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Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirus

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Abstract

The outbreak of SARS warrants the search for antiviral compounds to treat the disease. At present, no specific treatment has been identified for SARS-associated coronavirus infection. We assessed the antiviral potential of ribavirin, 6-azauridine, pyrazofurin, mycophenolic acid, and glycyrrhizin against two clinical isolates of coronavirus (FFM-1 and FFM-2) from patients with SARS admitted to the clinical centre of Frankfurt University, Germany. Of all the compounds, glycyrrhizin was the most active in inhibiting replication of the SARS-associated virus. Our findings suggest that glycyrrhizin should be assessed for treatment of SARS.

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... It follows from the literature that GL can be active against a wide range of viruses ( Figure 1). GL is used to treat chronic viral hepatitis B and C in China and Japan, its derivatives are used against herpes viruses, alpha, and [4,9]. However, the antiviral activity of GL was demonstrated only in in-P a g e | 303 Prospects for the development of drugs with … vivo experiments on developing chicken embryos and mice, while a detailed analysis of the antiviral action of GL and, most importantly, the main mechanism of the development of the antiviral effect has not been addressed. ...
... However, in vitro studies have not proven the early effect of GL in vivo, i.e. GL does not have direct virucidal activity, but acts indirectly [4,9]. The indirect antiviral effect of GL can be manifested through the cell-virus interaction. ...
... It should be clarified that GL activity is manifested only in the early stages of viral reproduction. When the virus binds to receptors, the virus is captured by cells, or the virus is deproteinized in the cytoplasm [9,10]. Moisy et al. describe another mechanism of the antiviral effect of GL [11]. ...
Article
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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
... The principal phytochemicals extracted from the liquorice roots roots and rhizomes are glycyrrhizin, glycyrrhizic acid or glycyrrhizinic acid. It is also used to treat various diseases like asthma, cough, cold and chronic obstructive pulmonary disease (Cinatl et al., 2003; Hoeyer et al., 2005) [10,16] . ...
... The chief compound glycyrrhizin (a triterpene saponine) was found beneficial against COVID-19 infection by strong affinity to angiotensin converting enzyme 2 which down regulates pro-inflammatory cytokines and also blocks the inhibition of accumulation of intracellular ROS, thrombin, hyperproduction of airways exudates and induces endogenous interferon (Cinatl et al., 2003;Hoeyer et al., 2005;Luo et al., 2020) [10,16,24] . The antiviral capabilities of glycyrrhizin and its active compounds like pyrazofurin, ribavirin, 6-azauridine and mycophenolic acid has been well documented through clinical trials against two corona virus clinical isolates by inhibiting the replication of SARS-CoV-2 virus (Luo et al., 2020) [24] . ...
... The chief compound glycyrrhizin (a triterpene saponine) was found beneficial against COVID-19 infection by strong affinity to angiotensin converting enzyme 2 which down regulates pro-inflammatory cytokines and also blocks the inhibition of accumulation of intracellular ROS, thrombin, hyperproduction of airways exudates and induces endogenous interferon (Cinatl et al., 2003;Hoeyer et al., 2005;Luo et al., 2020) [10,16,24] . The antiviral capabilities of glycyrrhizin and its active compounds like pyrazofurin, ribavirin, 6-azauridine and mycophenolic acid has been well documented through clinical trials against two corona virus clinical isolates by inhibiting the replication of SARS-CoV-2 virus (Luo et al., 2020) [24] . ...
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The coronavirus disease 2019 (COVID-19) caused by the virus Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) has has resulted in massive loss of valuable human lives, extensive destruction of livelihoods and financial crisis of unprecedented levels across the globe and declared a global pandemic in early 2020. The traditional medicine and ayurvedic therapy used in India since ancient times for its multifactorial pharmacological, medicinal, antimicrobial, immunomodulatory and adaptogenic effects, and even during current pandemic as well after recommendation of Ministry of AYUSH (Ayurveda, Yoga and Naturopathy, Unani, Siddha and Homeopathy), Government if India. The commencement of 1206 Ayur Raksha Clinics and associated Task Forces in Indian states during 1 st quarter of 2020 improves the reach and penetration of Ayurvedic preventive, therapeutic and convalescent care strategies for the COVID-19 pandemic. Keeping in view the immunomodulatory, immune system boosting and anti SARS-CoV-2 (anticovid) potential only best eight indigenous flora [Azadirachta indica A.] Amongst several known and recommended medicinal plants were considered in the current manuscript. The ethnomedicinal, pharmacological and clinical significance of these medicinal floras well explored to prove the profound efficacy against SARS-CoV-2 and immunity boosting potential for strengthening of immune system and treatment of COVID-19. Thus, the espousal of the efficient medical flora as profound immunity booster in different formulation like oral pills, powder, decoction or even crude form in daily life is an utmost requirement for the improvement of immune system, treatment, prevention and control of COVID-19 infection.
... It follows from the literature that GL can be active against a wide range of viruses ( Figure 1). GL is used to treat chronic viral hepatitis B and C in China and Japan, its derivatives are used against herpes viruses, alpha, and [4,9]. However, the antiviral activity of GL was demonstrated only in in-P a g e | 303 Prospects for the development of drugs with … vivo experiments on developing chicken embryos and mice, while a detailed analysis of the antiviral action of GL and, most importantly, the main mechanism of the development of the antiviral effect has not been addressed. ...
... However, in vitro studies have not proven the early effect of GL in vivo, i.e. GL does not have direct virucidal activity, but acts indirectly [4,9]. The indirect antiviral effect of GL can be manifested through the cell-virus interaction. ...
... It should be clarified that GL activity is manifested only in the early stages of viral reproduction. When the virus binds to receptors, the virus is captured by cells, or the virus is deproteinized in the cytoplasm [9,10]. Moisy et al. describe another mechanism of the antiviral effect of GL [11]. ...
Article
Full-text available
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 KEYWORDS Coronavirus; licorice root; glycyrrhizic acid; pharmacological effects; nanoparticles
... Licorice is one of those herbs that has been used in traditional Chinese medicine for years (83) Some of the active substances in licorice are glycyrrhizin, liquiritigenin, and glabridin, which exhibit significant antiviral properties (84). The root extract of licorice has been found effective against Influenzae (85), HIV, RSV (86), HBV (83), herpes virus (87), and, most importantly, SARS-CoV-2 (88). ...
... A recent in vitro study found that low zinc levels promote viral growth in SARS-CoV-2 infected cells while, in a complete metal(loid)s investigation, the amount of Zn, Mg, manganese, iron, lead, arsenic, and thallium was lower in severe COVID-19 patients compared to non-COVID-19 patients (174,175). Consequently, control trial and metaanalyzed data revealed that a significant number of COVID-19 patients were Zn deficient (88,175), which was associated with a longer hospital stay and increased mortality, whereas, Zn treatment has been reported to reduce the severity (up to 54%) and duration of various cold symptoms, such as fever, cough, sore throat, muscle pain and nasal congestion (88),which can occur after SARS-CoV-2 infection as well as decreased pneumonia in infants, and decreased mortality (59,123). Although it is unknown whether Zn supplementation can help patients with lower respiratory tract infections, because of its direct antiviral activity, it may alleviate tissue injury caused by mechanical ventilation in COVID-19 patients who are critically ill with low Zn level, and it may be used in conjunction with antiviral drugs to treat COVID-19 infection (169,173). ...
