{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T17:02:46Z","timestamp":1793638966552,"version":"4.5.1"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T00:00:00Z","timestamp":1746748800000},"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:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for the coronavirus disease 2019 (COVID-19) pandemic, continues to pose global health challenges despite the availability of approved vaccines and antiviral drugs. The emergence of new variants of SARS-CoV-2 and ongoing post-COVID complications necessitate continuous exploration of effective treatments. Kaurenoic acid (KA) is a tetracyclic diterpenoid isolated from plants of the\n                      <jats:italic>Copaifera<\/jats:italic>\n                      genus and has been previously recognized for its anti-inflammatory, antibacterial, antifungal, and antitumor properties. However, there is a lack of knowledge about the\n                      <jats:italic>in vitro<\/jats:italic>\n                      effects of KA on viruses. Here, we evaluated its effect on SARS-CoV-2 replication for the first time.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p>KA demonstrated a high selective index of 16.1 against SARS-CoV-2 and robust effectiveness against the B.1.617.2 (Delta) and BA.2 (Omicron) variants. Mechanistically, KA was shown to impair the post-entry steps of viral replication. In a subgenomic replicon system, we observed a decrease in viral RNA synthesis in different cell lines. Using an infectious virus, a larger reduction in the release of SARS-CoV-2 virions was observed. We suggest that KA interacts with SARS-CoV-2 proteases through molecular docking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In conclusion, KA emerges as an inhibitor of SARS-CoV-2 proteases and, consequently, its replication cycle. It could be a good candidate for further investigation in clinical assays against SARS-CoV-2 infection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2025.1540934","type":"journal-article","created":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T01:29:54Z","timestamp":1746754194000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Kaurenoic acid is a potent inhibitor of SARS-CoV-2 RNA synthesis, virion assembly, and release in vitro"],"prefix":"10.3389","volume":"16","author":[{"given":"Igor Andrade","family":"Santos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria Riquena","family":"Grosche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha Marques","family":"Cassani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo C\u00e1ssio Sola","family":"Veneziani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo Lima","family":"Ribeiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jairo Kenupp","family":"Bastos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilson","family":"Nicolau-Junior","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andres","family":"Merits","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Henrique Gomes","family":"Martins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Harris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Carolina Gomes","family":"Jardim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,9]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1016\/S2213-2600(22)00528-8","article-title":"Effects of remdesivir in patients hospitalised with COVID-19: a systematic review and individual patient data meta-analysis of randomised controlled trials","volume":"11","author":"Amstutz","year":"2023","journal-title":"Lancet Respir. 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