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We evaluated the effects of the ACEi enalapril (ENA) and the ARB losartan (LOS) on SARS-CoV-2 infection in human ex vivo-cultured, precision-cut lung slices (PCLS) obtained from normal human lung tissue.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>PCLS were pre-treated for 5d with vehicle, LOS or ENA (300 \u00b5M), followed by mock infection or infection with SARS-CoV-2 and incubation with vehicle, LOS or ENA for 1d or 2d. Thereafter, PCLS were harvested for analysis of viral replication, inflammatory responses, endoplasmic reticulum (ER) stress and apoptosis pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Both LOS and ENA significantly reduced viral replication in PCLS, with ENA being more potent. LOS was more efficient than ENA in reducing the expression of\n                      <jats:italic>IL1B<\/jats:italic>\n                      ,\n                      <jats:italic>CCL2<\/jats:italic>\n                      ,\n                      <jats:italic>CXCL2<\/jats:italic>\n                      and\n                      <jats:italic>TNFA<\/jats:italic>\n                      , but not of\n                      <jats:italic>IL6<\/jats:italic>\n                      , whereas ENA preferentially caused a reduction of\n                      <jats:italic>IL6<\/jats:italic>\n                      and\n                      <jats:italic>CCL2<\/jats:italic>\n                      in SARS-CoV-2-infected PCLS. Further, ENA, but not LOS, significantly decreased the expression of viral entry factors, ACE2 and transmembrane serine protease 2 (TMPRSS2), in infected PCLS. Importantly, LOS or ENA did not exert cytotoxic effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>RAAS-antagonizing drugs do not seem to exert detrimental effects during SARS-CoV-2 infection. In opposite, in an ex-vivo model of human PCLS, such treatment was found to dampen SARS-CoV-2 infection and consecutive inflammation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12931-025-03463-8","type":"journal-article","created":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T08:25:49Z","timestamp":1768292749000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["RAAS antagonists dampen the SARS-CoV-2 infection in ex-vivo cultured human precision-cut lung slices"],"prefix":"10.1186","volume":"27","author":[{"given":"Poornima","family":"Mahavadi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Korfei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christin","family":"M\u00fcller-Ruttloff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clemens","family":"Ruppert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ekaterina","family":"Krauss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Dorfm\u00fcller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Gattenloehner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefanie","family":"Dimmeler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elie","family":"El Agha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saverio","family":"Bellusci","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanne","family":"Herold","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Biruta","family":"Witte","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Ziebuhr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Guenther","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,1,13]]},"reference":[{"key":"3463_CR1","doi-asserted-by":"publisher","first-page":"2052","DOI":"10.1001\/jama.2020.6775","volume":"323","author":"S Richardson","year":"2020","unstructured":"Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T, Davidson KW, the Northwell C-RC, Barnaby DP, Becker LB, Chelico JD, et al. 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Informed consent was obtained and the study protocol was approved by the Ethics Committee of the Justus Liebig University Giessen (No. 111\/08 and 58\/15).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"28"}}