... A recent in vitro study found that low zinc levels promote viral growth in SARS-CoV-2 infected cells while, in a complete metal(loid)s investigation, the amount of Zn, Mg, manganese, iron, lead, arsenic, and thallium was lower in severe COVID-19 patients compared to non-COVID-19 patients (174,175). Consequently, control trial and metaanalyzed data revealed that a significant number of COVID-19 patients were Zn deficient (88,175), which was associated with a longer hospital stay and increased mortality, whereas, Zn treatment has been reported to reduce the severity (up to 54%) and duration of various cold symptoms, such as fever, cough, sore throat, muscle pain and nasal congestion (88),which can occur after SARS-CoV-2 infection as well as decreased pneumonia in infants, and decreased mortality (59,123). Although it is unknown whether Zn supplementation can help patients with lower respiratory tract infections, because of its direct antiviral activity, it may alleviate tissue injury caused by mechanical ventilation in COVID-19 patients who are critically ill with low Zn level, and it may be used in conjunction with antiviral drugs to treat COVID-19 infection (169,173). ...
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SARS-CoV-2, a novel Corona virus strain, was first detected in Wuhan, China, in December 2019. As of December 16, 2021, almost 4,822,472 people had died and over 236,132,082 were infected with this lethal viral infection. It is believed that the human immune system is thought to play a critical role in the initial phase of infection when the viruses invade the host cells. Although some effective vaccines have already been on the market, researchers and many bio-pharmaceuticals are still working hard to develop a fully functional vaccine or more effective therapeutic agent against the COVID-19. Other efforts, in addition to functional vaccines, can help strengthen the immune system to defeat the corona virus infection. Herein, we have reviewed some of those proven measures, following which a more efficient immune system can be better prepared to fight viral infection. Among these, dietary supplements like- fresh vegetables and fruits offer a plentiful of vitamins and antioxidants, enabling to build of a healthy immune system. While the pharmacologically active components of medicinal plants directly aid in fighting against viral infection, supplementary supplements combined with a healthy diet will assist to regulate the immune system and will prevent viral infection. In addition, some personal habits, like- regular physical exercise, intermittent fasting, and adequate sleep, had also been proven to aid the immune system in becoming an efficient one. Maintaining each of these will strengthen the immune system, allowing innate immunity to become a more defensive and active antagonistic mechanism against corona-virus infection. However, because dietary treatments take longer to produce beneficial effects in adaptive maturation, personalized nutrition cannot be expected to have an immediate impact on the global outbreak.
... In addition to, a flavonoid such as quercetin and saponin was isolated from the T. sinensis leaf extract and liquor ice roots, respectively [80,81] showed strong antiviral activity against the SARS coronavirus. These compounds stop the cellular attachment and prevent the entry of virus to the human cell. ...
... Leaf Boiled and drunk [116,117] Allium cepa Bulb Crushed and mixed with honey [118,119] Glycyrrhiza glabra Root Dried roots extracted. The extract is vacuum dried to a dark paste, or maybe dried to a powder [81,120,121] Curcuma longa ...
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COVID-19 is catastrophic widespread in world history. There are many efforts and investments to develop the medicines as far the immune or treat this disease. However, drug and medication are paying to pivot the consideration; it seems from the results of different studies that have been done on plant-originated medicines. These medicines could also be potent candidates for the formulation and development of drugs that inhibit the activity of this virus and control the disease. In this study was discussed the antiviral capability of medicinal isolated natural products and phytochemicals from herbs and plant take part to prohibit the activity of many strains of coronaviruses (CoVs) that cause the diseases in the human. It shows that antiviral plant compounds or molecules is being used for the development of medicines against the CoVs which are responsible for the COVID-19 disease.
... For the study of anti-SARS-CoV-2 drug mechanism, the structure-based screening of chemical or phytochemical databases can provide clues to large numbers of crystal target [136]. A prediction based on molecular simulation showed that the ingredients in Chinese medicine prescriptions such as quercetin [137], andrographolide [138], glycyrrhizic acid [139], baicalin [139,140], patchouli alcohol [141], and luteolin [142] had binding sites against SARS-CoV-2 protein, 3CLpro, ACE2, S protein, Rdrp and PLpro. In addition, their potentially role in the interference of viral life cycles have been previously reported that these components may be able to inhibit virus infection by binding to SARS-CoV-2 protein, inhibiting virus entry into cells, inhibiting the activation of virusinduced cellular pathways, and inhibiting virus replication and proliferation in the body. ...
... For the study of anti-SARS-CoV-2 drug mechanism, the structure-based screening of chemical or phytochemical databases can provide clues to large numbers of crystal target [136]. A prediction based on molecular simulation showed that the ingredients in Chinese medicine prescriptions such as quercetin [137], andrographolide [138], glycyrrhizic acid [139], baicalin [139,140], patchouli alcohol [141], and luteolin [142] had binding sites against SARS-CoV-2 protein, 3CLpro, ACE2, S protein, Rdrp and PLpro. In addition, their potentially role in the interference of viral life cycles have been previously reported that these components may be able to inhibit virus infection by binding to SARS-CoV-2 protein, inhibiting virus entry into cells, inhibiting the activation of virusinduced cellular pathways, and inhibiting virus replication and proliferation in the body. ...
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The pandemic of coronavirus disease 2019 (COVID-19) caused by the SARS-coronavirus 2(SARS-CoV-2) virus has become the greatest global public health crisis in recent years,and the COVID-19 epidemic is still continuing. However, due to the lack of effectivetherapeutic drugs, the treatment of corona viruses is facing huge challenges. In thiscontext, countries with a tradition of using herbal medicine such as China have beenwidely using herbal medicine for prevention and nonspecific treatment of corona virusesand achieved good responses. In this review, we will introduce the application of herbalmedicine in the treatment of corona virus patients in China and other countries, andreview the progress of related molecular mechanisms and antiviral activity ingredients ofherbal medicine, in order to provide a reference for herbal medicine in the treatment ofcorona viruses. We found that herbal medicines are used in the prevention and fightagainst COVID-19 in countries on all continents. In China, herbal medicine has beenreported to relieve some of the clinical symptoms of mild patients and shorten the length of hospital stay. However, as most herbal medicines for the clinical treatment of COVID-19still lack rigorous clinical trials, the clinical and economic value of herbal medicines in theprevention and treatment of COVID-19 has not been fully evaluated. Future work basedon large-scale randomized, double-blind clinical trials to evaluate herbal medicines andtheir active ingredients in the treatment of new COVID-19 will be very meaningful.
... GL can inhibit the adsorption and penetration of viruses in the early stages of the replication cycle, as well as inhibit the replication of clinically isolated coronaviruses (FFM-1 and FFM-2). The underlying mechanism may involve regulating and inducing the expression of nitrous oxide synthase and production of nitrous oxide in macrophages [127]. Such findings indicate that adding GL after virus adsorption is more effective than adding GL during adsorption. ...
... Notably, the solubility and bioavailability of some TCM components, such as polysaccharides, resveratrol, quercetin, baicalin, curcumin, emodin, and tanshinone IIA are limited, which leads to poor blood absorption following oral administration. Such compounds may exert their therapeutic effects through interaction with intestinal microbes [127]. ESP-B4 is a homogeneous polysaccharide isolated from E. sinica, with a uronic acid content of 77.5% and relative molecular weight of 23 kD. ...
... Nacetylmuramoyl is a glycyrrhizin analog that has shown the potential for in vitro immune stimulation (Dissanayake et al., 2020). In a study, Cinatl et al. (2003) compared the antiviral efficacy of 6-azouridine, glycyrrhizic acid, mycophenolic acid, pyrazofurin, and ribavirin, on SARS-COV. The experimental results showed that glycyrrhizic acid has a better antiviral activity as compared to the other four drugs in viral adsorption and penetration (Cinatl et al., 2003). ...
... In a study, Cinatl et al. (2003) compared the antiviral efficacy of 6-azouridine, glycyrrhizic acid, mycophenolic acid, pyrazofurin, and ribavirin, on SARS-COV. The experimental results showed that glycyrrhizic acid has a better antiviral activity as compared to the other four drugs in viral adsorption and penetration (Cinatl et al., 2003). It was found that glycyrrhizin possesses the ability to stimulate endogenous defense mechanisms (Arora et al., 2011). ...
