Effect of andrographolide and deep eutectic solvent extracts of Andrographis paniculata on human coronavirus organ culture 43 (HCoV-OC43).

BACKGROUND: Andrographis paniculata (Burm. f.) Nees has demonstrated potential for treating infections caused by coronaviruses. However, no antiviral activity of andrographolide or A. paniculata extracts against human coronavirus organ culture 43 (HCoV-OC43) has been reported. PURPOSE: This study aimed to evaluate the anti-HCoV-OC43 effect of andrographolide and A. paniculata as well as the correlation between andrographolide concentration and the anti-HCoV-OC43 activity of A. paniculata extracts. METHODS: This study evaluated and compared the in vitro anti-HCoV-OC43 activities of various A. paniculata extracts and andrographolide. To obtain A. paniculata extracts with different concentrations of andrographolide and its components, methanol and deep eutectic solvents (DES) were used to extract the aerial parts of A. paniculata. Andrographolide content was determined using UV-HPLC, and antiviral activity was assessed in HCT-8 colon cells. RESULTS: The methanol and five acidic DES (containing malic acid or citric acid) extracts of A. paniculata exerted anti-HCoV-OC43 activity. Antiviral activity had a moderately strong positive linear relationship (r = 0.7938) with andrographolide content. Although the methanol extract contained the highest andrographolide content (2.34 mg/ml), its anti-HCoV-OC43 activity was lower than that of the DES extracts containing lower andrographolide concentrations (0.92-1.46 mg/ml). CONCLUSION: Methanol and the five acidic DES extracts of A. paniculata exhibited anti-HCoV-OC43 activity. However, the in vitro antiviral activity of A. paniculata extracts did not have a very strong positive linear relationship (r < 0.8) with andrographolide concentration in the extract. As a result, when comparing A. paniculata extracts, the anti-HCoV-OC43 test could provide a different result from the andrographolide concentration determination.

Therapeutically important bioactive compounds of the genus Polygonum L. and their possible interventions in clinical medicine.

OBJECTIVES: Increasing literature data have suggested that the genus Polygonum L. possesses pharmacologically important plant secondary metabolites. These bioactive compounds are implicated as effective agents in preclinical and clinical practice due to their pharmacological effects such as anti-inflammatory, anticancer, antidiabetic, antiaging, neuroprotective or immunomodulatory properties among many others. However, elaborate pharmacological and clinical data concerning the bioavailability, tissue distribution pattern, dosage and pharmacokinetic profiles of these compounds are still scanty. KEY FINDINGS: The major bioactive compounds implicated in the therapeutic effects of Polygonum genus include phenolic and flavonoid compounds, anthraquinones and stilbenes, such as quercetin, resveratrol, polydatin and others, and could serve as potential drug leads or as adjuvant agents. Data from in-silico network pharmacology and computational molecular docking studies are also highly helpful in identifying the possible drug target of pathogens or host cell machinery. SUMMARY: We provide an up-to-date overview of the data from pharmacodynamic, pharmacokinetic profiles and preclinical (in-vitro and in-vivo) investigations and the available clinical data on some of the therapeutically important compounds of genus Polygonum L. and their medical interventions, including combating the outbreak of the COVID-19 pandemic.

Antiviral activity of berberine.

Plants are a rich source of new antiviral, pharmacologically active agents. The naturally occurring plant alkaloid berberine (BBR) is one of the phytochemicals with a broad range of biological activity, including anticancer, anti-inflammatory and antiviral activity. BBR targets different steps in the viral life cycle and is thus a good candidate for use in novel antiviral drugs and therapies. It has been shown that BBR reduces virus replication and targets specific interactions between the virus and its host. BBR intercalates into DNA and inhibits DNA synthesis and reverse transcriptase activity. It inhibits replication of herpes simplex virus (HSV), human cytomegalovirus (HCMV), human papillomavirus (HPV), and human immunodeficiency virus (HIV). This isoquinoline alkaloid has the ability to regulate the MEK-ERK, AMPK/mTOR, and NF-κB signaling pathways, which are necessary for viral replication. Furthermore, it has been reported that BBR supports the host immune response, thus leading to viral clearance. In this short review, we focus on the most recent studies on the antiviral properties of berberine and its derivatives, which might be promising agents to be considered in future studies in the fight against the current pandemic SARS-CoV-2, the virus that causes COVID-19.

