A Review of the Antiviral Activities of Glycyrrhizic Acid, Glycyrrhetinic Acid and Glycyrrhetinic Acid Monoglucuronide.

Licorice, a natural medicine derived from the roots and rhizomes of Glycyrrhiza species, possesses a wide range of therapeutic applications, including antiviral properties. Glycyrrhizic acid (GL) and glycyrrhetinic acid (GA) are the most important active ingredients in licorice. Glycyrrhetinic acid 3-O-mono-ß-d-glucuronide (GAMG) is the active metabolite of GL. GL and its metabolites have a wide range of antiviral activities against viruses, such as, the hepatitis virus, herpes virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and so on. Although their antiviral activity has been widely reported, the specific mechanism of action involving multiple links such as the virus itself, cells, and immunity are not clearly established. In this review, we will give an update on the role of GL and its metabolites as antiviral agents, and detail relevant evidence on the potential use and mechanisms of actions. Analyzing antivirals, their signaling, and the impacts of tissue and autoimmune protection may provide promising new therapeutic strategies.

The Interaction of the Transmembrane Domain of SARS-CoV-2 E-Protein with Glycyrrhizic Acid in Lipid Bilayer.

The interaction of the transmembrane domain of SARS-CoV-2 E-protein with glycyrrhizic acid in a model lipid bilayer (small isotropic bicelles) is demonstrated using various NMR techniques. Glycyrrhizic acid (GA) is the main active component of licorice root, and it shows antiviral activity against various enveloped viruses, including coronavirus. It is suggested that GA can influence the stage of fusion between the viral particle and the host cell by incorporating into the membrane. Using NMR spectroscopy, it was shown that the GA molecule penetrates into the lipid bilayer in a protonated state, but localizes on the bilayer surface in a deprotonated state. The transmembrane domain of SARS-CoV-2 E-protein facilitates deeper GA penetration into the hydrophobic region of bicelles at both acidic and neutral pH and promotes the self-association of GA at neutral pH. Phenylalanine residues of the E-protein interact with GA molecules inside the lipid bilayer at neutral pH. Furthermore, GA influences the mobility of the transmembrane domain of SARS-CoV-2 E-protein in the bilayer. These data provide deeper insight into the molecular mechanism of antiviral activity of glycyrrhizic acid.

Evaluation of the Antiviral Efficacy of Subcutaneous Nafamostat Formulated with Glycyrrhizic Acid against SARS-CoV-2 in a Murine Model.

The ongoing COVID-19 pandemic highlights the urgent need for effective antiviral agents and vaccines. Drug repositioning, which involves modifying existing drugs, offers a promising approach for expediting the development of novel therapeutics. In this study, we developed a new drug, MDB-MDB-601a-NM, by modifying the existing drug nafamostat (NM) with the incorporation of glycyrrhizic acid (GA). We assessed the pharmacokinetic profiles of MDB-601a-NM and nafamostat in Sprague-Dawley rats, revealing rapid clearance of nafamostat and sustained drug concentration of MDB-601a-NM after subcutaneous administration. Single-dose toxicity studies showed potential toxicity and persistent swelling at the injection site with high-dose administration of MDB-601a-NM. Furthermore, we evaluated the efficacy of MDB-601a-NM in protecting against SARS-CoV-2 infection using the K18 hACE-2 transgenic mouse model. Mice treated with 60 mg/kg and 100 mg/kg of MDB-601a-NM exhibited improved protectivity in terms of weight loss and survival rates compared to the nafamostat-treated group. Histopathological analysis revealed dose-dependent improvements in histopathological changes and enhanced inhibitory efficacy in MDB-601a-NM-treated groups. Notably, no viral replication was detected in the brain tissue when mice were treated with 60 mg/kg and 100 mg/kg of MDB-601a-NM. Our developed MDB-601a-NM, a modified Nafamostat with glycyrrhizic acid, shows improved protectivity against SARS-CoV-2 infection. Its sustained drug concentration after subcutaneous administration and dose-dependent improvements makes it a promising therapeutic option.