Article
Ethnopharmacological relevance The coronavirus disease (COVID-19) has relentlessly spread all over the world even after the advent of vaccines. It demands management, treatment, and prevention as well with utmost safety and effectiveness. It is well researched that herbal medicines or natural products have shown promising outcomes to strengthen immunity with antiviral potential against SARS-COV-2. Aim of the review: Our objective is to provide a comprehensive insight into the preventive and therapeutic effects of herbal medicines and products (Ayurvedic) for pre-and post-COVID manifestations. Material and method The database used in the text is collected and compiled from Scopus, PubMed, Nature, Elsevier, Web of Science, bioRxiv, medRxiv, American Chemical Society, and clinicaltrials.gov up to January 2022. Articles from non-academic sources such as websites and news were also retrieved. Exploration of the studies was executed to recognize supplementary publications of research studies and systematic reviews. The keywords, such as “SARS-COV-2, coronavirus, COVID-19, herbal drugs, immunity, herbal immunomodulators, infection, herbal antiviral drugs, and WHO recommendation” were thoroughly searched. Chemical structures were drawn using the software Chemdraw Professional 15.0.0.160 (PerkinElmer Informatics, Inc.). Result A plethora of literature supports that the use of herbal regimens not only strengthen immunity but can also treat SARS-COV-2 infection with minimal side effects. This review summarizes the mechanistic insights into herbal therapy engaging interferons and antibodies to boost the response against SARS-COV-2 infection, several clinical trials, and in silico studies (computational approaches) on selected natural products including, Ashwagandha, Guduchi, Yashtimadhu, Tulsi, etc. as preventive and therapeutic measures against COVID. We have also emphasized the exploitation of herbal medicine-based pharmaceutical products along with perspectives for unseen upcoming alike diseases. Conclusion According to the current state of art and cutting-edge research on herbal medicines have showed a significant promise as modern COVID tools. Since vaccination cannot be purported as a long-term cure for viral infections, herbal/natural medicines can only be considered a viable alternative to current remedies, as conceived from our collected data to unroot recurring viral infections.
... It has been suggested an effective inhibitor which is used against the numerous pathogenic flaviviruses. But the mechanism of action of Glycyrrhizin is not clear [42]. similarly, baicalin (flavonoid compound) antiviral activity has been observed against SARS coronavirus obtained from an herb Scutellaria baicalensis Georgi in China and Hong Kong [19]. ...
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The COVID-19 has shown to be responsible for respiratory illness outbreak within Hubei province of Wuhan in China that began in December, 2019. The virus has spread to about 192 countries. This review analyzed a number of research articles published till December, 2021 in order to understand the causes, diagnosis, control and prevention of such virus. Studies until now have revealed that its origination has a link to a sea- food market within Wuhan, but no precise association of animals has confirmed. The symptoms comprise fatigue, dry cough, fever, pneumonia, headache, dyspnea and diarrhea. Preventive measures like avoidance of public contact, contact tracing, hand hygiene practices, masks, quarantines and case detection are suggested for lowering the transmission. Up to now, several precise anti-viral treatment and effective vaccines are available for the control of COVID-19. Therefore, affected individuals mainly depends on supportive care, symptomatic treatment, antiviral therapy and available vaccines.
... Kaempferol derivatives including Juglanin, tiliroside & afzelin acts as inhibitors of 3a ion channel protein and hinders viral shedding [41]. Glycyrrhizin and luteolin, a saponin and a flavonoid respectively, has been reported to be effective against SARS-CoV by inhibiting adsorption and penetration of the virus in the early phase of the replication cycle by interfering with 3CL pro and spike protein of the SARS CoV [42,43]. CoV main protease plays a crucial role in processing viral polyproteins and regulatng replication. ...
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The COVID-19 crisis has alerted the research community to re-purpose scientific tools that can effectively manage emergency pandemic situations. Researchers were never so desperate to discover a ‘magic bullet’ that has significant clinical benefits with minimal or no side effects. At the beginning of the pandemic, due to restricted access to traditional laboratory techniques, many research groups delved into computational screening of thousands of lead molecules that could inhibit SARS-CoV-2 at one or more stages of its infectious cycle. Several in silico studies on natural derivatives point out their potency against SARS-CoV-2 proteins. However, theoretical predictions and existing knowledge on related molecules reflect their poor oral bioavailability due to biotransformation in the gut and liver. Nanotechnology has evolved into a key field for precise and controlled delivery of various drugs that lack aqueous solubility, have low oral bioavailability and possess pronounced toxicity in their native form. In this review, we discuss various nanoformulations of natural products with favorable ADME properties, and also briefly explore nano-drug delivery to lungs, the primary site of SARS-CoV-2 infection. Natural products are also envisioned to augment nanotechnology-based 1) personnel protective equipment for ex vivo viral inactivation and 2) wearable sensors that perform rapid and non-invasive analysis of volatile organic compounds in exhaled breath of the infected person after therapeutic food consumption.
... The glycyrrhizin are most active in inhibiting the replication of the SARS-associated virus. [31] Glycyrrhizin has a low selectivity index, but was a significantly potent inhibitor of replication of all the viruses tested. The mechanism of glycyrrhizin's activity against SARS-CV is unclear, But Glycyrrhizin are affects cellular signalling pathways such as protein kinase C; casein kinase II and transcription factors such as activator protein. ...
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More than 1,100 people have died after an outbreak of coronovirus in the central Chinese city of Wuhan, after that World Health Organisation has declared a global health emergency in World. The Corona Virus is an enveloped single-stranded RNA virus belonging to the family Coronaviridae. It causes a variety of diseases in mammals and birds but, in the last few decades, has shown to be capable of infecting humans as well. The outbreak of severe acute respiratory syndrome (SARS) in 2003 and, more recently, Middle-East respiratory syndrome (MERS) has demonstrated the lethality of CoVs when they cross the species barrier and infect humans. News reports of patients with an unknown pneumonia were first identified on 31 st December with the Wuhan Municipal Health Commission. On 1st January 2020, the seafood market was closed and decontaminated while countries with travel links to Wuhan went on high alert for potential travelers with unexplained respiratory disease.
... Not only did GLR decrease viral multiplication, it also prevented viruses from adhering to and entering cell membranes. A drug-induced increase in nitrous oxide synthase was noted at the time, suggesting nitrous oxide might be responsible for the suppression of viral multiplication at that time [68,69]. ...
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Optimized therapeutic bio-compounds supported by bio-acceptable nanosystems (i.e., precise nanomedicine) have ability to promote health via maintaining body structure, organ function, and controlling chronic and acute effects. Therefore, nano-nutraceuticals (designed to neutralize virus, inhibit virus bindings with receptors, and support immunity) utilization can manage COVID-19 pre/post-infection effects. To explore these approaches well, our mini-review explores optimized bio-active compounds, their ability to influence SARS-CoV-2 infection, improvement in performance supported by precise nanomedicine approach, and challenges along with prospects. Such optimized pharmacologically relevant therapeutic cargo not only affect SARS-CoV-2 but will support other organs which show functional alternation due to SARS-CoV-2 for example, neurological functions. Hence, coupling the nutraceuticals with the nano-pharmacology perspective of higher efficacy via targeted delivery action can pave a novel way for health experts to plan future research needed to manage post COVID-19 infection effect where a longer efficacy with no side-effects is a key requirement.
... The buffer was freshened after every interval. The samples were weighted after 1, 2,5,8,12,18,24,48, and 72 h. The ratio of swelling at time t was calculated using the following equation ECW was also calculated for each sample: we consider the that swelling ratio is equal to ECW, if the weight of the swollen hydrogel did not change in time significantly. ...
