{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T18:34:36Z","timestamp":1791657276732,"version":"4.3.4"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T00:00:00Z","timestamp":1754956800000},"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>The continuous evolution of coronaviruses poses persistent and severe threats to both human and animal health. While \u03b1- and \u03b2-coronaviruses mainly infect mammals, including humans, \u03b3-coronaviruses predominantly infect poultry, causing substantial economic losses. Their rapid mutation rates and wide host tropism underscore the urgent demand for pan-coronavirus therapeutics. Here, we systematically investigated the antiviral potency and mechanism of action of PB28, a selective sigma-1 receptor antagonist, across \u03b1-, \u03b2-, and \u03b3-coronaviruses. Molecular docking predicted a stable interaction between PB28 and the sigma-1 receptor. PB28 exhibits robust <jats:italic>in vitro<\/jats:italic> antiviral activity, effectively inhibiting the replication of \u03b2-coronaviruses (SARS-CoV-2 and its Beta, Delta, and Omicron variants; HCoV-OC43), \u03b1-coronaviruses (PEDV and TGEV), and \u03b3-coronaviruses (IBV). Broad-spectrum antiviral efficacy is further validated by viral titration assays. <jats:italic>In vivo<\/jats:italic>, PB28 administration in K18-hACE2 mice infected with SARS-CoV-2 Delta and BALB\/c mice infected with HCoV-OC43 led to significantly reduced viral loads, attenuated multi-organ pathology, and improved survival and body weight maintenance. In parallel, PB28 treatment in IBV-infected chicken embryos and neonatal chicks enhanced survival, supported embryogenesis, and alleviated tissue damage. Collectively, PB28 demonstrates cross-genus antiviral efficacy, likely mediated through modulation of the sigma-1 receptor. These findings highlight PB28 as a promising lead compound for the development of pan-coronavirus therapeutics.<\/jats:p>","DOI":"10.3389\/fmicb.2025.1636035","type":"journal-article","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T05:31:30Z","timestamp":1754976690000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Broad-spectrum antiviral activity of the sigma-1 receptor antagonist PB28 against coronaviruses"],"prefix":"10.3389","volume":"16","author":[{"given":"Gaojie","family":"Song","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingling","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingpeng","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dapeng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Shang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuiling","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junwei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,12]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"589810","DOI":"10.3389\/fphar.2020.589810","article-title":"PB28, the Sigma-1 and Sigma-2 receptors modulator with potent anti-SARS-CoV-2 activity: a review about its pharmacological properties and structure affinity relationships","volume":"11","author":"Abate","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"12798","DOI":"10.1038\/s41598-023-39662-w","article-title":"A conformational rearrangement of the SARS-CoV-2 host protein sigma-1 is required for antiviral activity: insights from a combined in-silico\/in-vitro approach","volume":"13","author":"Abatematteo","year":"2023","journal-title":"Sci. Rep."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"705575","DOI":"10.3389\/fphys.2021.705575","article-title":"Sigmar1's molecular, cellular, and biological functions in regulating cellular pathophysiology","volume":"12","author":"Aishwarya","year":"2021","journal-title":"Front. 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Infect."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2025.1636035\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T05:31:31Z","timestamp":1754976691000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2025.1636035\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,12]]},"references-count":34,"alternative-id":["10.3389\/fmicb.2025.1636035"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2025.1636035","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,12]]},"article-number":"1636035"}}