Jing Si Herbal Drink as a prospective adjunctive therapy for COVID-19 treatment: Molecular evidence and mechanisms

Background: SARS-CoV-2 has led to a sharp increase in the number of hospitalizations and deaths from pneumonia and multiorgan disease worldwide;therefore, SARS-CoV-2 has become a global health problem. Supportive therapies remain the mainstay treatments against COVID-19, such as oxygen inhalation, antiviral drugs, and antibiotics. Traditional Chinese medicine (TCM) has been shown clinically to relieve the symptoms of COVID-19 infection, and TCMs can affect the pathogenesis of SARS-CoV-2 infection in vitro. Jing Si Herbal Drink (JSHD), an eight herb formula jointly developed by Tzu Chi University and Tzu Chi Hospital, has shown potential as an adjuvant treatment for COVID-19 infection. A randomized controlled trial (RCT) of JSHD as an adjuvant treatment in patients with COVID-19 infection is underway Objectives: This article aims to explore the efficacy of the herbs in JSHD against COVID-19 infection from a mechanistic standpoint and provide a reference for the rational utilization of JSHD in the treatment of COVID-19. Method(s): We compiled evidence of the herbs in JSHD to treat COVID-19 in vivo and in vitro. Result(s): We described the efficacy and mechanism of action of the active ingredients in JSHD to treat COVID-19 based on experimental evidence. JSHD includes 5 antiviral herbs, 7 antioxidant herbs, and 7 anti-inflammatory herbs. In addition, 2 herbs inhibit the overactive immune system, 1 herb reduces cell apoptosis, and 1 herb possesses antithrombotic ability. Conclusion(s): Although experimental data have confirmed that the ingredients in JSHD are effective against COVID-19, more rigorously designed studies are required to confirm the efficacy and safety of JSHD as a COVID-19 treatment.Copyright © 2021

Anti-COVID-19 Traditional Chinese Medicine Database

Background: Novel coronavirus pneumonia COVID-19 has become a serious threat to human health. Traditional Chinese Medicine (TCM) has a good clinical effect in the treatment of COVID-19, with a high effective rate and a low rate of turning to the serious stage. Objective(s): We generated the web-accessed anti-COVID-19 TCM database to provide the anti-COVID-19 TCM information to develop effective drugs for the treatment of COVID-19. Method(s): Herein, we collected these prescriptions data by querying the CNKI and Wanfang Chinese da-tabases, the clinical guidance for COVID-19 pneumonia diagnosis and treatment, and further set up the web-accessible anti-COVID-19 TCM database. Result(s): Altogether, 293 different prescriptions are applied in four different COVID-19 stages of treat-ment, and the prevention of COVID-19 is composed of 452 TCM components. Conclusion(s): The database provides comprehensive information for anti-COVID TCM and thus would help to investigate novel ways to develop new anti-COVID-19 agents.Copyright © 2022 Bentham Science Publishers.