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The COVID-19 virus is spread by pulmonary droplets. Its high infectivity is caused by the high-affinity binding of the viral spike protein to the ACE2 receptors on the surface of respiratory epithelial cell membranes. The proper hydration of nasal mucosa plays an essential role in defense of bacterial and viral infections. Therefore, a nasal formulation, which can moisture the nasal mucosa and contains the ACE2 receptor inhibitor, can reduce the risk of COVID-19 infection. This article presents a systematic study of the preparation of chitosan hydrogels with dicarboxylic acids (malic and glutaric acid) and their detailed characterization (Fourier transform infrared spectroscopy, determination of cross-linking efficiency, rheological studies, thermal analysis, and swelling kinetics). The results confirm that chemically cross-linked chitosan hydrogels can be synthesized using malic or glutaric acid without additives or catalysts. The adsorption capacity of hydrogels for three different ACE2 inhibitors, as APIs, has also been investigated. The API content of hydrogels and their mucoadhesive property can provide an excellent basis to use the hydrogels for the development of a nasal formulation in order to reduce the risk of SARS-CoV 2 infection.
... Furthermore, GL was found to inhibit the replication, adsorption, and penetration of SARS-associated coronavirus (SARS-CoV), without inducing cytotoxic effect to the host cells (Cinatl et al., 2003). The action mechanism of GL is still not completely understood, however, the effect of GL could be linked to its ability to produce nitrous oxide synthase, which could inhibit viral replication (Bailly and Vergoten, 2020). ...
Article
Background Glycyrrhizin (GL) is a major active constituent of licorice root (Glycyrrhiza glabra) that is considered one of the oldest and most frequently employed botanicals in Chinese medicine and worldwide, with most effects attributed to its rich GL content. Structurally, GL a triterpene saponin that is widely used as a flavoring agent in foodstuffs and cosmetics, and also proposed for various clinical applications with a myriad of health benefits. Pharmacological and biological activities of GL include antiviral, anti-inflammatory, antioxidant, and anticancer activities (in vitro and in vivo). Currently, there is no comprehensive review on GL biological effects and its action mechanisms. Purpose This review summarizes GL pharmacological actions from a molecular biology perception, presented on its metabolism and side effects based on in vitro, in vitro and clinical studies. Moreover, the potential of GL as a nanomedicine delivery system is also summarized. The progress in drug delivery research using GL presented herein is expected to provide a theoretical basis for developing other novel drugs formulations. Methods A systematic review was carried out in several electronic databases (Science Direct, SpringerLink, CNKI, PubMed, Web of Science, Elsevier, and Scopus), using the following key words: glycyrrhizin “AND” bioactivity “OR” clinic “OR” therapeutic “OR” drug delivery. This search included manuscripts published between 1989 and 2021. Results 126 researches were selected and summarized in this review. The analysis of these studies indicated that GL has antiviral activity against different viruses. Further, GL efficiently suppressed the respiratory manifestations associated with COVID-19 by reducing the expression of angiotensin converting enzyme 2 (ACE2) that employed by the virus as an entry point. Otherwise, GL was found to induce antioxidant, anti-inflammatory, immune-modulatory, and anticancer activity. Besides, diminution the particle size of GL to nanometer size significantly augments their action and biodistribution. Conclusion This article summarizes the pharmacological actions of GL. The potential of GL as a nanomedicine delivery system is also presented. Nevertheless, most studies reported provide no deep insight of GL health effects warranting for more future studies to elucidate its action mechanism and potential therapeutic benefits through preclinical and clinical trials.
... Radix glycyrrhizae (Gancao), its active ingredient glycyrrhizin could potently inhibit replication of clinical isolates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). (20) Moreover, Semen armeniacae amarum (Xingren), with property of relieving cough and asthma, and its active ingredient, amygdalin, can inhibit pulmonary fibrosis. (21) Herba agastachis (Huoxiang) could remove cold and dampness and dry up Spleen. ...
Article
Objectives To summarize the measures and rules of Chinese medicine (CM) and provide reference for clinical application in the prevention and treatment of coronavirus disease (COVID-19).Methods The data source was from CM COVID-19 prevention and treatment programs on government websites and official media websites of the different provinces and cities. The search lasted from December 8, 2019 to March 10, 2020. Main variables were medication frequency and combinations of medicines. Cluster analysis and complex network analysis were used by prevention and treatment stage and by area.ResultsAmong 27 CM diagnosis and treatment plans, 203 therapeutic prescriptions were enrolled, of which the top 4 herbs were: Radix glycyrrhizae, Semen armeniacae amarum, Herba ephedrae, and Herba agastachis, respectively. The core combinations were Herba ephedrae and Semen armeniacae amarum. Forty-eight preventive formulae were identified. Ten herbs, including Radix Astragali seu hedysari, Radix glycyrrhizae, Radix saposhnikoviae, Flos lonicerae, etc. were most frequently used. The core prescription of CM compatibility was Radix astragali seu hedysari, Radix glycyrrhizae, and Radix saposhnikoviae, which is the main component of Yu Ping Feng San. There were 45 prevention and treatment prescriptions in East China; the most used CM was Radix glycyrrhizae, Herba agastachis, Pericarpium citri reticulatae, and Gypsum fibrosum. Fifty prescriptions were identified in North China. According to CM analyses, Herba agastachis, Semen armeniacae amarum, Herba ephedrae, and Poria were most frequently used.ConclusionsCM for COVID-19 prevention mainly focuses on improving human immunity; for treatment, prescription focuses on clearing the lungs and removing dampness. Prescriptions vary with regions, perhaps due to climatic and environmental differences, which help clinicians to quickly make CM plans and treat patients according to clinical status, further minimizing resource wastage.
... Science has long been suggesting the antiviral effects of plants, which were evaluated for exhibiting activity against Severe Acute Respiratory Syndrome (SARS) and SARScorona virus (SARS-CoV) [27,18]. However, there are few tools to test the ability of these viruses to infect humans, which makes it difficult to approach possible solutions in a subsequent zoonotic outbreak. ...
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Introduction: It is important to find tools to help patients and prevent viral diffusion of pneumonia caused by the 2019 novel coronavirus (2019-nCoV or SARS-CoV-2). Recent articles have reported site-specific SARS-CoV-2 infection on a patient's body, specifically a very active replication in the throat and upper respiratory tract, even at the mild stage of the disease, which shows its efficient viral transmission in sputum. Materials and Methods: An alternative that may be feasible is to resort to scientific studies that demonstrate the antiviral potential of medicinal plants species through in-vitro and in-vivo experiments to alleviate symptoms and prevent the spread of contagion. A literature search on Scopus and PubMed on herbs and foods with antiviral properties was performed. Results: This resulted in hundreds of publications showing a diversity of plants with antiviral effects against different virus infections. This article focuses on plants that are of common use, which could act against COVID-19. Conclusion: Herbs and foods with demonstrated antiviral potential have been identified, limiting SARS-CoV-2 spread by interfering with ACE2 protein on infection sites. The analysis of transdisciplinary knowledge allows us to connect previous research on the action of common plants and foods on viruses to limit the replication of SARS-CoV-2 in the throat and upper respiratory tract.
... Ribavirin was initially used, but it turned out to be an almost ineffective drug and shows serious side effects (16,17). Interferon was initially reported to exhibit an anti-COVID-19 effect (18), and glycyrrhizin was also found to be effective (19), but then the hope for them lost rapidly. Although some antimalarial drugs such as hydroxychloroquine or some antiviral drugs like favipiravir or remdesivir are recommended, the exact effect has not been revealed. ...
