Rapid Virucidal Activity of Japanese Saxifraga Species-Derived Condensed Tannins against SARS-CoV-2, Influenza A Virus, and Human Norovirus Surrogate Viruses.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A virus (IAV), and norovirus are global threats to human health. The application of effective virucidal agents, which contribute to the inactivation of viruses on hands and environmental surfaces, is important to facilitate robust virus infection control measures. Naturally derived virucidal disinfectants have attracted attention owing to their safety and eco-friendly properties. In this study, we showed that multiple Japanese Saxifraga species-derived fractions demonstrated rapid, potent virucidal activity against the SARS-CoV-2 ancestral strain and multiple variant strains, IAV, and two human norovirus surrogates: feline calicivirus (FCV) and murine norovirus (MNV). Condensed tannins were identified as active chemical constituents that play a central role in the virucidal activities of these fractions. At a concentration of 25 µg/mL, the purified condensed tannin fraction Sst-2R induced significant reductions in the viral titers of the SARS-CoV-2 ancestral strain, IAV, and FCV (reductions of ≥3.13, ≥3.00, and 2.50 log10 50% tissue culture infective doses [TCID50]/mL, respectively) within 10 s of reaction time. Furthermore, at a concentration of 100 µg/mL, Sst-2R induced a reduction of 1.75 log10 TCID50/mL in the viral titers of MNV within 1 min. Western blotting and transmission electron microscopy analyses revealed that Sst-2R produced structural abnormalities in viral structural proteins and envelopes, resulting in the destruction of viral particles. Furthermore, Saxifraga species-derived fraction-containing cream showed virucidal activity against multiple viruses within 10 min. Our findings indicate that Saxifraga species-derived fractions containing condensed tannins can be used as disinfectants against multiple viruses on hands and environmental surfaces. IMPORTANCE SARS-CoV-2, IAV, and norovirus are highly contagious pathogens. The use of naturally derived components as novel virucidal/antiviral agents is currently attracting attention. We showed that fractions from extracts of Saxifraga species, in the form of a solution as well as a cream, exerted potent, rapid virucidal activities against SARS-CoV-2, IAV, and surrogates of human norovirus. Condensed tannins were found to play a central role in this activity. The in vitro cytotoxicity of the purified condensed tannin fraction at a concentration that exhibited some extent of virucidal activity was lower than that of 70% ethanol or 2,000 ppm sodium hypochlorite solution, which are popular virucidal disinfectants. Our study suggests that Saxifraga species-derived fractions containing condensed tannins can be used on hands and environmental surfaces as safe virucidal agents against multiple viruses.

Screening of Natural Antivirals Against the COVID-19 Pandemic-A Compilation of Updates

Coronavirus disease 2019 (COVID-19), named by WHO, is a real public health disaster of the third millennium. This highly contagious viral disease has infected the world population and is now a global pandemic. This acute respiratory distress syndrome (ARDS) has severe complica-tions like pneumonitis, respiratory failure, shock, multiorgan failure, and death. Well-defined FDA-approved synthetic is not yet available. Case management strategies like lockdown, use of masks and sanitizers, social distancing, and repurposing of antiviral drugs were initially undertaken to cope with this pandemic. Different broad-spectrum antiviral drugs are being repurposed as one of the treatment modalities. The global vaccination programme with the newly launched COVID-19 vac-cines, Covishield, covaxin, sputnik V, etc., is an ongoing process. Simultaneously, significant research is being carried out in search of natural antivirals and evaluating the potency of food bioac-tives to aid naturistic protection against the coronavirus. This mini-review has compiled the latest updates on the screening and evidence-based mechanistic evaluation of phytochemicals and food bioactives as non-pharmacological adjuvant aid in COVID pandemics.Copyright © 2023 Bentham Science Publishers.

