A Comprehensive Review of Natural Flavonoids with Anti-SARS-CoV-2 Activity.

The COVID-19 pandemic caused by SARS-CoV-2 has majorly impacted public health and economies worldwide. Although several effective vaccines and drugs are now used to prevent and treat COVID-19, natural products, especially flavonoids, showed great therapeutic potential early in the pandemic and thus attracted particular attention. Quercetin, baicalein, baicalin, EGCG (epigallocatechin gallate), and luteolin are among the most studied flavonoids in this field. Flavonoids can directly or indirectly exert antiviral activities, such as the inhibition of virus invasion and the replication and inhibition of viral proteases. In addition, flavonoids can modulate the levels of interferon and proinflammatory factors. We have reviewed the previously reported relevant literature researching the pharmacological anti-SARS-CoV-2 activity of flavonoids where structures, classifications, synthetic pathways, and pharmacological effects are summarized. There is no doubt that flavonoids have great potential in the treatment of COVID-19. However, most of the current research is still in the theoretical stage. More studies are recommended to evaluate the efficacy and safety of flavonoids against SARS-CoV-2.

Distribution, Biotransformation, Pharmacological Effects, Metabolic Mechanism and Safety Evaluation of Platycodin D: A Comprehensive Review.

Platycodonis Radix (Jiegeng), the dried root of Platycodon grandiflorum, is a traditional herb used as both medicine and food. Its clinical application for the treatment of cough, phlegm, sore throat, pulmonary and respiratory diseases has been thousands of years in China. Platycodin D is the main active ingredient in Platycodonis Radix, which belongs to the family of pentacyclic triterpenoid saponins because it contains an oleanolane type aglycone linked with double sugar chains. Modern pharmacology has demonstrated that Platycodin D displays various biological activities, such as analgesics, expectoration and cough suppression, promoting weight loss, anti-tumor and immune regulation, suggesting that Platycodin D has the potential to be a drug candidate and an interesting target as a natural product for clinical research. In this review, the distribution and biotransformation, pharmacological effects, metabolic mechanism and safety evaluation of Platycodin D are summarized to lay the foundation for further studies.

Prospects for the development of drugs with anti-viral activity based on licorice

The current situation with the widespread of a socially dangerous virus from the genus Coronavirus (SARS-CoV-2) and the announcement of a pandemic in connection with this demand the creation of new antiviral drugs since no specific treatment and prophylaxis against this disease has yet been found. Among medicinal plants that are widespread and exhibit multidirectional pharmacological activity, licorice should be noted. The active components contained in licorice, i.e. more than 20 triterpenoids and about 300 flavonoids coupled with glycyrrhizic acid (GL) referred to by the term "glycyrrhizin", have been widely studied for a long time. GL acts indirectly, interferes with the penetration of the virus into the cell, affects the components (HMGB1 protein) necessary for normal viral reproduction, and potentiates the production of interferon γ and α. GL acts against SARS-associated coronavirus infection by inducing the synthesis of nitric oxide synthase, which inhibits viral replication. However, GL may also be helpful in acute respiratory distress syndrome. The combination of the multidirectional pharmacological effects of GL and its derivatives make the licorice-containing preparations promising components of complex antiviral therapy. Currently, research into licorice-containing dosage forms continues from the perspective of creating vaginal suppositories with a thick extract of licorice. © 2021 Sami Publishing Company. All rights reserved.

Traditional Uses, Pharmacological Effects, and Molecular Mechanisms of Licorice in Potential Therapy of COVID-19.

The current Coronavirus disease 2019 (COVID-19) pandemic has become a global challenge, and although vaccines have been developed, it is expected that mild to moderate patients will control their symptoms, especially in developing countries. Licorice, not only a food additive, but also a common traditional Chinese herbal medicine, which has several pharmacological effects, such as anti-inflammation, detoxification, antibacterial, antitussive, and immunomodulatory effects, especially in respiratory diseases. Since the outbreak of COVID-19, glycyrrhizin, glycyrrhizin diamine and glycyrrhizin extract have been widely studied and used in COVID-19 clinical trials. Therefore, it is a very interesting topic to explore the material basis, pharmacological characteristics and molecular mechanism of licorice in adjuvant treatment of COVID-19. In this paper, the material basis of licorice for the prevention and treatment of COVID-19 is deeply analyzed, and there are significant differences among different components in different pharmacological mechanisms. Glycyrrhizin and glycyrrhetinic acid inhibit the synthesis of inflammatory factors and inflammatory mediators by blocking the binding of ACE 2 to virus spike protein, and exert antiviral and antibacterial effects. Immune cells are stimulated by multiple targets and pathways to interfere with the pathogenesis of COVID-19. Liquiritin can prevent and cure COVID-19 by simulating type I interferon. It is suggested that licorice can exert its therapeutic advantage through multi-components and multi-targets. To sum up, licorice has the potential to adjuvant prevent and treat COVID-19. It not only plays a significant role in anti-inflammation and anti-ACE-2, but also significantly improves the clinical symptoms of fever, dry cough and shortness of breath, suggesting that licorice is expected to be a candidate drug for adjuvant treatment of patients with early / mild COVID-19.