CLINICAL AND LABORATORY CHARACTERISTICS OF PATIENTS WITH LIVER DAMAGE IN THE COVID-19 EARLY REHABILITATION PERIOD

The emergence of COVID-19 has set health professionals tasks related to the rapid diagnosis and provision of medical care to patients. Patients with COVID-19 also have extrapulmonary symptoms;including clinical signs of damage to the gastrointestinal tract (GI tract) and the hepatobiliary system which are diagnosed in 26–53% of patients. Aim. The aim of the study was to evaluate clinical and laboratory indicators of liver damage in patients in the early rehabilitation period of COVID-19. Material and methods. There were 243 patients with COVID-19 aged 18–60 years under observation. The criteria for inclusion in the study were: transferred no earlier than 10 days before inclusion in the study COVID-19;at the time of inclusion in the study PCR-negative COVID-19. The indicators of the general blood test, in the blood serum – C-reactive protein, alanine aminotransferase, aspartate aminotransferase, gamma glutamyl aminotransferase, lactate dehydrogenase, alkaline phosphatase, total and direct bilirubin, albumin. Results and discussion. The assessment of the clinical condition of patients showed that the prevalence of respiratory syndrome was 81,48%, dyspeptic – 67,90%, hemorheological – 54,73%, asthenic – 42,39%, encephalopathy – 36,21%. In the general blood test, the hemoglobin level, the number of erythrocytes and platelets were significantly lower than in the control group (p<0,001, p<0,05 and p<0,001). The activity of blood enzymes in post COVID-19 patients included in the study was significantly increased compared to the control group: alanine aminotransferase exceeded the average values in the control group by almost 10 times, aspartate aminotransferase – almost 3 times, lactate dehydrogenase – 3 times, gamma glutamyl aminotransferase and alkaline phosphatase – almost one and a half times. The level of bilirubin b significantly exceeded the indicator recorded in the control group (p<0,001). The concentration of albumin in the peripheral blood of patients was reduced (p<0,001 the significance of the difference with the control group). Conclusion. In patients with liver damage in post COVID-19 patients the early rehabilitation period, the most frequent clinical syndromes were respiratory (81,48%) and dyspeptic (67,90%). Laboratory changes characteristic of hypochromic anemia, consumption thrombocytopenia, mesenchymal-inflammatory activity, liver functional disorders (the presence of cytolytic cholestatic syndromes and a decrease in protein synthesizing liver function) were also revealed. © 2018 the Author (s). Published by Kurdistan University of Medical Sciences.

CLINICAL AND LABORATORY CHARACTERISTICS OF PATIENTS WITH LIVER DAMAGE IN THE COVID-19 EARLY REHABILITATION PERIOD

The emergence of COVID-19 has set health professionals tasks related to the rapid diagnosis and provision of medical care to patients. Patients with COVID-19 also have extrapulmonary symptoms;including clinical signs of damage to the gastrointestinal tract (GI tract) and the hepatobiliary system which are diagnosed in 26–53% of patients. Aim. The aim of the study was to evaluate clinical and laboratory indicators of liver damage in patients in the early rehabilitation period of COVID-19. Material and methods. There were 243 patients with COVID-19 aged 18–60 years under observation. The criteria for inclusion in the study were: transferred no earlier than 10 days before inclusion in the study COVID-19;at the time of inclusion in the study PCR-negative COVID-19. The indicators of the general blood test, in the blood serum – C-reactive protein, alanine aminotransferase, aspartate aminotransferase, gamma glutamyl aminotransferase, lactate dehydrogenase, alkaline phosphatase, total and direct bilirubin, albumin. Results and discussion. The assessment of the clinical condition of patients showed that the prevalence of respiratory syndrome was 81,48%, dyspeptic – 67,90%, hemorheological – 54,73%, asthenic – 42,39%, encephalopathy – 36,21%. In the general blood test, the hemoglobin level, the number of erythrocytes and platelets were significantly lower than in the control group (p<0,001, p<0,05 and p<0,001). The activity of blood enzymes in post COVID-19 patients included in the study was significantly increased compared to the control group: alanine aminotransferase exceeded the average values in the control group by almost 10 times, aspartate aminotransferase – almost 3 times, lactate dehydrogenase – 3 times, gamma glutamyl aminotransferase and alkaline phosphatase – almost one and a half times. The level of bilirubin b significantly exceeded the indicator recorded in the control group (p<0,001). The concentration of albumin in the peripheral blood of patients was reduced (p<0,001 the significance of the difference with the control group). Conclusion. In patients with liver damage in post COVID-19 patients the early rehabilitation period, the most frequent clinical syndromes were respiratory (81,48%) and dyspeptic (67,90%). Laboratory changes characteristic of hypochromic anemia, consumption thrombocytopenia, mesenchymal-inflammatory activity, liver functional disorders (the presence of cytolytic cholestatic syndromes and a decrease in protein synthesizing liver function) were also revealed. © 2018 the Author (s). Published by Kurdistan University of Medical Sciences.

