Phyto-pharmacological perspective of Silymarin: A potential prophylactic or therapeutic agent for COVID-19, based on its promising immunomodulatory, anti-coagulant and anti-viral property

Abstract

Coronavirus disease 2019 (COVID-19) triggered by a new viral pathogen, named severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2), is now a global health emergency. This debilitating viral pandemic not only paralyzed the normal daily life of the global community but also spread rapidly via global travel. To date there are no effective vaccines or specific treatments against this highly contagious virus; therefore, there is an urgent need to advocate novel prophylactic or therapeutic interventions for COVID-19. This brief opinion critically discusses the potential of Silymarin, a flavonolignan with diverse pharmacological activity having antiinflammatory, antioxidant, antiplatelet, and antiviral properties, with versatile immune-cytokine regulatory functions, that able to bind with transmembrane protease serine 2 (TMPRSS2) and induce endogenous antiviral cytokine interferon-stimulated gene 15, for the management of COVID-19. Silymarin inhibits the expression of host cell surface receptor TMPRSS2 with a docking binding energy corresponding to -1,350.61 kcal/mol and a full fitness score of -8.11. The binding affinity of silymarin with an impressive virtual score exhibits significant potential to interfere with SARS-CoV-2 replication. We propose in-depth pre-clinical and clinical review studies of silymarin for the development of anti-COVID-19 lead, based on its clinical manifestations of COVID-19 and multifaceted bioactivities.

Keywords: ACE2; COVID-19; ISG15; SARS-COV-2; Silymarin; TMPRSS2; anticoagulant; immunomodulatory; pro-inflammatory-cytokine.

FIGURE 1

The structures of the different bioactive molecules of flavonolignans derivatives derived from the silymarin

FIGURE 2

Multi‐facets of silymarin action. Established and probable pharmacological roles of silymarin have been depicted. A “+” indicates a stimulatory effect, whereas a “−” an inhibitory role. A down arrow indicates a reduction in expression levels. The red dash sign indicates steps where silymarin could stop a particular step in SARS‐CoV‐2 pathogenesis. Details are in the text [Colour figure can be viewed at wileyonlinelibrary.com]