Virtual Screening of Potential Therapeutic Inhibitors Against Spike, Heli-case, and Polymerase of SARS-CoV-2 (COVID-19)

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected around 13 million people and has caused more than 5.7 lakh deaths worldwide since December 2019. In the absence of FDA approved drugs for its treatment, only symptomatic management is done. Method(s): We attempted to uncover potential therapeutic targets of spike, helicase, and RNA dependent RNA polymerase (RdRp) proteins of the SARS-CoV-2 employing a computational approach. The PDB structure of spike and RdRp and predicted structure of helicase proteins were docked with 100 approved anti-viral drugs, natural compounds, and some other chemical compounds. Result(s): The anti-SARS ligands EK1 and CID 23631927, and NCGC00029283 are potential entry in-hibitors as they showed affinity with immunogenic Receptor Binding Domain (RBD) of the spike pro-tein. This RBD interacts with Angiotensin Converting Enzyme (ACE2) receptor, facilitating the entry of virion in the host cells. The FDA approved drugs, including Nelfinavir, Saquinavir, Tipranavir, Setrobu-vir, Indinavir, and Atazanavir, showed potential inhibitory activity against targeted domains and thus, may act as entry or replication inhibitor or both. Furthermore, several anti-HCoV natural compounds, including Amentoflavone, Rutin, and Tannin, are also potential entry and replication inhibitors as they showed affinity with RBD, P-loop containing nucleoside triphosphate hydrolase, and the catalytic domain of the respective protein. Dithymoquinone showed significant inhibitory potential against the fusion peptide of S2 domain. Importantly, Tannin, Dithymoquinone, and Rutin can be extracted from Nig-ella sativa seeds and thus, may prove to be one of the most potential anti-SARS-CoV-2 inhibitors. Conclusion(s): Several potential ligands were identified with already known anti-HCoVs activities. Fur-thermore, as this study showed that some of the ligands acted as both entry and replication inhibitors against SARS-CoV-2, it is envisaged that a combination of either inhibitor with a dual mode of action would prove to be a much desired therapeutic option against this viral infection.Copyright © 2021 Bentham Science Publishers.

Bioavailability of iron and its potential to improve the immune system and ward off COVID-19: a review

Iron is a mineral that plays an important role, especially to prevent anaemia through the production of red blood cells. Iron also plays a role in physiological processes, such as the activation of enzymes and hormones, as well as increasing the immune system in warding off various viral infections. Therefore, iron bioavailability needs to be considered to take the greatest benefit of iron. This review discussed the factors that can affect the bioavailability of iron, various technologies to increase the bioavailability, and its potential in enhancing the immune system. Iron bioavailability can be increased by fortification, fermentation, the addition of vitamin C, and iron encapsulation. Under conditions of adequate iron intake, iron plays an important role in enhancing the immune system through controlling lymphocytes and T cell proliferation. However, excess iron consumption can be at risk of weakening the host's immune response to viruses. Therefore, the appropriate level of iron intake must be maintained accurately to be used optimally and has the potential to ward off viral infections, including the Sars-CoV-2 virus as the cause of COVID-19.Copyright © 2023, Rynnye Lyan Resources. All rights reserved.

Identification of selected earthworm species of Northeast India using DNA barcoding

Aim: This study aimed at the species identification of selected indigenous earthworms of Manipur and Assam, Northeast India along with an exotic species using morpho-anatomical study and DNA barcoding. Methodology: Indigenous species of earthworms were collected from Imphal and Jorhat, North-eastern part of India. The exotic species of earthworm were collected from Indian Council of Agricultural Research Complex, Manipur. The samples were collected by digging and hand sorting method. Identification of samples was done by both conventional and molecular methods. Molecular characterization was accomplished through PCR amplification of the mitochondrial cytochrome oxidase I (COI) genes. Automatic sequencing reactions were performed for the amplified PCR products on ABI3100 Genetic Analyser (Applied Biosystems). Result(s): Out of five specimens (EM1, EM2, EM4, EG5 and EM6) examined through morpho-anatomical studies, three were identified to species level while the other two were identified to their genus level only. Out of EM1 and EM2 specimens in the genus Perionyx as per the morpho-anatomical studies, DNA barcoding could deduce the EM2 specimen up to the species level as P. excavatus. The exotic EM6 specimen morphologically identified as Eisenia fetida showed 99% COI gene sequence similarity with both E. fetida and E. andrei but its sequence divergence with E. andrei was less than 1%, so, it belonged to E. andrei. Interpretation(s): This study shows the reliability of clubbing DNA barcoding experiments with classical taxonomy in supplementing and strengthening the traditional taxonomy for accurate identification of earthworms.Copyright © Triveni Enterprises, Lucknow (India)

Antiviral Effect of Ephedrine Alkaloids-Free Ephedra Herb Extract against SARS-CoV-2 In Vitro.

