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175 SCIENCE BASED INGREDIENTS
THE MOST COMPREHENSIVE ALL NATURAL ANTIVIRAL FORMULA EVER CREATED
Featuring: 1-Dehydrogingerdione – Zingiber Officinale (Ginger)• 3,2᾿Dihydroxyflavone (3,2᾿Dhf) & 3,4᾿Dihydroxyflavone (3,4᾿Dhf) – Trifolium Repens L. • 6-Gingerol – Zingiber Officinale (Ginger)• Acidicheteroglucan – Tremella Fuciformis • Aconitum Carmichaelii Debx • Ailanthus Altissima Stem Bark • Allantoin – Glyoxylic Acid • Alphitonia Philippinensis Stems • Amygdalin – Semen Armeniacae Amarum • Anemarrhena Asphodeloides • Angelica Sinensis (Oliv.) Diels • Apigenin – Celery • Arctigerin, Arctin – Burdock (Arctium Lappa) • Artemisinin – