SilCOVID19: Silibinin milk thistle extract investigated as a therapeutic option against SARS-CoV-2

Milk thistle (Silybum marianum) is a herbaceous plant that’s usually adorned with a purple-pink flower. Milk thistle seed extracts have validated benefits for liver health. They also have been used both preventively and curatively to protect the liver from toxins, including alcohol, aspirin, acetaminophen, heavy metals and the death cap mushroom. The active constituent of milk thistle seeds (fruits) is a flavonoid called silymarin, the key component of which is silibinin. Recent investigation suggests that it may have further benefits that go beyond liver support. For instance, silibinin has a recognized antitumor activity, and could also be effective in the fight against COVID-19. This is the conclusion of a study by the Catalan Institute of Oncology (ICO) and the Girona Biomedical Research Institute (IDIBGI), recently published in the Journal of Clinical Medicine, presenting the reasons for an evaluation of its possible use as a treatment for the coronavirus SARS-CoV-2 2019, which is causing a global pandemic with hundreds of thousands of infections and deaths worldwide.

Function of silibinin against COVID-19

According to this study, the clinical-molecular evidence of silibinin as a possible treatment for COVID-19 is presented in three parts:

As an immunodulator of the “cytokine storm”: it analyzes the ability of silibinin to act as an immunomodulator of the so-called “cytokine storm”, one of the key mechanisms in the poor prognosis of patients COVID-19 with acute respiratory distress syndrome. This mechanism would depend on the STAT3 protein, a molecular target of silibinin that the same researchers had already described in patients with brain metastases. Thus, this first level of action would take place in the “host / patient” area.

As an antiviral: it is also presented, for the first time, a comprehensive computational analysis of a new mechanism of silibinin against RNA polymerase of SARS-CoV-2, the main component of the virus replication / transcription machinery. This computational study, developed in collaboration with Dr. José Antonio Encinar (University of Elche), predicts a pharmacological behavior of silibinin very similar to that known with Remdesivir, which has recently been the first drug approved by the European Agency for Drug (EMA) against COVID-19. This second level of action would take place in the virus itself.

This dual nature of silibinin, capable of acting both in the systemic environment via STAT3 – controlling the exacerbated and uncontrolled response of the immune system against lung epithelial cells damaged by infection – and in the virus by directly blocking RNA polymerase from SARS-CoV-2, provides a good reason for the development of clinical studies.