Effect of herbal compounds on coronavirus; a systematic review and meta-analysis.

BACKGROUND: The new coronavirus (COVID-19) has been transmitted exponentially. Numerous studies have been performed in recent years that have shown the inhibitory effect of plant extracts or plant-derived compounds on the coronavirus family. In this study, we want to use systematic review and meta-analysis to answer the question, which herbal compound has been more effective? MAIN BODY: The present study is based on the guidelines for conducting meta-analyzes. An extensive search was conducted in the electronic database, and based on the inclusion and exclusion criteria, articles were selected and data screening was done. Quality control of articles was performed. Data analysis was carried out in STATA software. CONCLUSION: Due to the variety of study methods, definitive conclusions are not possible. However, in this study, we attempted to gather all the available evidence on the effect of plant compounds on SARS-COV-2 to be used for the development and use of promising antiviral agents against this virus and other coronaviruses. Trypthantrin, Sambucus extract, S. cusia extract, Boceprevir and Indigole B, dioica agglutinin urtica had a good effect on reducing the virus titer. Also among the compounds that had the greatest effect on virus inhibition, Saikosaponins B2, SaikosaponinsD, SaikosaponinsA and Phillyrin, had an acceptable selectivity index greater than 10. Andrographolide showed the highest selectivity index on SARS-COV-2. Our study confirmed insufficient data to support alkaloid compounds against SARS-COV-2, and the small number of studies that used alkaloid compounds was a limitation. It is recommended to investigate the effect of more alkaloid compounds against Corona virus.

Phillyrin (KD-1) exerts anti-viral and anti-inflammatory activities against novel coronavirus (SARS-CoV-2) and human coronavirus 229E (HCoV-229E) by suppressing the nuclear factor kappa B (NF-κB) signaling pathway.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has extensively and rapidly spread in the world, causing an outbreak of acute infectious pneumonia. However, no specific antiviral drugs or vaccines can be used. Phillyrin (KD-1), a representative ingredient of Forsythia suspensa, possesses anti-inflammatory, anti-oxidant, and antiviral activities. However, little is known about the antiviral abilities and mechanism of KD-1 against SARS-CoV-2 and human coronavirus 229E (HCoV-229E). PURPOSE: The study was designed to investigate the antiviral and anti-inflammatory activities of KD-1 against the novel SARS-CoV-2 and HCoV-229E and its potential effect in regulating host immune response in vitro. METHODS: The antiviral activities of KD-1 against SARS-CoV-2 and HCoV-229E were assessed in Vero E6 cells using cytopathic effect and plaque-reduction assay. Proinflammatory cytokine expression levels upon infection with SARS-CoV-2 and HCoV-229E infection in Huh-7 cells were measured by real-time quantitative PCR assays. Western blot assay was used to determine the protein expression of nuclear factor kappa B (NF-κB) p65, p-NF-κB p65, IκBα, and p-IκBα in Huh-7 cells, which are the key targets of the NF-κB pathway. RESULTS: KD-1 could significantly inhibit SARS-CoV-2 and HCoV-229E replication in vitro. KD-1 could also markedly reduce the production of proinflammatory cytokines (TNF-α, IL-6, IL-1ß, MCP-1, and IP-10) at the mRNA levels. Moreover, KD-1 could significantly reduce the protein expression of p-NF-κB p65, NF-κB p65, and p-IκBα, while increasing the expression of IκBα in Huh-7 cells. CONCLUSIONS: KD-1 could significantly inhibit virus proliferation in vitro, the up-regulated expression of proinflammatory cytokines induced by SARS-CoV-2 and HCoV-229E by regulating the activity of the NF-кB signaling pathway. Our findings indicated that KD-1 protected against virus attack and can thus be used as a novel strategy for controlling the coronavirus disease 2019.

Unravelling lead antiviral phytochemicals for the inhibition of SARS-CoV-2 Mpro enzyme through in silico approach.

