Glycyrrhetinic acid for COVID-19

IntroductionTraditional Chinese medicine (TCM) pharmacies in Taiwan have been a vital healthcare resource in Chinese communities, with generations of accumulated TCM knowledge playing a crucial role in infectious disease prevention and treatment. However, as proprietors age and the industry declines, this valuable ethnomedicinal knowledge faces the risk of being lost. Therefore, documenting and analyzing the knowledge used by Taiwanese TCM pharmacies in combating COVID-19 is essential for the preservation and application of ethnomedicine.MethodsThis study employed a stratified sampling method to survey 106 TCM pharmacies in Taiwan, collecting 61 TCM formulae against COVID-19. The medicinal materials were compiled, and analysis were conducted using relative frequency of citation (RFC) and the Phi correlation coefficient to examine the relationships among TCMs. Furthermore, cluster analysis was applied to establish TCM combination patterns.ResultsThis study recorded a total of 70 medicinal materials and identified 30 commonly used ones, categorizing them into four major groups: Group A (heat-clearing and detoxifying): As similar as NRICM101, suitable for moderate to severe cases. Group B (heat-clearing and tonifying): Suitable for mild cases, with both antiviral and immune-boosting effects. Group C (symptom relief): Primarily used for relieving cough, expelling phlegm, and alleviating discomfort. Group D (tonifying and strengthening): Suitable for uninfected individuals to enhance immunity.DiscussionThis study successfully documented and analyzed the TCM usage patterns of Taiwanese TCM pharmacies in combating COVID-19, revealing their alignment with modern TCM theories. The findings not only contribute to the preservation of ethnobotanical knowledge but also serve as a reference for developing herbal prevention strategies and healthcare products, ensuring that traditional medical wisdom can play a greater role within the modern healthcare system.

<title>Abstract</title> <p>The continuous development of SARS-CoV-2 has given rise to the NB1.8.1 variant, which exhibits augmented pathogenicity, immune escape, and drug resistance against traditional therapeutics. The current study investigates a multi-layered systems pharmacology approach for identifying new therapeutic candidates that act on both viral entry and host-mediated inflammatory storms. By combining a seven-layer Intrinsic Network Pharmacology (INP) protocol with Network Pharmacology tools, we dissected the molecular failure network triggered by NB1.8.1, with emphasis on spike protein mutations that increase ACE2 binding, disrupt early interferon responses, and induce extreme cytokine and IgE storms. The HR1 and HR2 domain of the S2 fusion machinery was found to be a key weakness. We identified and confirmed a triterpenoid glycoside, ZINC000014930714, with high-affinity docking into the HR1 groove and strong pseudovirus fusion inhibition. Concurrently, we identified glycyrrhizin, a readily available natural saponin found in licorice, as a suitable surrogate with comparable fusion inhibition. Additional important modulators including camostat as an inhibitor of TMPRSS2, baricitinib targeting JAK and STAT signaling, sulforaphane as a Nrf2 activator, and metformin as an AMPK activator were incorporated into an inhalable nano-liposomal formulation strategy aimed at inhibiting viral propagation and resultant downstream immune storms. Network pharmacology modeling established that the indicated combination closes down several failure nodes in the INP layers. Our research offers a system-wide approach that not only reveals timely antiviral candidates against NB1.8.1 but also provides an adaptive platform for quick transition to emerging SARS-CoV-2 variants.</p>

The outbreak of SARS-CoV-2 developed into a global pandemic affecting millions of people worldwide. Despite one year of intensive research, the current treatment options for SARS-CoV-2 infected people are still limited. Clearly, novel antiviral compounds for the treatment of SARS-CoV-2 infected patients are still urgently needed. Complementary medicine is used along with standard medical treatment and accessible to a vast majority of people worldwide. Natural products with antiviral activity may contribute to improve the overall condition of SARS-CoV-2 infected individuals. In the present study, we investigated the antiviral activity of glycyrrhizin, the primary active ingredient of the licorice root, against SARS-CoV-2. We demonstrated that glycyrrhizin potently inhibits SARS-CoV-2 replication in vitro. Furthermore, we uncovered the underlying mechanism and showed that glycyrrhizin blocks the viral replication by inhibiting the viral main protease Mpro that is essential for viral replication. Our data indicate that the consumption of glycyrrhizin-containing products such as licorice root tea of black licorice may be of great benefit for SARS-CoV-2 infected people. Furthermore, glycyrrhizin is a good candidate for further investigation for clinical use to treat COVID-19 patients.

