Authors	Theme of the study and the main findings of the authors
Sikander M, et al., 2020 [41]	Bibliographic review in the context of the SARS-COV-2 pandemic, with analysis of antivirals, immunomodulators and hepatoprotective nutraceuticals. Identification of damage to hepatocytes caused by the SARS-COV-19 viral infection and by the drugs used for this disease.
Palit P, et al., 2021 [45]	Proposition of new drug targets, Furin and Transmembrane protease serine 2, based on their pathophysiological implication on SARS-COV-2 infection. It is reported that the Spike glycoprotein of CoV-2 harbors a Furin cleavage site which is activated by the host cell enzyme to make the virus more susceptible to its primary receptor, angiotensin-converting enzyme-2. Use of nano-suspension based intra-nasal or oral nebulizer spray, containing a complex of phytocomponents, to treat mild to moderate SARS-COV-2 infection.
Wang W, et al., 2021 [47]	Comparison of Traditional Chinese Medicine and Western Allopathic Medicine. The evaluation of therapeutic approaches in China, during the pandemic, demonstrated the use of antiviral drugs, human immunoglobulins, corticosteroids, and intestinal microbiological regulators aimed at virus infection or immunomodulation.
Wang W, et al., 2020 [46]	Comparative study in patients with severe COVID-19 in Wuhan, analyzing 43 male patients aged 57-70 years and the use of traditional Chinese medicine (TCM). TMC granules, combined with usual care, showed no improvement beyond usual care alone. However, the use of TMC granules reduced the 28-day mortality rate and the time to fever alleviation. Nevertheless, CHM granules may be associated with high risk of fibrinolysis.
Palit P, et al., 2021 [32]	Evaluation of selected antiviral phytopharmaceuticals capable of binding to specific targets for the management of COVID-19. Inhibition against Chikungunya, Mayaro, and influenza A viruses. The binding affinity of silymarin with an impressive virtual score exhibits significant potential to interfere with SARS-COV-2 replication.
Liu et al., 2019 [24]	Development of highly bioavailable silybinin nanoparticles and evaluation of efficiency against HCV infection. Treatment efficiently restricted HCV cell-to-cell transmission, suggesting that they retained silybinin’s robust anti-HCV activity. Oral administration of SB-NP in rodents produced no apparent in vivo toxicity, in addition its efficiently reduced HCV infection of primary human hepatocytes.
Anand AV, et al., 2021 [26]	Verification of the action of herbal compounds, with confirmation of antiviral effects through inhibition of viral replication, lipid metabolism, apoptosis, protein, and cytokine expression; lignins may have potent anti-SARS-COV-2 actions, as they have also shown effects against SARS-COV-2.
Sardanelli AM, et al., 2021 [69]	Search for molecules whose biochemical and toxicological profile was known that could be the starting point for the development of antiviral therapies. The results-obtained in silico and in vitro-prove that silybin and silymarin are useful as a therapeutic strategy against COVID-19.
Fakhri S, et al. 2020 [60]	Survey of several mechanisms of action related to herbal compounds, including silymarin and rutin. Presentation of mechanisms of infection and diffusion of SARS CoV-2.
Majnooni MB, et al 2020 [66]	Comprehensive review of SARS-COV-2 mechanisms of action and presentation of herbal medicines with antiviral and anti-inflammatory potential for the airways. Phytochemical compounds showed prominent and significant anti-inflammatory effects in reducing lung damage caused by SARS-COV-2 severe acute respiratory syndrome.
Kumar S, et al 2021 [71]	Demonstrate the binding of phytochemicals such as sarsasapogenin, ursonic acid, curcumin, ajmalicin, novobiocin, silymarin and aranotin, piperine, gingerol, rosmarinic acid and alpha terpinyl acetate to the viral protein Nsp15, relevant to the inhibition of SARS-COV-2 replication. Demonstration of the high binding energy of silymarin and rutin and hydrogen bonds. Analysis and design of drugs based on the results and interaction with the Nsp15 protein.
Palit, Mukhopadhyay, Chattopadhyay, 2021. [32]	Discussion of the potential of Silymarin for the management of COVID-19. Silymarin inhibits expression of the host cell surface receptor TMPRSS2. Silymarin’s binding affinity with an impressive virtual score exhibits significant potential to interfere with SARS-COV-2 replication.
Speciale A, et al., 2021 [70]	Exploring silybinin’s in situ ability to interact with key SARS-COV-2 target proteins and in vitro effects against cytokine-induced inflammation and dysfunction in human umbilical vein endothelial cells (HUVECs). Silybinin forms a stable complex with the SARS-COV-2 RBD spike protein, has good negative binding affinity with Mpro, and interacts with many residues in the active site of Mpro, thus supporting its potentiality in inhibiting viral entry and replication. Pre-treatment of HUVECs with silybinin reduced TNF-α-induced gene expression of the pro-inflammatory genes IL-6 and MCP-1, as well as of PAI-1, a critical factor in coagulopathy and thrombosis, and of ET-1, a peptide involved in hemostatic vasoconstriction.