosun University","place":["Gwangju, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunwoo","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Chonnam National University","place":["Gwangju, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoung-Oh","family":"Cho","sequence":"additional","affiliation":[{"name":"Host-Directed Antiviral Research Center, Chonnam National University","place":["Gwangju, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"002261","DOI":"10.1099\/jgv.0.002261","article-title":"Synergistic antiviral effect of host Adipose Triglyceride Lipase-directed DABPU-DE with coronavirus RNA-dependent RNA polymerase-targeting remdesivir on feline infectious peritonitis virus","volume":"107","author":"Aboelmagd","year":"2026","journal-title":"J. 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