A new SARS coronavirus (SARS-CoV-2) belonging to the genus Betacoronavirus has caused a pandemic known as COVID-19. Among coronaviruses, the main protease (Mpro) is an essential drug target which, along with papain-like proteases catalyzes the processing of polyproteins translated from viral RNA and recognizes specific cleavage sites. There are no human proteases with similar cleavage specificity and therefore, inhibitors are highly likely to be nontoxic. Therefore, targeting the SARS-CoV-2 Mpro enzyme with small molecules can block viral replication. The present study is aimed at the identification of promising lead molecules for SARS-CoV-2 Mpro enzyme through virtual screening of antiviral compounds from plants. The binding affinity of selected small drug-like molecules to SARS-CoV-2 Mpro, SARS-CoV Mpro and MERS-CoV Mpro were studied using molecular docking. Bonducellpin D was identified as the best lead molecule which shows higher binding affinity (-9.28 kcal/mol) as compared to the control (-8.24 kcal/mol). The molecular binding was stabilized through four hydrogen bonds with Glu166 and Thr190 as well as hydrophobic interactions via eight residues. The SARS-CoV-2 Mpro shows identities of 96.08% and 50.65% to that of SARS-CoV Mpro and MERS-CoV Mpro respectively at the sequence level. At the structural level, the root mean square deviation (RMSD) between SARS-CoV-2 Mpro and SARS-CoV Mpro was found to be 0.517 Å and 0.817 Å between SARS-CoV-2 Mpro and MERS-CoV Mpro. Bonducellpin D exhibited broad-spectrum inhibition potential against SARS-CoV Mpro and MERS-CoV Mpro and therefore is a promising drug candidate, which needs further validations through in vitro and in vivo studies.

The Biosynthesized Zinc Oxide Nanoparticles' Antiviral Activity in Combination with Pelargonium zonale Extract against the Human Corona 229E Virus.

Almost one-third of all infectious diseases are caused by viruses, and these diseases account for nearly 20% of all deaths globally. It is becoming increasingly clear that highly contagious viral infections pose a significant threat to global health and economy around the world. The need for innovative, affordable, and safe antiviral therapies is a must. Zinc oxide nanoparticles are novel materials of low toxicity and low cost and are known for their antiviral activity. The genus Pelargonium was previously reported for its antiviral and antimicrobial activity. In this work, Pelargonium zonale leaf extract chemical profile was studied via high-performance liquid chromatography (HPLC) and was used for the biosynthesis of zinc oxide nanoparticles. Furthermore, the antiviral activity of the combination of P. zonale extract and the biosynthesized nanoparticles of ZnO against the human corona 229E virus was investigated. Results revealed that ZnONPs had been biosynthesized with an average particle size of about 5.5 nm and characterized with UV, FTIR, TEM, XRD, and SEM. The antiviral activity showed significant activity and differences among the tested samples in favor of the combination of P. zonale extract and ZnONPs (ZnONPs/Ex). The lowest IC50, 2.028 µg/mL, and the highest SI, 68.4 of ZnONPs/Ex, assert the highest antiviral activity of the combination against human coronavirus (229E).

Anti-otomycotic potential of nanoparticles of Moringa oleifera leaf extract: an integrated in vitro, in silico and phase 0 clinical study.

Otomycosis is a serious superficial mycotic infection of the outer ear canal caused by some pathogenic species of Candida and Aspergillus. The infection remains a challenge to clinicians owing to the incomplete efficacy of market-available antifungal agents and high recurrence rates. The Moringa oleifera leaf ethanol extract showed efficacy against Candida albicans SC5314, compared to Nystatin® as a reference with MIC values of 7 and 718.33 µg ml-1, respectively. The extract was mixed with lecithin and chitosan to give Moringa core/shell giant nanoparticles, with a good zeta potential (+59.2 mV), a suitable entrapment efficiency (61%) and an enhanced release reaching up to 90% at 8 h. Clinical isolates from oomycote patients were identified via DNA sequencing as Candida parapsilosis, Aspergillus niger and Aspergillus flavus, and the effect of the prepared nanoparticles was tested against them via disk diffusion assay to give inhibition zones of 75, 55 and 55 mm, compared to Nystatin® with 35, 25 and 20 mm, respectively. Interestingly, patients treated with the Moringa-loaded nanoparticles experienced improvement within 1 week with no recurrence for more than 3 months. To have some insight into the bioactive components in the Moringa extract, LC-HRMS-based identification has been employed which led to the annotation of 27 compounds. Subsequent comprehensive in silico investigation suggested some alkaloids to be responsible for the activity targeting the fungal 14-α-demethylase enzyme (CYP51B). Our study revealed that Moringa extract-loaded nanoparticles attained an enhanced antifungal efficacy compared to Nystatin® and therefore they can be employed against invasive and drug-resistant otomycotic infections.