Article
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Severe acute respiratory syndrome (SARS) is an infectious and highly transmissible disease that is affected by SARS coronavirus (SARS-CoV) and for which there are presently no approved treatments. COVID-19 is a new strain of coronavirus that has not been previously identified in humans. It is also a member of the coronaviruse family and known to cause similar illnesses in humans. The last outbreak has been identified as a Pandemic because of COVID-19 infections in humans. This review has been prepared to give some information to readers or scientists about some new generation of boron-doped or boron attached composite quantum dots during the design phase of the drug or drug delivery systems to be developed to combat COVID-19 and to help in the design of new drugs and systems by opening some new horizons. All scientists and researchers must quickly share their ideas and experiences in the fight against COVID-19 to find a better therapy or strategy for humans, and thus we can be successful. In this sense, this review offers readers some new ideas and rational perspectives. In conclusion, boron-containing composite carbon quantum dots appear to be the most suitable delivery system for treating COVID-19 infections especially when they are delivered through the lung.
... The latest studies and reviews focus the attention on S-containing polysaccharides (Chitosan [146] and semisynthetic derivatives [147], kappa-, iota-, lambda-Carrageenan [148][149][150], Fucoidan [150][151][152]), Lactoferrin [153,154], Aloe vera polysaccharides [155], the flavonoids Hesperidin [14,156,157], Hispidulin [158], Quercetin [153], Rutin [159], Resveratrol [160], the saponin Glycyrrhizin [161], and the diterpenoid Andrographolide [162,163]. Many of them possess not only the ability to block the adhesin-receptor connection and following viral entry, but are also proven to exhibit antiviral activity due to inhibition of viral replication (Chitosan and other sulfated polysaccharides [145,164,165], Resveratrol [166,167], Aloe vera polysaccharides [155], Glycyrrhizin [168], Andrographolide [169]), inhibition of protein synthesis (Aloe vera polysaccharides [155] and Andrographolide [169]), blocking the viral release and spread (Andrographolide [169]), and/or immunomodulatory properties (Chitosan [170]). The antiviral potency of other biomolecules is primarily due to interference in one or multiple steps of the infectious cycle of pathogens (i.e., after adhesion) and by activating the host immunomodulatory system. ...
Article
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In this time of COVID-19 pandemic, the strategies for prevention of the infection are a primary concern. Looking more globally on the subject and acknowledging the high degree of misuse of protective face masks from the population, we focused this review on alternative pharmaceutical developments eligible for self-defense against respiratory infections. In particular, the attention herein is directed to the nasal and oromucosal formulations intended to boost the local immunity, neutralize or mechanically “trap” the pathogens at the site of entry (nose or mouth). The current work presents a critical review of the contemporary methods of immune- and chemoprophylaxis and their suitability and applicability in topical mucosal dosage forms for SARS-CoV-2 prophylaxis.
... The antiviral properties of functional foods have also been documented to be effective against different viruses. Glycyrrhizin is effective against Japanese encephalitis virus, Human immunodeficiency virus type 1 (HIV-1), and chronic hepatitis C virus (HCV) [62]. Glycyrrhizin in licorice roots has been shown to inhibit SARS-CoV replication as it affects cellular signaling pathways and induces nitrous oxide synthesis in macrophages, preventing the virus from replicating [12]. ...
Article
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Background The novel coronavirus has embarked on a global pandemic and severe mortality with limited access for its treatments and medications. For the lack of time, research, and enough efficacy, most vaccines are underdeveloped or unreachable to society. However, many recent studies suggest various alternative, complementary remedies for COVID-19, which are functional foods. This review provides an overview of how functional foods can play a great role through modulating the host immune system, generating antiviral activities, and synthesizing biologically active agents effective against the coronavirus. Main body This review article summarizes the natural defense mechanisms in tackling SARS-CoV-2 alongside conventional therapeutic options and their corresponding harmful side effects. By analyzing bioactive components of functional foods, we have outlined its different contributions to human health and its potential immunomodulatory and antiviral properties that can enhance resistivity to viral infection. Moreover, we have provided a myriad of accessible and cost-effective functional foods that could be further investigated to target specific key symptoms of COVID-19 infections. Finally, we have found various functional foods with potent bioactive compounds that can inhibit or prevent COVID-19 infections and disease progression. Short conclusion Numerous functional foods can help the body fight COVID-19 through several mechanisms such as the reduced release of pro-inflammatory cytokines, reduced expression of ACE2 receptors in cells, and inhibiting essential enzymes in SARS-CoV-2.
... [2] A trial analysis of a coronavirus extracted from SARS clinical patients published in The Lancet in 2003 showed that glycyrrhizin extracted from licorice root produces NO release effect, thereby inhibiting the replication of SARS virus. [39] In a small clinical study in Beijing during the SARS prevention and treatment period in 2004, inhaling NO gas in 6 patients reduced airway resistance, increased arterial oxygen partial pressure and oxygen saturation. [40] Interestedly, after stopping NO gas inhalation, chest radiograph displayed improvement in the density and area of lung infiltration, and physiological functions continued to be improved. ...
Article
The ongoing outbreak of COVID-19 has quickly become a daunting challenge to global health. In the absence of satisfied therapy, effective treatment interventions are urgently needed. Previous studies have demonstrated that acupuncture is effective at relieving common symptoms of COVID-19 including breathlessness, nausea, insomnia, leukopenia, fatigue, vomiting, and abdominal pain. Experiments have shown that nitric oxide (NO) inhibits the replication cycle of severe acute respiratory syndrome (SARS) coronavirus with similar structures of COVID-19. Increase in level of NO by using NO gas inhalation has been shown to restore lung function by reducing airway resistance and improving virus-induced lung infections in SARS patients. Recent case report showed that a medical acupuncturist with symptoms consistent with severe COVID pneumonia achieved full recovery by self-administered medical acupuncture and cupping therapy at home. Clinical features and pathophysiology demonstrated that NO deficiency and endothelial dysfunction contribute to the development of COVID-19. Several studies from different groups consistently demonstrated that acupuncture increases NO synthase expression and induces an elevation of NO production and release in plasma and the local skin regions in both animals and humans. It is suggested that exogenous NO supplies or interventions that induce increasing levels of NO can play an important role in protective effects against inflammation and acute lung injury. This article reviews the rationale for mechanisms of NO induction induced by acupuncture in the possible treatment of COVID-19 and highlights its potential for contributing to better clinical outcomes and improving future clinical studies of acupuncture on treatment of COVID-19.
... G. glabra possesses antibacterial, antioxidant, antimalarial, antispasmodic, anti-inflammatory, anti-hyperglycemic properties, antiulcer, antiviral, antihepatotoxic, antifungal, and herpes simplex inhibitory activities 25 . In an earlier study, glycyrrhizin was found to be most active in inhibiting replication of the SARS-associated virus 29 . Prepared derivatives of glycyrrhizin have shown 10-fold increased anti-SARS-CoV activity compared to glycyrrhizin. ...
Article
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The recent threat which has received worldwide attention is COVID-19, a rapidly spreading new strain of Coronavirus. It has affected more than 176 countries and due to the lack of efficacious drugs or vaccines against SARS-CoV-2, it has further worsened the situation everywhere. After infecting the host, the ssRNA genome of SARS-CoV-2 is translated into a large polyprotein which will be further processed into different nonstructural proteins to form a viral replication complex by the virtue of virus-specific proteases namely main protease (3-CL protease) and papain protease. The crystallized form of SARS-CoV-2 main protease (Mpro) is demonstrated to be a novel therapeutic drug target according to current research. The present study was conducted to evaluate the efficacy of few plant-based bioactive compounds against COVID-19 Mpro (PDB ID: 6LU7: Resolution 2.16 Å) by molecular docking study. Molecular docking investigations were performed by using Auto DockVina to analyze the inhibition capacity of these compounds against COVID-19 as a whole complex and also in the absence of Chain C which is present with protein as a peptide. According to the obtained results, Ritonavir and Curcuminwere found to be more effective on COVID-19 than nelfinavir which is an anti-HIV drug. This is followed by Glycyrrhizin and Piperine, which correlates with COVID-19 as a whole complex and also in the absence of Chain C. So, this study will pave a way for performing more advanced experimental research and to evaluate the natural compounds to cure COVID-19.
