{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T06:16:31Z","timestamp":1792131391013,"version":"4.4.0"},"reference-count":27,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T00:00:00Z","timestamp":1677456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordination for the Improvement of Higher Education Personnel (CAPES)","doi-asserted-by":"publisher","award":["88881.171440\/2018-01"],"award-info":[{"award-number":["88881.171440\/2018-01"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The SARS-CoV-2 pandemic highlighted the need for broad-spectrum antivirals to increase our preparedness. Patients often require treatment by the time that blocking virus replication is less effective. Therefore, therapy should not only aim to inhibit the virus, but also to suppress pathogenic host responses, e.g., leading to microvascular changes and pulmonary damage. Clinical studies have previously linked SARS-CoV-2 infection to pathogenic intussusceptive angiogenesis in the lungs, involving the upregulation of angiogenic factors such as ANGPTL4. The \u03b2-blocker propranolol is used to suppress aberrant ANGPTL4 expression in the treatment of hemangiomas. Therefore, we investigated the effect of propranolol on SARS-CoV-2 infection and the expression of ANGPTL4. SARS-CoV-2 upregulated ANGPTL4 in endothelial and other cells, which could be suppressed with R-propranolol. The compound also inhibited the replication of SARS-CoV-2 in Vero-E6 cells and reduced the viral load by up to ~2 logs in various cell lines and primary human airway epithelial cultures. R-propranolol was as effective as S-propranolol but lacks the latter\u2019s undesired \u03b2-blocker activity. R-propranolol also inhibited SARS-CoV and MERS-CoV. It inhibited a post-entry step of the replication cycle, likely via host factors. The broad-spectrum antiviral effect and suppression of factors involved in pathogenic angiogenesis make R-propranolol an interesting molecule to further explore for the treatment of coronavirus infections.<\/jats:p>","DOI":"10.3390\/ijms24054588","type":"journal-article","created":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T03:29:48Z","timestamp":1677468588000},"page":"4588","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["R-Propranolol Has Broad-Spectrum Anti-Coronavirus Activity and Suppresses Factors Involved in Pathogenic Angiogenesis"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5590-4918","authenticated-orcid":false,"given":"Melissa","family":"Thaler","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2244-7992","authenticated-orcid":false,"given":"Clarisse","family":"Salgado-Benvindo","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anouk","family":"Leijs","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Tas","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis K.","family":"Ninaber","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6798-6383","authenticated-orcid":false,"given":"Jack L.","family":"Arbiser","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Emory University School of Medicine, Atlanta, GA 30322, USA"},{"name":"Division of Dermatology, Veterans Affairs Medical Center, Decatur, GA 30033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3297-2309","authenticated-orcid":false,"given":"Eric J.","family":"Snijder","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2617-9243","authenticated-orcid":false,"given":"Martijn J.","family":"van Hemert","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/s00428-021-03053-1","article-title":"The pulmonary pathology of COVID-19","volume":"478","author":"Matter","year":"2021","journal-title":"Virchows Arch. 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