Antiviral COVID-19 protein and molecular docking: In silico characterization of various antiviral compounds extracted from Arisaema jacquemontii Blume.

Arisaema jacquemontii Blume is a highly medicinal and poisonous plant belong to the family Araceae. It is used to treat several deadly diseases, including viral infections. It has antioxidant, anti-cancerous, antimalarial, anti-vermicidal, and antiviral activities. Therefore, five parts of the Arisaema jacquemontii Blume plant, such as leaf, seed, stem, pulp, and rhizome extract, were evaluated for metabolic and in silico characterization of probable compounds using gas chromatography-mass spectrometry (GC-MS) analysis. A total of 22 compounds were isolated from the methanolic extracts of A. jacquemontii Blume. A selected antiviral COVID-19 protein i.e., protease (6LU7) was docked against the obtained compounds. Different affinities were obtained through various compounds. The best results were shown by three different compounds identified in the rhizome. The maximum binding affinity of these compounds is 8.1 kJ/mol. Molecular docking (MD) indicate that these molecules have the highest binding energies and hydrogen bonding interactions. The binding mode of interaction was discovered to be reasonably effective for counteracting the SARS virus COVID-19. The findings of this study could be extremely useful in the development of more phytochemical-based COVID-19 therapeutics.

Alleviation of Post-COVID-19 Cognitive Deficits by Treatment with EGb 761®: A Case Series.

BACKGROUND Cognitive symptoms persisting longer than 3 months after infection, such as memory loss, or difficulties concentrating, have been reported in up to one-third of patients after COVID-19. Evidence-based therapeutic interventions to treat post-COVID-19 symptoms (also called "Long-COVID symptoms") have not yet been established, and the treating physicians must rely on conjecture to help patients. Based on its mechanism of action and its efficacy in treating cognitive impairment, as well as its good tolerability, the Ginkgo biloba special extract EGb 761 has been suggested as a remedy to alleviate cognitive post-COVID-19 symptoms. In many studies, EGb 761 has been demonstrated to protect endothelial cells, to have potent anti-inflammatory effects, and to enhance neuroplasticity. CASE REPORT Here, we report for the first time the application of EGb 761 in the therapy of post-COVID-19-related cognitive deficits. Three women and 2 men, aged 26 to 59 years (average age 34.6 years), presented with concentration and attention deficits, cognitive deficiencies, and/or fatigue 9-35 weeks after infection. A daily dose of 2×80 mg of EGb 761 did not cause any detectable adverse effects, and it substantially improved or completely restored cognitive deficits and, when initially present, also other symptoms, such as fatigue and hyposmia, within an observation period of up to 6 months. CONCLUSIONS Our observations support the hypothesis that EGb 761 might be a low-risk treatment option for post-COVID-19 patients with cognitive symptoms. Moreover, we derive recommendations for randomized controlled clinical trials to confirm efficacy in that indication.

Barbaloin: an amazing chemical from the 'wonder plant' with multidimensional pharmacological attributes.

Aloe vera (L.) Burm.f. is nicknamed the 'Miracle plant' or sometimes as the 'Wonder plant'. It is a plant that has been used since ancient times for the innumerable health benefits associated with it. It is one of the important plants that has its use in conventional medicinal treatments. It is a perennial succulent, drought-tolerant member of the family Asphodelaceae. There are scores of properties associated with the plant that help in curing various forms of human ailments. Extracts and gels obtained from plants have been shown to be wonderful healers of different conditions, mainly various skin problems. Also, this plant is popular in the cosmetics industry. The underlying properties of the plant are now mainly associated with the natural phytochemicals present in the plant. Diverse groups of phytoingredients are found in the plant, including various phenolics, amino acids, sugars, vitamins, and different other organic compounds, too. One of the primary ingredients found in the plant is the aloin molecule. It is an anthraquinone derivative and exists as an isomer of Aloin A and Aloin B. Barbaloin belonging to the first group is a glucoside of the aloe-emodin anthrone molecule. Various types of pharmacological properties exhibited by the plant can be attributed to this chemical. Few significant ones are antioxidant, anti-inflammatory, anti-diabetic, anti-cancer, anti-microbial, and anti-viral, along with their different immunity-boosting actions. Recently, molecular coupling studies have also found the role of these molecules as a potential cure against the ongoing COVID-19 disease. This study comprehensively focuses on the numerous pharmacological actions of the primary compound barbaloin obtained from the Aloe vera plant along with the mechanism of action and the potent application of these natural molecules under various conditions.

