{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T05:25:38Z","timestamp":1767677138415,"version":"3.48.0"},"reference-count":42,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,3]],"date-time":"2026-01-03T00:00:00Z","timestamp":1767398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Regional Joint Fund of the National Natural Science Foundation of China","award":["U24A20366"],"award-info":[{"award-number":["U24A20366"]}]},{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"crossref","award":["2023YFF1304900"],"award-info":[{"award-number":["2023YFF1304900"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20202002"],"award-info":[{"award-number":["BK20202002"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Frontiers Medical Center, Tianfu Jincheng Laboratory","award":["TFJC2023010007"],"award-info":[{"award-number":["TFJC2023010007"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Transient receptor potential vanilloid 1 (TRPV1) channels are critical mediators of cutaneous allergic inflammation, contributing to pruritus, erythema, and hypersensitivity in allergic skin disorders. Despite their therapeutic potential, clinically available TRPV1 inhibitors remain limited, leaving effective treatment options lacking. Here, we focused on a self-constructed virtual pentapeptide library and identified a highly selective TRPV1 inhibitor that demonstrated pronounced anti-allergic effects in human skin assays. Through structure-based virtual screening of approximately 200,000 peptide conformations, five candidate pentapeptides, especially P5 (DQKNC), exhibited the inhibition. Electrophysiological recordings showed that P5 inhibited TRPV1 currents with nanomolar potency, while exhibiting negligible effects on major cardiac and neuronal ion channels, highlighting its favorable selectivity and safety profile. In capsaicin-induced human skin hypersensitivity tests, topical P5 significantly reduced burning pain, erythema, and pruritus, with simultaneous application providing the most robust relief. These findings reveal a short peptide with strong TRPV1 selectivity and demonstrable efficacy in alleviating skin inflammation and allergic responses, supporting the notion that rationally designed pentapeptides may represent promising topical therapeutics for allergic skin disorders.<\/jats:p>","DOI":"10.3390\/cells15010079","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T15:28:57Z","timestamp":1767626937000},"page":"79","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Virtual Screening\u2013Guided Discovery of a Selective TRPV1 Pentapeptide Inhibitor with Topical Anti-Allergic Efficacy"],"prefix":"10.3390","volume":"15","author":[{"given":"Lulu","family":"Liu","sequence":"first","affiliation":[{"name":"The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, Peptide and Small Molecule Drug R&D Platform of Furong Laboratory, College of Life Sciences, Hunan Normal University, Changsha 410081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenqian","family":"Hou","sequence":"additional","affiliation":[{"name":"The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, Peptide and Small Molecule Drug R&D Platform of Furong Laboratory, College of Life Sciences, Hunan Normal University, Changsha 410081, China"},{"name":"Suixian Public Inspection and Testing Center, Suizhou 441300, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qinyi","family":"He","sequence":"additional","affiliation":[{"name":"The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, Peptide and Small Molecule Drug R&D Platform of Furong Laboratory, College of Life Sciences, Hunan Normal University, Changsha 410081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fuchu","family":"Yuan","sequence":"additional","affiliation":[{"name":"The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, Peptide and Small Molecule Drug R&D Platform of Furong Laboratory, College of Life Sciences, Hunan Normal University, Changsha 410081, China"},{"name":"Frontiers Medical Center, Tianfu Jincheng Laboratory, Chengdu 610212, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changrun","family":"Guo","sequence":"additional","affiliation":[{"name":"School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruxia","family":"Liu","sequence":"additional","affiliation":[{"name":"The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, Peptide and Small Molecule Drug R&D Platform of Furong Laboratory, College of Life Sciences, Hunan Normal University, Changsha 410081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Biao","family":"Huang","sequence":"additional","affiliation":[{"name":"The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, Peptide and Small Molecule Drug R&D Platform of Furong Laboratory, College of Life Sciences, Hunan Normal University, Changsha 410081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atikan","family":"Wubulikasimu","sequence":"additional","affiliation":[{"name":"The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, Peptide and Small Molecule Drug R&D Platform of Furong Laboratory, College of Life Sciences, Hunan Normal University, Changsha 410081, China"},{"name":"Frontiers Medical Center, Tianfu Jincheng Laboratory, Chengdu 610212, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingqiang","family":"Rong","sequence":"additional","affiliation":[{"name":"The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, Peptide and Small Molecule Drug R&D Platform of Furong Laboratory, College of Life Sciences, Hunan Normal University, Changsha 410081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s12967-019-02200-2","article-title":"The capsaicin receptor TRPV1 is the first line defense protecting from acute non damaging heat: A translational approach","volume":"18","author":"Rosenberger","year":"2020","journal-title":"J. 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