Plants have been used for the prevention and treatment of diseases since the early days of humankind and constitute the natural sources of today's modern medicine. Approximately one-quarter of approved drugs are derived from plants. Plant steroids are a group of biologically active secondary metabolites with a 5𝛼 and 5𝛽 gonane carbon skeleton. There is immense chemical diversity in plant steroids due to the side chains, oxidation status of the carbons in the tetracyclic core, and methyl groups. Plant steroids are classified into several groups based on their biological functions and structures, also on their mechanism of biosynthesis. All subtypes have been investigated for their anti-cancer, immunomodulatory, anti-inflammatory, and anti-viral properties. The novel coronavirus disease (COVID-19) is caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), which carries an RNA genome. An intense effort has been made in terms of effective treatment strategies and vaccine development since it was declared a pandemic. Nucleoside analogs such as favipiravir and remdesivir are used to block RNA-dependent RNA polymerase enzymes. Other strategies including neuraminidase inhibitors, chloroquine, and hydroxychloroquine as immunomodulatory agents, stem cell and cytokine based therapies are being conducted. One part of the therapies against SARS-CoV-2 is focused on the spike (S) protein of the virus that binds to the host receptor, angiotensin-converting enzyme 2 (ACE2). It has been suggested that SARS-CoV-2 S protein has a free fatty acid-binding pocket, and according to molecular simulations, steroids are ligands that bind to this pocket. Therefore, this review summarizes the plant steroid biological actions as well as their anti-viral potential against SARS-CoV-2 infection.
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