High-CBD Extract (CBD-X) Downregulates Cytokine Storm Systemically and Locally in Inflamed Lungs.

Cytokine storm refers to the dysregulated production of inflammatory mediators leading to hyperinflammation. They are often detrimental, and worsen the severity of COVID-19 and other infectious or inflammatory diseases. Cannabinoids are known to have anti-inflammatory effects but their possible therapeutic value on cytokine storms has not been fully elucidated. In vivo and ex vivo studies were carried out to investigate the effects of high-THC and high-CBD extracts on cytokine production in immune cells. Significant differences between the extracts were observed. Subsequent experiments focusing on a specific high CBD extract (CBD-X) showed significant reductions in pro-inflammatory cytokines in human-derived PBMCs, neutrophils and T cells. In vivo mouse studies, using a systemically inflamed mouse model, showed reductions in pro-inflammatory cytokines TNFα and IL-1ß and a concurrent increase in the anti-inflammatory cytokine IL-10 in response to CBD-X extract treatment. Lung inflammation, as in severe COVID-19 disease, is characterized by increased T-cell homing to the lungs. Our investigation revealed that CBD-X extract impaired T-cell migration induced by the chemoattractant SDF1. In addition, the phosphorylation levels of T cell receptor (TCR) signaling proteins Lck and Zap70 were significantly reduced, demonstrating an inhibitory effect on the early events downstream to TCR activation. In a lung inflamed mouse model, we observed a reduction in leukocytes including neutrophil migration to the lungs and decreased levels of IL-1ß, MCP-1, IL-6 and TNFα, in response to the administration of the high-CBD extract. The results presented in this work offer that certain high-CBD extract has a high potential in the management of pathological conditions, in which the secretion of cytokines is dysregulated, as it is in severe COVID-19 disease or other infectious or inflammatory diseases.

Artemisia Extracts and Artemisinin-Based Antimalarials for COVID-19 Management: Could These Be Effective Antivirals for COVID-19 Treatment?

As the world desperately searches for ways to treat the coronavirus disease 2019 (COVID-19) pandemic, a growing number of people are turning to herbal remedies. The Artemisia species, such as A. annua and A. afra, in particular, exhibit positive effects against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and COVID-19 related symptoms. A. annua is a source of artemisinin, which is active against malaria, and also exhibits potential for other diseases. This has increased interest in artemisinin's potential for drug repurposing. Artemisinin-based combination therapies, so-called ACTs, have already been recognized as first-line treatments against malaria. Artemisia extract, as well as ACTs, have demonstrated inhibition of SARS-CoV-2. Artemisinin and its derivatives have also shown anti-inflammatory effects, including inhibition of interleukin-6 (IL-6) that plays a key role in the development of severe COVID-19. There is now sufficient evidence in the literature to suggest the effectiveness of Artemisia, its constituents and/or artemisinin derivatives, to fight against the SARS-CoV-2 infection by inhibiting its invasion, and replication, as well as reducing oxidative stress and inflammation, and mitigating lung damage.

The Extracts of Polygonum cuspidatum Root and Rhizome Block the Entry of SARS-CoV-2 Wild-Type and Omicron Pseudotyped Viruses via Inhibition of the S-Protein and 3CL Protease.

COVID-19, resulting from infection by the SARS-CoV-2 virus, caused a contagious pandemic. Even with the current vaccines, there is still an urgent need to develop effective pharmacological treatments against this deadly disease. Here, we show that the water and ethanol extracts of the root and rhizome of Polygonum cuspidatum (Polygoni Cuspidati Rhizoma et Radix), a common Chinese herbal medicine, blocked the entry of wild-type and the omicron variant of the SARS-CoV-2 pseudotyped virus into fibroblasts or zebrafish larvae, with IC50 values ranging from 0.015 to 0.04 mg/mL. The extracts were shown to inhibit various aspects of the pseudovirus entry, including the interaction between the spike protein (S-protein) and the angiotensin-converting enzyme II (ACE2) receptor, and the 3CL protease activity. Out of the chemical compounds tested in this report, gallic acid, a phytochemical in P. cuspidatum, was shown to have a significant anti-viral effect. Therefore, this might be responsible, at least in part, for the anti-viral efficacy of the herbal extract. Together, our data suggest that the extracts of P. cuspidatum inhibit the entry of wild-type and the omicron variant of SARS-CoV-2, and so they could be considered as potent treatments against COVID-19.