We report for the first time that ephedrine alkaloids-free Ephedra Herb extract (EFE) directly inhibits the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro and that the addition of EFE to the culture medium before viral infection reduces virus titers in the culture supernatant of SARS-CoV-2, including those of variant strains, by more than 99%, 24 h after infection. The addition of Ephedra Herb macromolecule condensed-tannin, which is the main active ingredient responsible for the anticancer, pain suppression, and anti-influenza effects of EFE, similarly suppressed virus production in the culture supernatant by 99% before infection and by more than 90% after infection. Since EFE does not have the side effects caused by ephedrine alkaloids, such as hypertension, palpitations, and insomnia, our results showed the potential of EFE as a safe therapeutic agent against coronavirus disease 2019.

A Review of Phytochemistry and Pharmacology on Moringa Oleifera

Natural extracts have been of very interest since ancient times due to their enormous medicinal use and research attention. Moringa oleifera is well known as miracle tree as it consists of high nutritive values. Originally from India is widely distributed in many tropical regions, in the pacific region, west Africa as well as central America. India is the major supplier of Moringa worldwide, accounting for around 80% of global demand. It is a multipurpose plant cultivated for medicinal applications. It contains rich sources of Vit- A, B1, B2, B3 and C, It also has calcium, potassium, iron, magnesium, zinc and phospherus. Moringa species contain various phytoconstituents such as alkaloids, saponins,tannins, steroids.phenolic acids( gallic, vanillic and p-coumaric acids) and flavanoids(catechin), tocopherol ,glucosinolates and terpenes. Investigations of ethanol extract of the leaves gives lutein, B-carotene,phytyl fatty acids, esters, poly phenols, B- sitosterols,triglycerols,fatty acids and saturated hydrocarbons. Leaves were obtained by super critical extraction with CO2 using ethanol as a cosolvent, temperature 35-80 0C.The phenolic acids( gallic, vanillic and p- coumaric acids) and flavanoids(catechin) were identified in all extracts. Extracts obtained at 35 degrees shows the highest values of total phenolic compounds. The activities of plant include Anti-oxidants, anti-cancer, anti-microbial, anti-viral,anti- hyperglycemic,anti-hyperlipidemic,anti-inflammatory,anti-hypertension, anti-spasmodic and others. Due to covid-19 pandemic, the global Moringa products market size is estimated to be worth USD 5167.2 million in 2022. Leaf powder is expected to exceed USD 6 billion by 2025 on account of increasing demand in the dietary supplement and food applications.

Antiviral activity of Cenostigma pluviosum var. peltophoroides extract and fractions against SARS-CoV-2.

Few extracts of plant species from the Brazilian flora have been validated from a pharmacological and clinical point of view, and it is important to determine whether their traditional use is proven by pharmacological effects. Cenostigma pluviosum var. peltophoroides is one of those plants, which belongs to the Fabaceae family that is widely used in traditional medicine and is very rich in tannins. Due to the lack of effective drugs to treat severe cases of Covid-19, the main protease of SARS-CoV-2 (Mpro) becomes an attractive target in the research for new antivirals since this enzyme is crucial for virus replication and does not have homologs in humans. This study aimed to prospect inhibitor candidates among the compounds from C. pluviosum extract, by virtual screening simulations using SARS-CoV-2 Mpro as target. Experimental validation was made by inhibitory proteolytic assays of recombinant Mpro and by antiviral activity with infected Vero cells. Docking simulations identify four compounds with potential inhibitory activity of Mpro present in the extract. The compound pentagalloylglucose showed the best result in proteolytic kinetics experiments, with suppression of recombinant Mpro activity by approximately 60%. However, in experiments with infected cells ethyl acetate fraction and sub-fractions, F2 and F4 of C. pluviosum extract performed better than pentagalloylglucose, reaching close to 100% of antiviral activity. The prominent activity of the extract fractions in infected cells may be a result of a synergistic effect from the different hydrolyzable tannins present, performing simultaneous action on Mpro and other targets from SARS-CoV-2 and host.Communicated by Ramaswamy H. Sarma.

Investigation of Potential Use of Soybean Protein Isolate-Chinese Bayberry Tannin Extract Cross-Linked Films in Packaging Applications.

The possibility of using commercial bayberry tannin (BT) from a Chinese source as a cross-linker and functional additive to develop soybean protein isolate (SPI)-based films was explored in this study by using the solvent casting method. In particular, the impacts of BT loading on the tensile strength, microstructure, thermal stability, water resistance and antioxidant capacity were fully investigated. The results reveal that SPI incorporated with BT yielded a phenolic-protein hybrid whose relevant films exhibited an improvement in tensile strength of around two times greater compared with native SPI as a result of the formed interactions and covalent cross-links, which could be proven using FTIR spectroscopy. The introduction of BT also led to the compact microstructure of SPI-BT films and enhanced the thermal stability, while the water vapor permeability was reduced compared with the control SPI film, especially at high loading content of tannin. Additionally, the use of BT significantly promoted the antioxidant capacity of the SPI-based films according to DPPH radical scavenging assay results. On this basis, Chinese bayberry tannin is considered a promising natural cross-linker and multifunctional additive that can be dedicated to developing protein-derived films with antioxidant activity for food packaging applications.

Phytochemical Contents, Biological Activities and Therapeutic Applications of Hedera Helix (Ivy Leaf) Extracts: A Review

Background: Herbs have long been used as natural therapeutics, and recent controlled clinical studies have confirmed some of the presumed benefits. Hedera helix(ivy leaves) is a valuable common form related to the family Araliaceae. Many herbal preparations include extracts from their leaves as the principle active ingredient. Objective: The objective of this article is to summarize the pharmacological activities and phyto-chemical screening of H. helix. Methods: To prepare this article, the data was collected from different sources, including books, th-esis, research and etc. Results: The all-published studies depend on isolation, identification, and characterization of different active constituents of H. helix leaves, followed by the determination of biological activities in vivo and in vivo. Chemical screening has shown that H. helix leaves are a rich source of phytochem-icals demonstrating therapeutic activities, such as sterols, tannins, terpenoids, glycosides, phenols, emetine alkaloids, flavonoids, saponins, volatile and fixed oils, vitamins, carbohydrates, reducing sugars, and minerals. Further, studies of disease models and clinical trials have demonstrated an-ti-inflammatory, analgesic, cough suppressant, expectorant, anticancer, antimicrobial, anticoagu-lant, and smooth muscle relaxant activities. Conclusion: This review summarizes the bioactive constituents of H. helix leaves and their under-lying pharmacological mechanisms, clinical efficacies, and safety profiles. We also suggest potential therapeutic uses for COVID-19.

Polyphenol and Tannin Nutraceuticals and Their Metabolites: How the Human Gut Microbiota Influences Their Properties.

Nutraceuticals have been receiving increasing attention in the last few years due to their potential role as adjuvants against non-communicable chronic diseases (cardiovascular disease, diabetes, cancer, etc.). However, a limited number of studies have been performed to evaluate the bioavailability of such compounds, and it is generally reported that a substantial elevation of their plasma concentration can only be achieved when they are consumed at pharmacological levels. Even so, positive effects have been reported associated with an average dietary consumption of several nutraceutical classes, meaning that the primary compound might not be solely responsible for all the biological effects. The in vivo activities of such biomolecules might be carried out by metabolites derived from gut microbiota fermentative transformation. This review discusses the structure and properties of phenolic nutraceuticals (i.e., polyphenols and tannins) and the putative role of the human gut microbiota in influencing the beneficial effects of such compounds.

