Kaurenoic acid is a potent inhibitor of SARS-CoV-2 RNA synthesis, virion assembly, and release in vitro
IntroductionSevere 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...
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2025.1540934/full |
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| author | Igor Andrade Santos Igor Andrade Santos Victoria Riquena Grosche Victoria Riquena Grosche Victoria Riquena Grosche Natasha Marques Cassani Natasha Marques Cassani Rodrigo Cássio Sola Veneziani Gustavo Lima Ribeiro Jairo Kenupp Bastos Nilson Nicolau-Junior Andres Merits Carlos Henrique Gomes Martins Mark Harris Ana Carolina Gomes Jardim Ana Carolina Gomes Jardim |
| author_facet | Igor Andrade Santos Igor Andrade Santos Victoria Riquena Grosche Victoria Riquena Grosche Victoria Riquena Grosche Natasha Marques Cassani Natasha Marques Cassani Rodrigo Cássio Sola Veneziani Gustavo Lima Ribeiro Jairo Kenupp Bastos Nilson Nicolau-Junior Andres Merits Carlos Henrique Gomes Martins Mark Harris Ana Carolina Gomes Jardim Ana Carolina Gomes Jardim |
| author_sort | Igor Andrade Santos |
| collection | DOAJ |
| description | IntroductionSevere 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 Copaifera genus and has been previously recognized for its anti-inflammatory, antibacterial, antifungal, and antitumor properties. However, there is a lack of knowledge about the in vitro effects of KA on viruses. Here, we evaluated its effect on SARS-CoV-2 replication for the first time.Methods and ResultsKA 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.ConclusionIn 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. |
| format | Article |
| id | doaj-art-111ad3122b7240acbcd4387128f12bbc |
| institution | OA Journals |
| issn | 1664-302X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj-art-111ad3122b7240acbcd4387128f12bbc2025-08-20T02:28:16ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2025-05-011610.3389/fmicb.2025.15409341540934Kaurenoic acid is a potent inhibitor of SARS-CoV-2 RNA synthesis, virion assembly, and release in vitroIgor Andrade Santos0Igor Andrade Santos1Victoria Riquena Grosche2Victoria Riquena Grosche3Victoria Riquena Grosche4Natasha Marques Cassani5Natasha Marques Cassani6Rodrigo Cássio Sola Veneziani7Gustavo Lima Ribeiro8Jairo Kenupp Bastos9Nilson Nicolau-Junior10Andres Merits11Carlos Henrique Gomes Martins12Mark Harris13Ana Carolina Gomes Jardim14Ana Carolina Gomes Jardim15Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, BrazilFaculty of Biological Sciences, School of Molecular and Cellular Biology, University of Leeds, Leeds, United KingdomInstitute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, BrazilFaculty of Biological Sciences, School of Molecular and Cellular Biology, University of Leeds, Leeds, United KingdomInstitute of Biosciences, Humanities and Exact Sciences, São Paulo State University, São Jose do Rio Preto, BrazilInstitute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, BrazilFaculty of Biological Sciences, School of Molecular and Cellular Biology, University of Leeds, Leeds, United KingdomNucleus of Research in Sciences and Technology, University of Franca, Franca, BrazilNucleus of Research in Sciences and Technology, University of Franca, Franca, BrazilFaculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, BrazilInstitute of Biotechnology, Federal University of Uberlândia (UFU), Uberlândia, BrazilInstitute of Bioengineering, University of Tartu, Tartu, EstoniaInstitute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, BrazilFaculty of Biological Sciences, School of Molecular and Cellular Biology, University of Leeds, Leeds, United KingdomInstitute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, BrazilFaculty of Biological Sciences, School of Molecular and Cellular Biology, University of Leeds, Leeds, United KingdomIntroductionSevere 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 Copaifera genus and has been previously recognized for its anti-inflammatory, antibacterial, antifungal, and antitumor properties. However, there is a lack of knowledge about the in vitro effects of KA on viruses. Here, we evaluated its effect on SARS-CoV-2 replication for the first time.Methods and ResultsKA 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.ConclusionIn 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.https://www.frontiersin.org/articles/10.3389/fmicb.2025.1540934/fullantiviralCOVID-19natural compoundsSARS-CoV-2phytotherapeutics |
| spellingShingle | Igor Andrade Santos Igor Andrade Santos Victoria Riquena Grosche Victoria Riquena Grosche Victoria Riquena Grosche Natasha Marques Cassani Natasha Marques Cassani Rodrigo Cássio Sola Veneziani Gustavo Lima Ribeiro Jairo Kenupp Bastos Nilson Nicolau-Junior Andres Merits Carlos Henrique Gomes Martins Mark Harris Ana Carolina Gomes Jardim Ana Carolina Gomes Jardim Kaurenoic acid is a potent inhibitor of SARS-CoV-2 RNA synthesis, virion assembly, and release in vitro Frontiers in Microbiology antiviral COVID-19 natural compounds SARS-CoV-2 phytotherapeutics |
| title | Kaurenoic acid is a potent inhibitor of SARS-CoV-2 RNA synthesis, virion assembly, and release in vitro |
| title_full | Kaurenoic acid is a potent inhibitor of SARS-CoV-2 RNA synthesis, virion assembly, and release in vitro |
| title_fullStr | Kaurenoic acid is a potent inhibitor of SARS-CoV-2 RNA synthesis, virion assembly, and release in vitro |
| title_full_unstemmed | Kaurenoic acid is a potent inhibitor of SARS-CoV-2 RNA synthesis, virion assembly, and release in vitro |
| title_short | Kaurenoic acid is a potent inhibitor of SARS-CoV-2 RNA synthesis, virion assembly, and release in vitro |
| title_sort | kaurenoic acid is a potent inhibitor of sars cov 2 rna synthesis virion assembly and release in vitro |
| topic | antiviral COVID-19 natural compounds SARS-CoV-2 phytotherapeutics |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2025.1540934/full |
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