... These compounds also inhibited the expression of inflammatory cytokines induced by the virus and regulated the activity of NF-κB/MAPK and RIG-1/STAT-1/2 signalling pathways in vitro. 41 Glycyrrhizin (GR) from G. glabra has been reported to act against the influenza virus by inhibiting viral adsorption onto the host cell (ie, virus uptake) with reduced endocytotic activity, which augments viral replication inhibition. 42 It has also been found effective against SARS-CoV. ...
Article
The COVID-19 pandemic has posed a significant threat to human health due to the lack of drugs that can potentially act against SARS-CoV-2. Also, even after the emergency approval of WHO, the vaccines’ efficacy is still a question, and people are getting reinfections. Previous studies have demonstrated the efficacy of traditional medicinal plants against influenza and SARS coronavirus. The present article aims to review potential phytochemicals from Indian medicinal plants that may be used against SARS-CoV-2. Articles published in the English language between 1992 and 2021 were retrieved from Embase, PubMed, and Google scholar using relevant keywords, and the scientific literature on efficacies of Indian medicinal plants against SARS-CoV and influenza virus were analyzed. The initial search revealed 1304 studies, but, on subsequent screening, 115 eligible studies were reported. Twenty research articles investigating traditional medicinal plant extracts and metabolites against SARS-CoV and influenza A virus in in vitro and in vivo systems satisfied the search criteria. The studies reported that plant extracts and active compounds such as glycyrrhizin, 14-α-lipoyl andrographolide, and curcumin from medicinal plants such as Yashtimadhu (Glycyrrhiza glabra), Bhunimba (Andrographis paniculata), and Haridra (Curcuma longa) are effective against the various phases of the virus life cycle, viz., virus-host cell attachment, viral replication, 3CL protease activity, neuraminidase activity, adsorption and penetration of the virus. As per ancient Indian literature, plants in Ayurveda possess Rasayana (revitalizing) and Jwara hara (antipyretic, anti-inflammatory) properties. This evidence may be used to conduct experimental and clinical trials to study the underlying mechanisms and efficacy of antiviral properties of Indian medicinal plants against SARS-CoV-2.
... Bioactive components of Yastimadhu (Glycyrrhiza glabra; licorice) root were found to inhibit adsorption, penetration, and replication of SARS-CoV-2 in vitro (Cinatl et al., 2003;Pompei et al., 1979). Molecular docking experiments revealed that licorice's active constituents demonstrated a strong binding affinity with various viral proteins such as S protein, Main Protease (Mpro), and RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2, as well as human furin protease and the ACE2 receptor (Maurya, 2020) (Table 1). ...
Article
Introduction The need for specific therapeutics against infectious diseases is made very important at this moment by the COVID-19 pandemic caused by SARS-COV-2. Vaccines containing live attenuated or heat-inactivated pathogens elicit robust immune responses, but their safety is sometimes not assured. Subunit vaccines consisting of the most potent antigenic protein or carbohydrates of the pathogen are safer but often induce a weak immune response. Traditional Ayurveda medicines have a long history of safety and may act as immuno-modulators or vaccine adjuvants. They can reduce the amount of vaccine booster doses required to elicit an immune response against any pathogen. The main objective of this review is a mechanistic evaluation of the antiviral potential of Ayurveda herbal compositions for their ability to increase cytokine expression and enhance NK cell activity, activate CD4/ CD8+ T cells, and increase the formation of IL-2 and IFNγ against SARS-CoV-2 infection. Methods Various peer-reviewed publications, books, monographs, and reputed search engines were reviewed in depth. Information available from the Ayurvedic Pharmacopoeia and in recent in silico analyses were compared in order to understand the mechanism of action of herbal components against SARS-CoV-2. Results It was found in various molecular docking and molecular dynamics studies that many bioactive natural components of Ayurvedic medicines could prevent viral entry or multiplication within a human host. Conclusion Ayurvedic herbal medicines can be used either independently as therapeutics or as a complement to the modern-day recombinant vaccines with immediate effect. Ayurveda-based adjuvant therapy can also efficiently manage the secondary symptoms of COVID 19 patients.
... Hundreds of herbal products were screened for their possible effects against coronaviruses. After the first outbreak of SARS-CoV, glycyrrhizin (a saponin from Liquorice roots) demonstrated its ability to inhibit the replication of SARS-associated coronavirus (EC 50 300-600 mg/L) providing a substitute to Ribavirin causing hemolysis and a significant drop in haemoglobin levels in SARS patients (Cinatl et al., 2003), while the inclusion of 2-acetamido-β-D-glucopyranosylamine into the glycoside chain of glycyrrhizin leads to a 10-fold increase in its activity (Hoever et al., 2005). Studies showed that pharmacological candidates either inhibit viral entry and replication or elicit an immune reaction to yield type I IFN against SARS-CoV (Báez-Santos et al., 2015;Kim et al., 2011). ...
Article
The challenge continues globally triggered by the absence of an approved antiviral drug against COVID-19 virus infection necessitating global concerted efforts of scientists. Nature still provides a renewable source for drugs used to solve many health problems. The aim of this work is to provide new candidates from natural origin to overcome COVID-19 pandemic. A virtual screening of the natural compounds database (47,645 compounds) using structure-based pharmacophore model and molecular docking simulations reported eight hits from natural origin against SARS-CoV-2 main proteinase (Mpro) enzyme. The successful candidates were of terpenoidal nature including taxusabietane, Isoadenolin A & C, Xerophilusin B, Excisanin H, Macrocalin B and ponicidin, phytoconstituents isolated from family Lamiaceae and sharing a common ent-kaurane nucleus, were found to be the most successful candidates. This study suggested that the diterpene nucleus has a clear positive contribution which can represent a new opportunity in the development of SARS-CoV-2 main protease inhibitors.
... 20 Moreover, anti-inflammatory effects of glycyrrhizin have been documented and are exerted through the Toll-like receptor 4. 20 In 2003, at the time of severe acute respiratory syndrome outbreak, a study from Germany reported that glycyrrhizin was quite potent at inhibiting the replication of severe acute respiratory syndrome coronavirus in vitro, and concluded that glycyrrhizin should be investigated as a potential treatment. 22 Pharmacologic pathways that have been proposed for the potential of glycyrrhizin in the treatment of COVID-19 ...
Article
Coronavirus disease 2019 (COVID-19) pandemic has caused an urgent need for investigating potential treatments. Traditional medicine offers many potential remedies that have been historically used and have the advantage of bypassing the cultural obstacles in the practice of medicine. We aimed to investigate the efficacy of Zufa syrup in the treatment of suspected patients with mild to moderate symptoms of COVID-19. This triple-blind randomized controlled trial recruited patients with evidence of COVID-19 on chest computed tomography without an indication of hospital admission from March 2020 until April 2020. Participants were assessed by a physician and completed a pre-specified form to assess the duration and severity of symptoms. Patients were randomized to receive Zufa syrup (a combination of herbal medicines: Nepetabracteata, Ziziphus jujube, Glycyrrhizaglabra, Ficuscarica, Cordia myxa, Papaver somniferum, Fennel, Adiantumcapillus-veneris, Viola, Viper's-buglosses, Lavender, Iris, and sugar) or identical-looking placebo syrup at a dose of 7.5 mL (one tablespoon) every 4 hours for 10 days. After applying the eligibility criteria, 116 patients (49.1% male) were randomized to trial arms with a mean age of 44.3. During the follow-up, Cough, dyspnea, headache, myalgia, anorexia, anxiety, and insomnia improved gradually in both groups, and showed no difference between Zufa syrup and placebo. Oxygen saturation and pulse rate had stable trends throughout the follow-up and were similar between study arms. No patient required hospital admission or supplemental oxygen therapy during the study period. To conclude, in patients with mild to moderate symptoms of COVID-19, Zufa syrup did not show any difference in symptomatology over a 10 days' period when compared with placebo. Due to potential effects of medicinal plants in the treatment of respiratory infections, further studies are warranted to clarify their role in COVID-19. The study was approved by the Ethics Committee of the Qom University of Medical Science (Ethics committee reference number IR.MUQ.REC.1398.165) on March 10, 2020 and was registered in Iranian Clinical Trial Center (approval ID: IRCT20200404046934N1) on April 13, 2020.