Ayurvedic antiviral agents: Overview of medicinal plants perspective

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

Therapeutic potential of plant secondary metabolites in treatment of respiratory viral diseases: A review

Respiratory viral infections are a major public health concern because of their global occurrence, ease of spread and considerable morbidity and mortality. Medical treatments for viral respiratory diseases primarily involve providing relief from symptoms like pain and discomfort rather than treating the infection. Very few antiviral medications have been approved with restrictive usage, high cost, unwanted side effects and limited availability. Plants with their unique metabolite composition and high remedial values offer unique preventive and therapeutic efficacy in treatment of viral infections. The present review is focused on the types and mode of action of plant secondary metabolites that have been used successfully ί in the treatment of infections caused by respiratory viruses like Influenza, SARS, MERS, RSV etc. Plant metabolites such as phenolics, alkaloids, terpenoids and oligosaccharides inhibit attachment and entry of the virus. Others such as flavonoids, viz quercetin and baicalein, alkaloids viz sanguinarine, berberine and emetine, specific lipids and fatty acids prevent viral replication and protein synthesis. These metabolites have the potential to be used as lead molecules that can be optimized to develop potent drugs for effectively combating pandemics caused by respiratory viruses.

Evaluation of clinical efficacy of synthetic tannin and polidocanol-based agents and modern emollients in the hand eczema treatment. Use of new hand antiseptics during the pandemic in patients with hand eczema

Background. Patients with hand eczema account for 30–40% of dermatological patients. With the pandemic of new coronavirus infection COVID-19 and the need for frequent antiseptics use, there has been a steady increase in hand eczema incidence. The dominant symptoms in exacerbating eczema are skin inflammation and itching, which requires effective and safe skincare that is effective and safe. Objective. To evaluate the efficacy of the therapy with synthetic tannin and polidocanol-based agents and modern emollients, the time of resolution and degree of severity of clinical symptoms of eczema in patients, as well as the time and duration of remission, safety and compliance with sodium hypochlorite hand antiseptic spray. Materials and methods. Thirty-four patients with exacerbation of hand eczema were examined. The study was conducted in two stages. At the stage 1, before the remission, the patients received synthetic tannin and polidocanol-based agents and modern emollients;at the stage 2, monotherapy with modern emollients was used. Patients used sodium hypochlorite spray as a hand sanitizer throughout the study period. Results. The NESCI score became zero in 33 (96%) patients after the complex treatment of hand eczema. The Dermatology Life Quality Index by the end of stage 2 decreased 6-fold compared to the beginning of the study. No exacerbation of the dermatosis was observed in any of the patients included in the study during the use of sodium hypochlorite hand spray. Conclusion. The complex therapy with synthetic tannin, polidocanol-based agents, and modern emollients in hand eczema helps to achieve stable medical remission, decreases the itching intensity, and improves the patients’ quality of life. The use of new hand sanitizers during the pandemic in patients with hand eczema did not result in dermatosis exacerbations.

Evaluation of Peronema canescens Leaves Extract: Fourier Transform Infrared Analysis, Total Phenolic and Flavonoid Content, Antioxidant Capacity, and Radical Scavenger Activity