A Possible Synergistic Herbal Solution for COVID-19.

The COVID-19 pandemic has provided an opportunity for repurposing of drugs, including complex, natural drugs, to meet the global need for safe and effective antiviral medicines which do not promote multidrug resistance nor inflate medical costs. The author herein describes his own repurposing of herbal tinctures, previously prepared for oncology, into a possibly synergistic, anti-COVID 41 "herb" formula of extracts derived from 36 different plants and medicinal mushrooms. A method of multi-sample in vitro testing in green monkey kidney vero cells is proposed for testing the Hypothesis that even in such a large combination, antiviral potency may be preserved, along with therapeutic synergy, smoothness, and complexity. The possibility that the formula's potency may improve with age is considered, along with a suitable method for testing it. Collaborative research inquiries are welcome.

Orobanche crenata Forssk. Extract Affects Human Breast Cancer Cell MCF-7 Survival and Viral Replication.

BACKGROUND: Breast cancer (BC) is the leading cause of death worldwide. The severity of BC strictly depends on the molecular subtype. The less aggressive hormone-positive subtype is treated with adjuvant endocrine therapy (AET), which causes both physical and psychological side effects. This condition strongly impacts the adherence and persistence of AET among oncologic patients. Moreover, viral infections also constitute a serious problem for public health. Despite their efficacy, antiviral agents present several therapeutic limits. Accordingly, in the present work, we investigated the antitumor and antiviral activities of Orobanche crenata Forssk. (O. crenata), a parasitic plant, endemic to the Mediterranean basin, traditionally known for its beneficial properties for human health. METHODS: The MTT assay was carried out to evaluate the cytotoxic effect of O. crenata leaf extract (OCLE) on human breast cancer cells (MCF-7 and MDA-MB-231) and the primary HFF-1 cell line. The lactic dehydrogenase (LDH) assay was performed on MCF-7 cells to analyze necrotic cell death. The antioxidant effect of OCLE was evaluated by intracellular determination of the reactive oxygen species and thiol groups, by DPPH and ABTS assays. The antiviral activity of OCLE was determined against Poliovirus 1, Echovirus 9, Human respiratory syncytial virus, Adenovirus type 2 and type 5, Coxsackievirus B1 (CoxB1) and B3 (CoxB3), Herpes simplex type 1 (HSV-1) and type 2 (HSV-2), and ß-Coronavirus by the plaque reduction assay. RESULTS: The extract, after 24 h of incubation, did not affect MDA-MB-231 and HFF-1 cell viability. However, at the same time point, it showed a dose-dependent inhibitory effect on MCF-7 cells, with an increase in LDH release. OCLE exhibited free radical scavenging activity and significantly increased non-protein thiol levels in MCF-7 cells. OCLE effectively inhibited HSV-1, HSV-2, CoxB1, and CoxB3 replication. CONCLUSIONS: The overall results showed an interesting inhibitory effect of OCLE on both MCF-7 cell survival and viral replication.

Quinic and Digallic acids from Pistacia atlantica Desf. Leaves Extracts as Potent Dual Effect Inhibitors against main Protease and RNA-dependent RNA Polymerase of SARS-CoV-2.

BACKGROUND: Through this study, the Chemical composition realized by UHPLC-DADESI- MSn allowed the detection of different phenolic compound groups from Pistacia atlantica Desf. leaves extracts. We studied the inhibition of main protease (CL3 Mpro) and RNA-dependent RNA polymerase (RdRp) of the SARS-CoV-2 by the identified molecules through molecular docking. OBJECTIVE: The objective of this study is to identify compounds from Pistacia atlantica Desf. leaves extracts, which might have anti-viral effects. METHODS: Chemical composition was realized by UHPLC-DAD-ESI-MSn, and the inhibition of the main protease (CL3 Mpro) and RNA-dependent RNA polymerase (RdRp) of the SARS-CoV-2 was studied using molecular docking with Autodock Vina software. ADMET analysis was carried out. RESULTS: The identified compounds are quinic acid, digallic acid, galloylquinic acid, gallic acid, trigallic acid, digalloylquinic acids, trigalloylquinic acids and methyl gallate; digallic and quinic acids are the best inhibitors. Digallic acid had binding affinity energy (BAE) of -8.2 kcal/mol, and Ki of 1µM for the CL3 Mpro, Ki of 0.62 mM for the RdRp. Quinic acid showed Ki of 4.6 mM, recorded for both enzymes. Through ADMET analysis, we have found that the two molecules are good drug candidates. CONCLUSION: This is the first time that a group of identified compounds from Pistacia atlantica Desf. leaves are studied for their potential activity against the novel virus by inhibiting two key enzymes in its life cycle, and no further studies have been published in this context.