THE EFFECT OF HEPATOPROTECTORS ON THE STATE OF THE LIVER IN POST COVID-19 PATIENTS

Introduction. In previous studies, it was found that MERS-CoV and SARS-CoV cause damage to parenchymal organs, including liver damage in patients with COVID-19. Virus-induced influence on hepatocytes and cholangiocytes is considered one of the possible factors of liver failure. Direct viral damage to the liver can be detected in the infectious period, inflammatory and toxic damage can develop both in the acute period and in the post-infectious phase against the background of the rehabilitation period. Aim. The aim of the study was to study the effect of various hepatoprotectors on the functional state of the liver in patients in the early rehabilitation period of COVID-19. Material and methods. 243 post COVID-19 patients were under observation, depending on the therapy, the patients were divided into 4 groups: group 0 – group (n=60) – therapy without hepatoprotectors;ursodeoxycholic acid group (n=61) – ursodeoxycholic acid was included in therapy;glycyrrhizic acid and phospholipids group (n=63) – glycyrrhizic acid and phospholipids in the form of Phosphogliv tablets are included in therapy;group ademeteonin (n=59) – ademeteonin is included in therapy. The control examination was carried out a month later. The control group consisted of 20 healthy individuals. To assess the functional state of the liver in the blood of patients, the enzymes alanine aminotransferase, aspartate aminotransferase, gamma-glutamylaminotransferase, lactate dehydrogenase, alkaline phosphatase, total and direct bilirubin, albumin was determined. Conclusion. In patients in the early rehabilitation period of COVID-19, there are increase in the levels of enzymes alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, alkaline phosphatase and bilirubin in the blood, which indicates functional liver disorders. The use of hepatoprotectors makes it possible to increase the positive effect of rehabilitation on the severity of markers of cytolytic and cholestatic syndromes. Ursodeoxycholic acid has the most pronounced effect on normalization of alanine aminotransferase, total and direct bilirubin levels. © 2022, LLC "IMC" Modern Clinical Medicine. All rights reserved.

Efficacy and safety of glycyrrhizic acid preparation treating comorbid liver injury in COVID-19: A systematic review.

Background: No specific drug for COVID-19 has been found, and many studies have found that different degrees of liver injury often occurred after infection with COVID-19. Glycyrrhizic acid preparation (GAP) has been frequently used clinically, often combined with conventional treatments such as antiviral therapy, to improve the prognosis of COVID-19 and patients' liver function. Aims: To critically review and analyze clinical evidence on the efficacy and safety of GAP in the treatment of COVID-19 alone and COVID-19 with comorbid liver injury. Methods: A systematic literature review was performed following a sensitive searching strategy that examines all articles published in "WHO COVID-19 Research Database," "Cochrane Library," "VIP," "CNKI," "Wanfang," and "CBM" from 2020 to July 2022. Articles were evaluated by peer reviewers and used Joanna Briggs Institute (JBI) critical appraisal tools to complete the assessment of the risk of bias. Results: Ten clinical studies were finally included, involving 598 patients with COVID-19, of whom 189 were confirmed to be with comorbid liver injury. The main GAPs used are diammonium glycyrrhizinate and magnesium isoglycyrrhizinate, which have shown efficacy in improving liver function, inhibiting inflammation, and enhancing immunity. We are still seeking more related research. Conclusion: Glycyrrhizic acid preparations (mainly diammonium glycyrrhizinate and magnesium isoglycyrrhizinate) have a considerable clinical effect on improving liver function in patients with COVID-19 alone or with comorbid liver injury. Further studies on the use of GAP in the treatment of COVID-19 with comorbid liver injury and its mechanism are still needed. Systematic Review Registration: [www.crd.york.ac.uk/prospero], identifier [CRD42021234647].