Pharmacological Effects of Selected Medicinal Plants and Vitamins Against COVID-19.

The coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It is a serious disease that has caused multiple deaths in various countries in the world. Globally, as of May 23, 2021, the total confirmed cases of COVID-19 have reach 166,346,635 with a total of 3,449,117 deaths. Several recent scientific studies have shown that medicinal plants and vitamins can benefit and improve the health of COVID-19 patients. However, the benefits of medicinal plants and vitamins in the treatment of COVID-19 remain unproven. Therefore, the objective of this article is to expounds the benefits of using medicinal plants (Allium sativum, curcumin, Nigella sativa, Zingiber officitale) and vitamins (vitamin C and vitamin D) that possess the antiviral properties for the prevention and/or control of COVID-19. To reach our objective, we searched scientific databases of ongoing trials in the Centers for Disease Control and Prevention websites, PubMed Central, Medline databases, and Google Scholar websites. We also searched databases on World Health Organization International Clinical Trials Registry Platform to collect relevant papers. We found that all of the selected medicinal plants and vitamins possess antiviral activities, and their individual intake shows promise for the prevention and/or control of COVID-19. We conclude that, the selected medicinal plants and vitamins possess anti-viral properties that are more likely to prevent and/or disrupt the SARS-CoV-2 replication cycle, enhance the human immune system and promote good health.

Potential beneficial role of probiotics on the outcome of COVID-19 patients: An evolving perspective.

BACKGROUND AND AIMS: Probiotics can support the body's systems in fighting viral infections. This review is aimed to focus current knowledge about the use of probiotics as adjuvant therapy for COVID-19 patients. METHODS: We performed an extensive research using the PubMed-LitCovid, Cochrane Library, Embase databases, and conducting manual searches on Google Scholar, Elsevier Connect, Web of Science about this issue. RESULTS: We have found several papers reporting data about the potential role of probiotics as well as contrasting experimental data about it. CONCLUSIONS: Most data show good results demonstrating that probiotics can play a significant role in fighting SARS-CoV-2 infection, also compared with their use in the past for various diseases. They seem effective in lowering inflammatory status, moreover in patients with chronic comorbidities such as cancer and diabetes, improving clinical outcomes.

Applications, phytochemistry, pharmacological effects, pharmacokinetics, toxicity of Scutellaria baicalensis Georgi. and its probably potential therapeutic effects on COVID-19: a review.

Scutellaria baicalensis Georgi. (SB) is a common heat-clearing medicine in traditional Chinese medicine (TCM). It has been used for thousands of years in China and its neighboring countries. Clinically, it is mostly used to treat diseases such as cold and cough. SB has different harvesting periods and processed products for different clinical symptoms. Botanical researches proved that SB included in the Chinese Pharmacopoeia (1st, 2020) was consistent with the medicinal SB described in ancient books. Modern phytochemical analysis had found that SB contains hundreds of active ingredients, of which flavonoids are its major components. These chemical components are the material basis for SB to exert pharmacological effects. Pharmacological studies had shown that SB has a wide range of pharmacological activities such as antiinflammatory, antibacterial, antiviral, anticancer, liver protection, etc. The active ingredients of SB were mostly distributed in liver and kidney, and couldn't be absorbed into brain via oral absorption. SB's toxicity was mostly manifested in liver fibrosis and allergic reactions, mainly caused by baicalin. The non-medicinal application prospects of SB were broad, such as antibacterial plastics, UV-resistant silk, animal feed, etc. In response to the Coronavirus Disease In 2019 (COVID-19), based on the network pharmacology research, SB's active ingredients may have potential therapeutic effects, such as baicalin and baicalein. Therefore, the exact therapeutic effects are still need to be determined in clinical trials. SB has been reviewed in the past 2 years, but the content of these articles were not comprehensive and accurate. In view of the above, we made a comprehensive overview of the research progress of SB, and expect to provide ideas for the follow-up study of SB.