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ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Virology
Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1540934
KAURENOIC ACID IS A POTENT INHIBITOR OF SARS-COV-2 RNA SYNTHESIS, VIRION ASSEMBLY AND RELEASE IN VITRO
Provisionally accepted
Igor de Andrade Santos1,2
Victória Riquena Grosche1,2,3
Natasha Marques Cassani1,2
Rodrigo Cassio Sola Veneziani4
Gustavo Lima Ribeiro4
Jairo Kenupp Bastos5Nilson Nicolau-Junior1
Andres Merits6
Carlos Henrique Gomes Martins1Mark Harris2*
Ana Carolina Gomes Jardim1,3*- 1Federal University of Uberlandia, Uberlândia, Minas Gerais, Brazil
- 2University of Leeds, Leeds, England, United Kingdom
- 3Institute of Biosciences, Humanities and Exact Sciences, São Paulo State University, Sao Jose do Rio Preto, Brazil
- 4Nucleus of Research in Sciences and Technology, University of Franca, Franca, Brazil
- 5Department of Pharmaceutical Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
- 6University of Tartu, Tartu, Tartu County, Estonia
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the Coronavirus Disease 2019 (COVID-19) pandemic, continues to pose global health challenges despite the existence of approved vaccines and antiviral drugs. The emergence of new variants of SARS-CoV-2 and lingering post-COVID complications necessitate continuous exploration for effective treatments. Kaurenoic acid (KA) is a tetracyclic diterpenoid isolated from plants of the Copaifera genus and was previously recognized for its anti-inflammatory, antibacterial, antifungal, and antitumor properties.However, there is a lack of knowledge in vitro encompassing KA effect on viruses. Here, we evaluated its effect on SARS-CoV-2 replication for the first time. 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 greater reduction of release of SARS-CoV-2 virions was observed. We suggest that KA interacts with SARS-CoV-2 proteases through molecular docking. In conclusion, KA emerges as an inhibitor of SARS-CoV-2 proteases and therefore, its replication cycle. It could be a good candidate for further investigation in clinical assays against SARS-CoV-2 infection.
Keywords: antiviral, COVID-19, natural compounds, SARS-CoV-2, Phytotherapeutics
Received: 06 Dec 2024; Accepted: 08 Apr 2025.
Copyright: © 2025 Santos, Grosche, Cassani, Veneziani, Ribeiro, Bastos, Nicolau-Junior, Merits, Martins, Harris and Jardim. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Mark Harris, University of Leeds, Leeds, LS2 9JT, England, United Kingdom
Ana Carolina Gomes Jardim, Federal University of Uberlandia, Uberlândia, 38408-100, Minas Gerais, Brazil
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.