... In literature, it has been reported that phytochemicals of Glycyrrhiza glabra are potent against SARS-CoV. The two major phytochemicals namely, glycyrrhizin (46) and glycyrrhizic acid (47) exhibit more potent antiviral activity against SARS-CoV (Cinatl et al., 2003;Hoever et al., 2005). Further studies have revealed that the addition of 2-acetamido-b-D-glucopyranosylamine into the glycoside chain of glycyrrhizin (46) produced a ten-fold potency against SARS-CoV (Hoever et al., 2005). ...
Article
The widespread COVID-19 pandemic, caused by novel coronavirus SARS-CoV-2, has emanated as one of the most life-threatening transmissible diseases. Currently, the repurposed drugs such as remdesivir, azithromycine, chloroquine, and hydroxychloroquine are being employed in the management of COVID-19 but their adverse effects are a matter of concern. In this regard, alternative treatment options i.e., traditional medicine, medicinal plants, and their phytochemicals, which exhibit significant therapeutic efficacy and show a low toxicity profile, are being explored. The current review aims at unraveling the promising medicinal plants, phytochemicals, and traditional medicines against SARS-CoV-2 to discover phytomedicines for the management of COVID-19 on the basis of their potent antiviral activities against coronaviruses, as demonstrated in various biochemical and computational chemical biology studies. The review consists of integrative and updated information on the potential traditional medicines against COVID-19 and will facilitate researchers to develop traditional medicines for the management of COVID-19.
... In in silico work, it has been shown that terpene Ginkgolide A can strongly inhibit the SARS CoV-2 protease enzyme [12]. In addition, Glycyrrhizin, a triterpene found in licorice roots, could inhibit SARS-CoV replication in vitro [77] and its efficacy was also obtained in patients [78]. Squalene, a natural triterpene which is a precursor of sterols and other bioactive terpenoids, was extracted from pumpkin seed oil. ...
Article
Full-text available
Coronavirus illness (COVID-19) is an infectious pathology generated by intense severe respiratory syndrome coronavirus 2 (SARS-CoV-2). This infectious disease has emerged in 2019. The COVID-19-associated pandemic has considerably affected the way of life and the economy in the world. It is consequently crucial to find solutions allowing remedying or alleviating the effects of this infectious disease. Natural products have been in perpetual application from immemorial time given that they are attested to be efficient towards several illnesses without major side effects. Various studies have shown that plant extracts or purified molecules have a promising inhibiting impact towards coronavirus. In addition, it is substantial to understand the characteristics, susceptibility and impact of diet on patients infected with COVID-19. In this review, we recapitulate the influence of extracts or pure molecules from medicinal plants on COVID-19. We approach the possibilities of plant treatment/co-treatment and feeding applied to COVID-19. We also show coronavirus susceptibility and complications associated with nutrient deficiencies and then discuss the major food groups efficient on COVID-19 pathogenesis. Then, we covered emerging technologies using plant-based SARS-CoV-2 vaccine. We conclude by giving nutrient and plants curative therapy recommendations which are of potential interest in the COVID-19 infection and could pave the way for pharmacological treatments or co-treatments of COVID-19.
... Thus, the repurposing of natural products could be an efficient strategy against SARS-CoV-2 infection [3]. Some natural compounds have been shown to possess antiviral activities against various viruses (influenza virus, human immunodeficiency virus (HIV), hepatitis C and B viruses, measles-virus, herpes simplex virus, poliovirus and human coronaviruses SARS and MERS) [4][5][6][7][8][9][10][11]. The potential treatments for viral diseases using natural plant compounds are actively studied worldwide, especially against viruses from the coronavirus group were intensified last year. ...
Article
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Background: A novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become the leading threat to global health. An effective antiviral could not only help those still vulnerable to the virus but could be a critical treatment if a virus emerges toward evading coronavirus disease 2019 (COVID-19) vaccines. Despite the significant efforts to test already-approved drugs for their potential to kill the virus, researchers found very few actually worked. Methods: The present report uses the electronic molecular descriptors, the quasi-valence number (AQVN), and the electron-ion interaction potential (EIIP), for the analysis of natural compounds with proven therapeutic activity against the COVID-19. Results: Based on the analysis of the electronic properties of natural compounds which are effective against SARS-CoV-2 virus the simple theoretical criterion for the selection of candidate compounds for the treatment of COVID-19 is proposed. Conclusions: The proposed theoretical criterion can be used for the identification and optimization of new lead compounds for the treatment of the COVID-19 disease and for the selection of the food and food supplements which could have a beneficial effect on COVID-19 patients.
... NT-VRL displayed an antiviral impact, which ought to ideally be fixed up with tissue before infection openness (Guerrero-García and Rubio-Guerra 2018). Alveoli are primary sites influenced by COVID protection medication straight forwardly to alveoli, perhaps utilising inward breath, would be the ideal organization course for this possible remedial arrangement (Cinatl et al. 2003). ...
Article
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The human coronavirus disease (COVID-19) pandemic is caused by a novel coronavirus; the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2). Natural products, secondary metabolites show positive leads with antiviral and immunotherapy treatments using genomic studies in silico docking. In addition, it includes the action of a mechanism targeting the SARS-CoV-2. In this literature, we aimed to evaluate the antiviral movement of the NT-VRL-1 unique terpene definition to Human coronavirus (HCoV-229E). The effects of 19 hydrolysable tannins on the SARS-CoV-2 were therefore theoretically reviewed and analyzed utilising the molecular operating surroundings for their C-Like protease 3CLpro catalytic dyad residues Angiotensin converting enzyme-2 (MOE 09). Pedunculagin, tercatan, and castalin were detected as interacting strongly with SARS-receptor Cov-2’s binding site and catalytic dyad (Cys145 and His41). SARS-CoV-2 methods of subunit S1 (ACE2) inhibit the interaction of the receiver with the s-protein once a drug molecule is coupled to the s-protein and prevent it from infecting the target cells in alkaloids. Our review strongly demonstrates the evidence that natural compounds and their derivatives can be used against the human coronavirus and serves as an area of research for future perspective.
... Its mechanism of action is based on inhibiting the viral replication in the host cell. (47) Another in-silico study suggests that glycyrrhiza may be used as a possible replication inhibitor in COVID-19 infection. (48) Glycyrrhiza glabra may be an alternative approach for preventing the COVID-19 infection. ...
Article
To date, no satisfactory treatment for COVID-19 is available. This review reported few recent updates regarding the drugs (allopathy/traditional medicines) used for the treatment of COVID-19 concerning clinical studies. Content of the article spotlight the contribution of allopathic and Ayurvedic drugs to the scientific basis for utilization as a potential therapy against COVID-19 infection and provide new insights on the integration of allopathy and traditional medicine. It advocated the combination of these two systems of treatment will ascertain their integrations, and there would be a good possibility and scope for developing a model of integration in the management of COVID-19. Provided discussion may help researchers, physicians, and healthcare policymakers to encourage for effective and integrated use of allopathic and Ayurvedic medicines to control the COVID-19 pandemic more effectively.
... Consequently, many unrelated RNA viruses are sensitive to ribavirin [55][56][57]. However, ribavirin has no or limited antiviral activity against coronaviruses, including SARS [58][59][60]. The ExoN of CoV NSP14 was shown to excise ribavirin 5 -monophosphate after its incorporation into viral RNA, providing a potential explanation for its limited efficacy in vivo [21]. ...