Screening potential Q-Marker from Huoxiang Zhengqi Shui based on UPLC-Q-TOF-MS fingerprints and molecular docking

Objective To screen the potential quality markers (Q-Marker) of anti-coronavirus of Huoxiang Zhengqi Shui (, HZS) based on the ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF-MS) fingerprints and molecular docking. Methods UPLC-Q-TOF-MS fingerprints and chemometric methods were employed to establish fingerprints and find out the difference between the peaks for the 27 batches of HZS samples. The SARS-CoV-2 main protease (Mpro) inhibition potential of the differential compounds among the 27 batches of HZS were further predicted by molecular docking with remdesivir as positive control. Results The UPLC-Q-TOF-MS fingerprints of 27 batches of HZS samples were set up with 27 common peaks. Combined with hierarchical clustering analysis (HCA) and principal component analysis (PCA), 14 common peaks were determined as differential compounds, and nine of them were identified as hesperidin, oxypeucedanin, neobyakangelicol, sinensetin, glycyrrhizic acid, 3,5,6,7,8,3',4'-heptamethoxyflavone, tangeretin, imperatorin and phellopterin. Molecular docking results showed that a total of six differential compounds were proven to have a certain inhibitory effect on SARS-CoV-2 Mpro, which can be used as potential Q-Marker of HZS, including hesperidin, oxypeucedanin, neobyakangelicol, glycyrrhizic acid, imperatorin and phellopterin. Conclusion The potential Q-Marker of HZS was determined by UPLC-Q-TOF-MS fingerprints, chemometric analysis and molecular docking. This method may provide a certain reference for the identification of various drug components, analysis of the differences of the same type drug components and pharmaceutical activity evaluation. Copyright © 2022 Editorial Office of Chinese Traditional and Herbal Drugs. All rights reserved.

Antiviral Potential of Medicinal Plants for the COVID-19

Background: SARS-CoV-2 infection has spread throughout the globe and has become a terrible epidemic. Researchers all around the globe are working to understand the characteristics of coronavirus and are trying to find antiviral compounds as an alternative to vaccines. Objective(s): The present study has been conceptualized to screen the various metabolites of traditional therapeutic plants that can have crucial antiviral activity against COVID-19. Method(s): Medicinal plants are rich sources of therapeutic agents of human origin. In this study, active metabolites from plants such as O. sanctum, C. longa, A. indica, Z. officinale, A. paniculata, G. glabra, A. sativum, P. guajava, V. negundo and S. aromaticum have been studied. This study aims to control COVID-19, either by interfering with the Cysteine-like protease (3CLpro) component of COVID-19 or by blocking viral entry via the human angiotensin-converting enzyme 2 (ACE 2) receptor. The molecular docking of forty plant metabolites was studied with the 3Clpro component and ACE 2 receptors. In addition to this, the binding capacity of these two targets was also compared with hydroxychloroquine used for its treatment. Result(s): The results reveal that Glycyrrhizin binds to 3CLpro in a highly stable manner with the lowest binding energy. Glabridin, beta-sitosterol, beta-Caryophyllene, alpha-Curcumene, and Apigenin, among others, have shown effective interactions with both ACE 2 and 3CLpro. The study reveals the ability of more than 20 plant-based compounds against the COVID-19 infection cycle, which are more effective than hydroxychloroquine. Conclusion(s): Medicinal plant-based therapeutic compounds might provide quickly, sensitive, precise, and cost-effective alternative therapies. To reduce adverse effects, many pharmacological characteristics of medicinal plant agents should be adjusted. Copyright © 2022 Bentham Science Publishers.

Targeting spike protein-induced TLR/NET axis by COVID-19 therapeutic NRICM102 ameliorates pulmonary embolism and fibrosis.

