Abstract
In late 2019, COVID-19 emerged in Wuhan, China. Currently, it is an ongoing global health threat stressing the need for therapeutic compounds. Linking the virus life cycle and its interaction with cell receptors and internal cellular machinery is key to developing therapies based on the control of infectivity and inflammation. In this framework, we evaluate the combination of cannabidiol (CBD), as an anti-inflammatory molecule, and terpenes, by their anti-microbiological properties, in reducing SARS-CoV-2 infectivity. Our group settled six formulations combining CBD and terpenes purified from Cannabis sativa L, Origanum vulgare, and Thymus mastichina. The formulations were analyzed by HPLC and GC-MS and evaluated for virucide and antiviral potential by in vitro studies in alveolar basal epithelial, colon, kidney, and keratinocyte human cell lines. Conclusions and Impact: We demonstrate the virucide effectiveness of CBD and terpene-based formulations. F2TC reduces the infectivity by 17%, 24%, and 99% for CaCo-2, HaCat, and A549, respectively, and F1TC by 43%, 37%, and 29% for Hek293T, HaCaT, and Caco-2, respectively. To the best of our knowledge, this is the first approach that tackles the combination of CBD with a specific group of terpenes against SARS-CoV-2 in different cell lines. The differential effectiveness of formulations according to the cell line can be relevant to understanding the pattern of virus infectivity and the host inflammation response, and lead to new therapeutic strategies.
| Original language | English |
|---|---|
| Article number | 841459 |
| Journal | Frontiers in Immunology |
| Volume | 13 |
| DOIs | |
| Publication status | Published - 15 Feb 2022 |
Bibliographical note
Publisher Copyright:Copyright © 2022 Santos, Barata, Charmier, Lehmann, Rodrigues, Melosini, Pais, Sousa, Teixeira, Santos, Rocha, Baylina and Fernandes.
Funding
This research was partially funded by the European Commission, European Regional Development, FEDER/02/SAICT/2020/ 072560 SI-B7-2020-15, POCI-01-02B7-FEDER-053456, BIOBLOCKCOVID. The funding allowed to perform the collection and harvesting of the medicinal plants, extract and purify the terpenes and formulations, execute the formulations, and execute preliminary assays related to toxicity. Considering in vitro virucide assays and gene expression assays, the work was partially funded by FCT – Fundação para a Ciência e Tecnologia (REF UID/BIM/04293/2019) and was partially supported by grants 104 and 112 of the 1st edition of RESEARCH4COVID (FCT) and by the grant 418 from the 2nd edition of RESEARCH4COVID-19 (FCT). This work was also partially supported by FEDER-European Regional Development Fund with the grant FEDER/02/SAICT/2020/072560. We would like to acknowledge the researchers that participated in the BioBlockCOVID project, especially Prof. Jo?o Ramalho Santos for providing the A549 and HaCaT cell lines and execution of preliminary cytotoxicity assays, Prof. Jos? Paulo Sousa, and Dr. Tiago Luz for the ecotoxicity assays, and Prof. Rui Ribeiro and Dra. Matilde Moreira Santos for the aquatic toxicity assays. We acknowledge the assistance in hydrodistillation to Prof. Ana Cristina Figueiredo, Faculdade de Ci?ncias da Universidade de Lisboa, CESAM Lisboa.
| Funders | Funder number |
|---|---|
| FCT - Fundação para a Ciência e a Tecnologia | RESEARCH4COVID-19, 104, 418, REF UID/BIM/04293/2019 |
| European Commission | |
| FCT - Fundação para a Ciência e a Tecnologia | |
| Universidade de Lisboa | |
| European Regional Development Fund | SI-B7-2020-15, FEDER/02/SAICT/2020/072560, POCI-01-02B7-FEDER-053456 |
Keywords
- CBD - cannabidiol
- SARS-CoV-2
- endocannabinoid system (ECS)
- essential oil (EO)
- formulations
- terpenes
- therapeutics