Article
Full-text available
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the COVID-19 pandemic. While the development of vaccines and the emergence of antiviral therapeutics is promising, alternative strategies to combat COVID-19 (and potential future pandemics) remain an unmet need. Coronaviruses feature a unique mechanism that may present opportunities for therapeutic intervention: the RNA polymerase complex of coronaviruses is distinct in its ability to proofread and remove mismatched nucleotides during genome replication and transcription. The proofreading activity has been linked to the exonuclease (ExoN) activity of non-structural protein 14 (NSP14). Here, we review the role of NSP14, and other NSPs, in SARS-CoV-2 replication and describe the assays that have been developed to assess the ExoN function. We also review the nucleoside analogs and non-nucleoside inhibitors known to interfere with the proofreading activity of NSP14. Although not yet validated, the potential use of non-nucleoside proofreading inhibitors in combination with chain-terminating nucleosides may be a promising avenue for the development of anti-CoV agents.
... In in silico work, it has been shown that terpene Ginkgolide A can strongly inhibit the SARS CoV-2 protease enzyme [12]. In addition, Glycyrrhizin, a triterpene found in licorice roots, could inhibit SARS-CoV replication in vitro [77] and its efficacy was also obtained in patients [78]. Squalene, a natural triterpene which is a precursor of sterols and other bioactive terpenoids, was extracted from pumpkin seed oil. ...
Article
Full-text available
Citation: Brahmi, F.; Vejux, A.; Ghzaiel, I.; Ksila, M.; Zarrouk, A.; Ghrairi, T.; Essadek, S.; Mandard, S.; Leoni, V.; Poli, G.; et al. Role of Diet and Nutrients in SARS-CoV-2
... Herbal medicines and medicinal plant-based natural compounds provide a rich resource for novel antiviral drug development. Some natural medicines have been shown to possess antiviral activities against various virus strains including coronavirus, herpes simplex virus [23][24][25], influenza virus [25], human immunodeficiency virus [26], hepatitis B and C viruses [27], SARS, and MERS [28,29]. These compounds antiviral action mechanisms caused by influencing of the viral life cycle, such as viral entry, replication, assembly, and release, as well as virus-host-specific interactions. ...
Article
Full-text available
COVID-19 is still a global pandemic that has not been stopped. Many traditional medicines have been demonstrated to be incredibly helpful for treating COVID-19 patients while fighting the disease worldwide. We introduced 10 bioactive compounds derived from traditional medicinal plants and assessed their potential for inhibiting viral spike protein (S-protein), Papain-like protease (PLpro), and RNA dependent RNA polymerase (RdRp) using molecular docking protocols where we simulate the inhibitors bound to target proteins in various poses and at different known binding sites using Autodock version 4.0 and Chimera 1.8.1 software. Results found that the chicoric acid, quinine, and withaferin A ligand strongly inhibited CoV-2 S -protein with a binding energy of −8.63, −7.85, and −7.85 kcal/mol, respectively. Our modeling work also suggested that curcumin, quinine, and demothoxycurcumin exhibited high binding affinity toward RdRp with a binding energy of −7.80, −7.80, and −7.64 kcal/mol, respectively. The other ligands, namely chicoric acid, demothoxycurcumin, and curcumin express high binding energy than the other tested ligands docked to PLpro with −7.62, −6.81, and −6.70 kcal/mol, respectively. Prediction of drug-likeness properties revealed that all tested ligands have no violations to Lipinski’s Rule of Five except cepharanthine, chicoric acid, and theaflavin. Regarding the pharmacokinetic behavior, all ligand predicted to have high GI-absorption except chicoric acid and theaflavin. At the same way chicoric acid, withaferin A, and withanolide D predicted to be substrate for multidrug resistance protein (P-gp substrate). Caffeic acid, cepharanthine, chicoric acid, withaferin A, and withanolide D also have no inhibitory effect on any cytochrome P450 enzymes. Promisingly, chicoric acid, quinine, curcumin, and demothoxycurcumin exhibited high binding affinity on SARS-CoV-2 target proteins and expressed good drug-likeness and pharmacokinetic properties. Further research is required to investigate the potential uses of these compounds in the treatment of SARS-CoV-2. View Full-Text
... Apart from chemical drugs, extracts of Ganoderma lucidum (RF3), Perilla frutescens, and Mentha haplocalyx have been found effective against SARS-CoV-2 infection [38]. Glycyrrhizin, a common Chinese herbal medicine, is an efficient and safe natural compound to inhibit SARS-CoV-2 and SARS [42,43], but without target information either. ...
Article
Target prediction and virtual screening are two powerful tools of computer-aided drug design. Target identification is of great significance for hit discovery, lead optimization, drug repurposing and elucidation of the mechanism. Virtual screening can improve the hit rate of drug screening to shorten the cycle of drug discovery and development. Therefore, target prediction and virtual screening are of great importance for developing highly effective drugs against COVID-19. Here we present D3AI-CoV, a platform for target prediction and virtual screening for the discovery of anti-COVID-19 drugs. The platform is composed of three newly developed deep learning-based models i.e., MultiDTI, MPNNs-CNN and MPNNs-CNN-R models. To compare the predictive performance of D3AI-CoV with other methods, an external test set, named Test-78, was prepared, which consists of 39 newly published independent active compounds and 39 inactive compounds from DrugBank. For target prediction, the areas under the receiver operating characteristic curves (AUCs) of MultiDTI and MPNNs-CNN models are 0.93 and 0.91, respectively, whereas the AUCs of the other reported approaches range from 0.51 to 0.74. For virtual screening, the hit rate of D3AI-CoV is also better than other methods. D3AI-CoV is available for free as a web application at http://www.d3pharma.com/D3Targets-2019-nCoV/D3AI-CoV/index.php, which can serve as a rapid online tool for predicting potential targets for active compounds and for identifying active molecules against a specific target protein for COVID-19 treatment.
... Herbal medicines and medicinal plant-based natural compounds provide a rich resource for novel antiviral drug development. Some natural medicines have been shown to possess antiviral activities against various virus strains including coronavirus, herpes simplex virus [23][24][25], influenza virus [25], human immunodeficiency virus [26], hepatitis B and C viruses [27], SARS, and MERS [28,29]. These compounds antiviral action mechanisms caused by influencing of the viral life cycle, such as viral entry, replication, assembly, and release, as well as virus-host-specific interactions. ...
... Herbal medicines and medicinal plant-based natural compounds provide a rich resource for novel antiviral drug development. Some natural medicines have been shown to possess antiviral activities against various virus strains including coronavirus, herpes simplex virus [23][24][25], influenza virus [25], human immunodeficiency virus [26], hepatitis B and C viruses [27], SARS, and MERS [28,29]. These compounds antiviral action mechanisms caused by influencing of the viral life cycle, such as viral entry, replication, assembly, and release, as well as virus-host-specific interactions. ...
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... In many countries of Europe, doctors have been recommending Ayurvedic medicine to patients along with allopathic medicines. Glycyrrhizin, glycyrrhizic acid (GLR) an active component of liquorice roots, also a good candidate to be tested against the SARS-CoV-2 corona virus, alone and in combination with other drugs can also be further considered and rapidly evaluated for the treatment of patients with COVID-19 [53,54]. ...
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... However, since the study used a concentration of GL that is not physiologically relevant, it is believed that further validation is required. Another research assessed the antiviral potential against two clinical isolates of coronavirus (FFM-1 and FFM-2) and found that 4000 lg/mL of GL completely inhibited the virus replication in Vero cells, especially showing high inhibitory efficacy when treated during the adsorption and penetration steps (Cinatl et al., 2003). In addition, Matsumoto et al. confirmed that GL can interfere in the release step of HCV (Matsumoto et al., 2013). ...
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