The global COVID-19 pandemic remains a critical public health threat, as existing vaccines and drugs appear insufficient to halt the rapid transmission. During an outbreak from May to August 2021 in Taiwan, patients with severe COVID-19 were administered NRICM102, which was a traditional Chinese medicine (TCM) formula developed based on its predecessor NRICM101 approved for treating mild cases. This study aimed to explore the mechanism of NRICM102 in ameliorating severe COVID-19-related embolic and fibrotic pulmonary injury. NRICM102 was found to disrupt spike protein/ACE2 interaction, 3CL protease activity, reduce activation of neutrophils, monocytes and expression of cytokines (TNF-α, IL-1ß, IL-6, IL-8), chemokines (MCP-1, MIP-1, RANTES) and proinflammatory receptor (TLR4). NRICM102 also inhibited the spread of virus and progression to embolic and fibrotic pulmonary injury through reducing prothrombotic (vWF, PAI-1, NET) and fibrotic (c-Kit, SCF) factors, and reducing alveolar type I (AT1) and type II (AT2) cell apoptosis. NRICM102 may exhibit its protective capability via regulation of TLRs, JAK/STAT, PI3K/AKT, and NET signaling pathways. The study demonstrates the ability of NRICM102 to ameliorate severe COVID-19-related embolic and fibrotic pulmonary injury in vitro and in vivo and elucidates the underlying mechanisms.

Coronavirus infection and psoriasis: relationship and consequences

As numerous scientific data show, despite the fact that patients with severe psoriasis have a high risk of coronavirus infection, COVID-19 in this group proceeds quite easily. However, many specialists have encountered an unusual exacerbation of the pso-riatic process already after the infection, the reasons for which may be several. On the one hand, the skin is one of the target organs for SARS-CoV-2, on the other hand, exacerbations may be caused by the immune system response to the infection. The influence of specific therapy on the course of the psoriatic process is also not excluded. But interleukin status of patients with psoriasis is of the greatest interest. It is known that interleukin-6 (IL-6) plays an active role in pathogenesis of COVID-19 and cytokine storm arising at infection. It is also regarded as an indicator of inflammatory activity in psoriasis. In addition, IL-6 is involved in lipid and hepatobiliary disorders in this group of patients. It is also associated with IL-17, the role of which has been well studied in psoriasis and autoimmune hepatitis. Patients with psoriasis often have changes in biochemical blood parameters, similar to those seen with COVID-19. Combinations of all these factors can lead to exacerbation of psoriasis with predominance of erythroderma and toxic component. In our opinion, in such cases it is necessary to include in the therapy a systemic hepato-protective drug containing glycyrrhizic acid. It has a pronounced anti-inflammatory effect, inhibits IL-6 production and allows to achieve significant improvement of psoriatic process in a short time. © 2022, Remedium Group Ltd. All rights reserved.

Clinical value of diammonium glycyrrhizinate in treatment of COVID-19

To determine the clinical value of diammonium glycyrrhizinate (DG) in treatment of patients with novel coronavirus pneumonia (NCP). According to the random-number method, 104 NCP patients were divided equally into control group and observation group in our hospital. In the control group, patients were treated according to the Pneumonia diagnosis and treatment scheme for new coronavirus infection (trial version 5). In the observation group, patients were administered DG enteric capsules (150 mg, t.d.s.). All patients were treated continuously for 2 weeks. The clinical effects in both groups were observed. Levels of inflammation indicators [C-reactive protein (CRP), interleukin (IL) -4, tumor necrosis factor (TNF) -a] and immune-function indicators [cluster of differentiation (CD)3+, CD4+, CD8+, CD4+/CD8+] were compared between the two groups. Adverse reactions were documented. The prevalence of cure [19.23% (10/52) vs. 7.69% (4/ 52)], significant efficacy [28.85% (15/52) vs. 17.31% (9/52)] and total efficacy [61.54% (32/52) vs. 40.38% (20/52)] of the observation group was significantly higher than that of the control group (P < 0.05 for all). After treatment, the serum levels of CRP [(1.90 +or- 085) vs. (3.26 +or- 1.63) mg/L], IL-4 [(21.35 +or- 8.90) vs. (26.24 +or- 9.16) pg/mL], and TNF-a [(4.85 +or- 2.15) vs. (7.97 +or- 3.36) pg/mL] of the observation group were significantly lower than those of the control group (P < 0.05 for all). The levels of CD3+ [(6630 +or- 8.83)% vs. (54.19 +or- 7.79)%], CD4+ [(39.42 +or- 4.72)% vs, (33.18 +or- 4.10)%], CD8+ [(28.14 +or- 4.22)% vs. (23.39 +or- 3.88)%], and CD4+/CD8+ [(1.62+or- 043) vs. (1.21 +or- 0.29)] of the observation group were significantly higher than those of the control group (P < 0.05 for all). The prevalence of adverse reactions [15.38% (8/52) vs. 28.85% (15/52)] of the observation group was significantly lower than that of the control group (P < 0.05). DG has a significant clinical effect and a good safety profile for NCP treatment.