Background: In the last years, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused more than 760 million infections and 6.9 million deaths. Currently, remains a public health problem with limited pharmacological treatments. Among the virus drug targets, the SARS-CoV-2 spike protein attracts the development of new anti-SARS-CoV-2 agents. Objective: The aim of this work was to identify new compounds derived from natural products (BIOFACQUIM and Selleckchem databases) as potential inhibitors of the spike receptor binding domain (RBD)-ACE2 binding complex. Methods: Molecular docking, molecular dynamics simulations, and ADME-Tox analysis were performed to screen and select the potential inhibitors. ELISA-based enzyme assay was done to confirm our predictive model. Results: Twenty compounds were identified as potential binders of RBD of the spike protein. In vitro assay showed compound B-8 caused 48% inhibition at 50 μM, and their binding pattern exhibited interactions via hydrogen bonds with the key amino acid residues present on the RBD. Conclusion: Compound B-8 can be used as a scaffold to develop new and more efficient antiviral drugs.

The COVID-19 pandemic has had a significant and lasting impact on the world. Four years on, despite the existence of effective vaccines, the continuous emergence of new SARS-CoV-2 variants remains a challenge for long-term immunity. Additionally, there remain few purpose-built antivirals to protect individuals at risk of severe disease in the event of future coronavirus outbreaks. A promising mechanism of action for novel coronavirus antivirals is the inhibition of viral entry. To facilitate entry, the coronavirus spike glycoprotein interacts with angiotensin converting enzyme 2 (ACE2) on respiratory epithelial cells. Blocking this interaction and consequently viral replication may be an effective strategy for treating infection, however further research is needed to better characterize candidate molecules with antiviral activity before progressing to animal studies and clinical trials. In general, antiviral drugs are developed from purely synthetic compounds or synthetic derivatives of natural products such as plant secondary metabolites. While the former is often favored due to the higher specificity afforded by rational drug design, natural products offer several unique advantages that make them worthy of further study including diverse bioactivity and the ability to work synergistically with other drugs. Accordingly, there has recently been a renewed interest in natural product-derived antivirals in the wake of the COVID-19 pandemic. This review provides a summary of recent research into coronavirus entry inhibitors, with a focus on natural compounds derived from plants, honey, and marine sponges.

The emergence of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected many countries throughout the world. As urgency is a necessity, most efforts have focused on identifying small molecule drugs that can be repurposed for use as anti-SARS-CoV-2 agents. Although several drug candidates have been identified using in silico method and in vitro studies, most of these drugs require the support of in vivo data before they can be considered for clinical trials. Several drugs are considered promising therapeutic agents for COVID-19. In addition to the direct-acting antiviral drugs, supportive therapies including traditional Chinese medicine, immunotherapies, immunomodulators, and nutritional therapy could contribute a major role in treating COVID-19 patients. Some of these drugs have already been included in the treatment guidelines, recommendations, and standard operating procedures. In this article, we comprehensively review the approved and potential therapeutic drugs, immune cells-based therapies, immunomodulatory agents/drugs, herbs and plant metabolites, nutritional and dietary for COVID-19.

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had a profound impact on the world’s health and economy. Although the end of the pandemic may come in 2023, it is generally believed that the virus will not be completely eradicated. Most likely, the disease will become an endemicity. The rapid development of vaccines of different types (mRNA, subunit protein, inactivated virus, etc.) and some other antiviral drugs (Remdesivir, Olumiant, Paxlovid, etc.) has provided effectiveness in reducing COVID-19’s impact worldwide. However, the circulating SARS-CoV-2 virus has been constantly mutating with the emergence of multiple variants, which makes control of COVID-19 difficult. There is still a pressing need for developing more effective antiviral drugs to fight against the disease. Plants have provided a promising production platform for both bioactive chemical compounds (small molecules) and recombinant therapeutics (big molecules). Plants naturally produce a diverse range of bioactive compounds as secondary metabolites, such as alkaloids, terpenoids/terpenes and polyphenols, which are a rich source of countless antiviral compounds. Plants can also be genetically engineered to produce valuable recombinant therapeutics. This molecular farming in plants has an unprecedented opportunity for developing vaccines, antibodies, and other biologics for pandemic diseases because of its potential advantages, such as low cost, safety, and high production volume. This review summarizes the latest advancements in plant-derived drugs used to combat COVID-19 and discusses the prospects and challenges of the plant-based production platform for antiviral agents.