Ginkgo biloba in the management of the COVID-19 severity.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is linked with inflammatory disorders and the development of oxidative stress in extreme cases. Therefore, anti-inflammatory and antioxidant drugs may alleviate these complications. Ginkgo biloba L. folium extract (EGb) is a herbal medicine containing various active constituents. This review aims to provide a critical discussion on the potential role of EGb in the management of coronavirus disease 2019 (COVID-19). The antiviral effect of EGb is mediated by different mechanisms, including blocking SARS-CoV-2 3-chymotrypsin-like protease that provides trans-variant effectiveness. Moreover, EGb impedes the development of pulmonary inflammatory disorders through the diminution of neutrophil elastase activity, the release of proinflammatory cytokines, platelet aggregation, and thrombosis. Thus, EGb can attenuate the acute lung injury and acute respiratory distress syndrome in COVID-19. In conclusion, EGb offers the potential of being used as adjuvant antiviral and symptomatic therapy. Nanosystems enabling targeted delivery, personalization, and booster of effects provide the opportunity for the use of EGb in modern phytotherapy.

Use of hyphenated analytical techniques to identify the bioactive constituents of Gunnera perpensa L., a South African medicinal plant, which potently inhibit SARS-CoV-2 spike glycoprotein-host ACE2 binding.

SARS-CoV-2, the causative agent of COVID-19, continues to cause global morbidity and mortality despite the increasing availability of vaccines. Alongside vaccines, antivirals are urgently needed to combat SARS-CoV-2 infection and spread, particularly in resource-limited regions which lack access to existing therapeutics. Small molecules isolated from medicinal plants may be able to block cellular entry by SARS-CoV-2 by antagonising the interaction of the viral spike glycoprotein receptor-binding domain (RBD) with the host angiotensin-converting enzyme II (ACE2) receptor. As the medicinal plant Gunnera perpensa L. is being used by some South African traditional healers for SARS-CoV-2/COVID-19 management, we hypothesised that it may contain chemical constituents that inhibit the RBD-ACE2 interaction. Using a previously described AlphaScreen-based protein interaction assay, we show here that the DCM:MeOH extract of G. perpensa readily disrupts RBD (USA-WA1/2020)-ACE2 interactions with a half-maximal inhibition concentration (IC50) of < 0.001 µg/mL, compared to an IC50 of 0.025 µg/mL for the control neutralising antibody REGN10987. Employing hyphenated analytical techniques like UPLC-IMS-HRMS (method developed and validated as per the International Conference on Harmonization guidelines), we identified two ellagitannins, punicalin (2.12% w/w) and punicalagin (1.51% w/w), as plant constituents in the DCM:MeOH extract of G. perpensa which antagonised RBD-ACE2 binding with respective IC50s of 9 and 29 nM. This good potency makes both compounds promising leads for development of future entry-based SARS-CoV-2 antivirals. The results also highlight the advantages of combining reverse pharmacology (based on medicinal plant use) with hyphenated analytical techniques to expedite identification of urgently needed antivirals.

Rational and Safe Use of the Top Two Botanical Dietary Supplements to Enhance the Immune System.

The recent COVID-19 pandemic has sparked great interest in strengthening the immune system, especially by the consumption of widely available natural dietary supplements. Because of this popularity, it was suggested that the sales of these products would grow significantly in the year 2021, especially for those who are unable or unwilling to receive COVID-19 vaccines. Among the many botanicals, Sambucus nigra L. (Elderberry) and Echinacea purpurea (L.) Moench (Echinacea) have especially shown great popularity. Various in vivo and in vitro tests of S. nigra and E. purpurea extracts and constituents have confirmed the botanicals' influence on proinflammatory cytokines, viral infections, and flu symptoms, proving their immunomodulatory and antiviral effects. Although there have been promising results with S. nigra and E. purpurea containing supplements, thorough monitoring of the sanitary production, demand, and related side effects after consumption is required. Further research and development of the supplements in accordance with the pandemic are also advised.