Synthesis, Antiviral, and Antibacterial Activity of the Glycyrrhizic Acid and Glycyrrhetinic Acid Derivatives.

Glycyrrhizic acid and its primary metabolite glycyrrhetinic acid, are the main active ingredients in the licorice roots (glycyrrhiza species), which are widely used in several countries of the world, especially in east asian countries (China, Japan). These ingredients and their derivatives play an important role in treating many diseases, especially infectious diseases such as COVID-19 and hepatic infections. This review aims to summarize the different ways of synthesising the amide derivatives of glycyrrhizic acid and the main ways to synthesize the glycyrrhitinic acid derivatives. Also, to determine the main biological and pharmacological activity for these compounds from the previous studies to provide essential data to researchers for future studies. Supplementary Information: The online version contains supplementary material available at 10.1134/S1068162022050132.

Management of COVID-19-A Review

Coronavirus disease-2019 (COVID-19) has gained much popularity not only in the Wuhan city of China but internationally also;in January 2020, the corona rapidly spread to many countries like the USA, Italy, Russia, India, Singapore, Pakistan, Thailand, Canada, Australia, England, and so on through passengers traveling to other countries. Corona patients can be cured with synthetic drugs, traditional herbal medicines (THM), use of Vitamin D and the quarantine approach. Different allopathic medicines, herbal extracts, and vitamin D have been observed to be useful in the treatment of novel coronavirus, like Remdesivir, hydroxychloroquine, Teicoplanin, Lopinavir+ Ritonavir, Ribavirin + corticosteroids, Glycyrrhizin, Sanguisorbae radix, Acanthopanacis cortex, Sophorae radix, etc. Various antiviral drugs are used to treat COVID-19, alone or in combination with other medications like Interferon-α, Lopinavir + Ritonavir, Arbidol, corticosteroids, etc., and some herbal extracts;also quarantine approach and Vitamin D are used that not only cure the infection but also boost up our immunity. For this review article, different papers were searched on Google Scholar, Scopus, WHO’s website, PubMed, clinicaltrials.gov and other relevant scientific research websites. In this review article, we have discussed the current strategies that are being used to treat COVID-19. Along with allopathic drugs, some herbal extracts can also be used to treat this novel coronavirus, like Glycyrrhizin, Sanguisorbae radix, Acanthopanacis cortex, Sophorae radix, etc. and even vitamin D.

Ayurveda and Siddha systems polyherbal formulations to treat COVID-19 caused by SARS-CoV-2 and brief insight on application of Molecular Docking and SWISS Target prediction tools to study efficacy of active molecules

Ayurveda and Siddha systems are the two ancient medical systems originated in India more than 4000 years ago had given many formulary and treatment methods against influenza like infections. Kabasura churan from Siddha system and Maha sudharshan churan from the Ayurvedic system are the two major formulations along with many other individual herbs mentioned in the texts to treat Influenza like infections. Kabasura churan and Maha Sudarshan churan both have antipyretic, analgesic and anti-inflammatory effects. Both formulations were prepared according to Siddha and Ayurvedic texts. Herbs mentioned in both formulations like Turmeric, Tulsi (Basil), Kalmegh (Andrographis), Black Pepper, Liquorice (Mulethi), and Dronapushpi (Leucas) etc., had direct antiviral effect. Herbs like Aswagandha, Ginger, Guduchi (Tinospora), Kulanjan (Galangal) etc., had immunomodulatory and anti-inflammatory effect. Active compounds from different herbs were selected to study their antiviral activity through molecular docking algorithm. Application of modern of tools like Bioinformatics and Highthroughput screening methods can predict the efficacy of the ancient documented formulations and can be compared as per their literature. Compounds like curcumin, Glycyrrhizin, Ursolic acid, Quercetin, Andrographolide, Coumarins etc. were showed polyspecific activity like inhibition of Spike protein, Furin, Main Protease (Mpro) and Papain like Proteases (PLpro). Thus we propose use of Kabasura churan and Maha Sudharshan churan as alternative complementary medicine as a palliative treatment against COVID-19 caused by SARS-CoV-2 by conducting proper Randomized Clinical Trials.