BACKGROUND: Peronema canescens (Sungkai) leaves have been popular in Indonesia which contain various bioactive compounds with empirical therapeutic efficacy in dealing with COVID-19 and various other diseases. Total phenolic and flavonoid content and antioxidant activity using the DPPH method from P. canescens leaf extract have not been studied much. AIM: This research has several objectives. The first is to compare the results of qualitative phytochemical analysis of the ethanol extract of the leaves of P. canescens (EEPL). The second is to measure the total phenol and flavonoid content. The third is to test the FTIR and antioxidant activity of the ethanol extract of P. canescens leaves in vitro using the DPPH method. METHODS: Fresh plant material and simplicia, ethanol extract extracted by maceration method using 96% ethanol as solvent from P. canescens. The Dragendorff’s and Mayer test carried out the qualitative phytochemical analysis, FeCl3 test, Salkowski method, Liebermann–Burchard method, foam test, and NaOH reagent. The total phenolic and flavonoid levels were tested using the Folin–Ciocalteu method. In vitro antioxidant activity was carried out using the DPPH (1,1-diphenyl-2-picrylhydrazyl) method. RESULTS: The results of qualitative phytochemical screening showed that alkaloids, flavonoids, saponins, tannins, and steroids were detected in the extract of P. canescens. The spectra from the FTIR test results showed various absorbance peak values indicating the bonding of specific functional groups, namely: 418.12, 599.94, 666.67, 1036.39, 1159.52, 1224.16, 1348.95, 1454.19, 1600.87, 1732.00, 2923.13, and 3353.01 cm-1. In the test results, total phenolic content was as much as 5.64% (mgEAG/g) and total flavonoid content of 142,247 mgEQ/g in a sample of 1 mg extract, which was equivalent to 1 mg quercetin. EEPL has antioxidant activity with the DPPH IC50 method of 116.7865 ppm. CONCLUSION: The data obtained at this time can contribute to the exploitation of P. canescens leaves in the future as one of the nutraceutical products, supplements, and herbal medicines by specific industries related to improving the health status of the world community. The higher the bioactive substance in preparation, the more significant the effect of the pharmacological efficacy response. P. canescens ethanol extract has good total phenolic content, total flavonoid content, and antioxidant action.

ORAL TANNINS REDUCE PROINFLAMMATORY CYTOKINES ASSOCIATED WITH DIARRHEA AND PNEUMONIA IN HOSPITALIZED COVID-19 PATIENTS

INTRODUCTION: There is evidence that the gut microbiota and its relationship with the immune system could be involved in the pathogenesis of COVID-19. SARS-CoV-2 can cause gastrointestinal symptoms during the early phases of the disease. Intestinal dysfunction induces changes in intestinal microbes, and an increase in inflammatory cytokines. Therefore, microbiota modulation could play a role in COVID-19 treatment. Tannins have been shown to work as prebiotics on the gastrointestinal microbiota. In particular, quebracho and chestnut tannins have shown to regulate the immune response and decrease in vitro-cytokines production, through microbiota fermentation-secondary metabolites, such as quercetin and SCFAs. OBJECTIVE: To evaluate the efficacy and the effect on cytokine levels of a tannin specific natural extract in COVID-19 patients. MATERIAL AND METHODS: This prospective, doubleblind, and randomized study was approved by the Hospital de Clínicas, José de San Martín (Buenos Aires, Argentina). Blood and stool samples were collected at baseline (Day 0) and after treatment (Day 14) during July-October 2020, with final follow-up in November 2020. We randomly assigned 124 RT-PCR confirmed COVID-19 cases (>18 years) to receive oral dry extracts of quebracho and chestnut tannins (240 mg) and B12 vitamin (0.72 μg) or placebo, twice daily for 14 days as adjunct treatment to their standard of care management. 27-pro and anti-inflammatory cytokines were measured on day 0 and 14 (Bio-Plex Pro™, Bio-Rad). Final enrollment of 140 patients with matched fecal microbiome characterization (16S, WGS and metabolites) is expected. RESULTS. Of 124 patients who were randomized (mean age 55+/-15, 63 [50.81%] male), 121 (97.58%) completed the trial. No adverse events were observed in the tannin group. Patients presenting with diarrhea (13%) had a trend to have elevated blood MIP-1α levels, which were significantly reduced by tannin treatment (Table 1). At baseline, higher levels of MIP-1α were also associated with diagnosis of pneumonia (Fig. 1), which was maintained after adjusting for confounders (age, sex, diabetes;p=0.04). Moreover, at baseline there was a positive correlation between MIP-1 α and IL-1ra, IL-2, MIP-1b and TNF-α, with all of these cytokines decreasing mostly with tannin treatment. CONCLUSION: To our knowledge, this clinical trial represents the first study to target the gut microbiome in hospitalized COVID-19 patients. Oral tannins as adjunct treatment with standard-of-care management of these patients significantly reduced proinflammatory cytokine levels that are generally associated with poor predictive outcomes, i.e. pneumonia and diarrhea. Further, our prospective studies will determine which microbiome-mediated mechanisms may attenuate the cytokine storm that is evident in COVID-19 disease pathogenesis. (Table presented) (Figure presented)