Ayurvedic antiviral agents: Overview of medicinal plants perspective

In recent years, it has been reported that many herbal plants contain antiviral agents which combat a human disease that is caused by pathogenic viruses. The natural products which are obtained from plants as antiviral agents against viruses have gone through researches to check the efficacy and potentials of the herbal products in the prevention of viral disorders. On the basis of randomized controlled studies and in-vivo studies, and in-vitro studies, some agents are utilized all across the globe. Progressively numerous studies on therapy of antivirals have been increased. Though, efficacy remains disputable for antiviral drugs that are employed for viral disorders. The viral diseases are challenging for the health of people around the world cause significant increase in mortality and enhance crises. There are many synthetic antiviral drugs that have a large number of side effects and have narrow therapeutic window range, while in the other hand herbal formulations have minimized side effects. The advantages of herbal formulation over synthetic drugs encourage us to devise and expand new herbal moieties against the emerging viral infections. The medicinal plants contain phytochemicals that have antiviral properties. In this paper, the activity of antiviral agents from medicinal plants which have importance in Ayurveda, are discussed along with their source.

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.

A SYSTEMATIC REVIEW OF EXPERIMENTAL AND CLINICAL STUDIES ON THE PHARMACOLOGY OF GLYCYRRHIZIN AND ITS DERIVATIVES

Glycyrrhizin and its derivatives (glycyrrhizic acid, etc.) are the key components of licorice root extracts (licorice) which can have anti-inflammatory and antiviral effects. A systematic analysis of 3264 publications on the studies of glycyrrhizin and its derivatives made it possible to characterize the range of pharmacological applications of drugs based on glycyrrhizin. The study highlights a number of relevant molecular and cellular mechanisms of action of glycyrrhizin, including regulation of the activity of T-lymphocytes, mast cells, neutrophils, macrophages, biosynthesis and secretion of pro-inflammatory and anti-inflammatory cytokines, lipoxins and prostaglandins. Glycyrrhizin dose-dependently activates receptor LXRa, inhibits the production of pro-inflammatory cytokines IL-6 and IL-8, suppresses the increased expression of HMGB1 receptor and pro-inflammatory cytokines TNF, IL-1ß and IL-6, blocks the NFkB-dependent signaling pathways MAPK and PI3K/Akt, inducible nitric oxide synthase, COX-2. Topical application of glycyrrhizin and its derivatives is promising for the treatment of inflammatory diseases of the mucous membranes and skin, including the diseases of bacterial, fungal and viral origin (allergic contact dermatitis, eczema, keratitis caused by Pseudomonas aeruginosa, papillomavirus, herpes virus (as well as herpes simplex, varicella zoster), SARS-CoV-2, etc. Glycyrrhizin and its derivatives inhibit the formation of biofilms of bacteria characterized by increased resistance to antibiotics and even to antiseptics. Due to the fact that glycyrrhizin induces CD4+ T-cells, it suppresses the production of type 2 cytokines and increases resistance to candidiasis. The study also describes the prospects for the use of glycyrrhizin in the treatment of genital warts. Conclusion: The results of the basic and clinical studies presented in this paper show the prospects for topical application of glycyrrhizin in various fields of medicine, including gynecological practice. © 2022, Bionika Media Ltd.. All rights reserved.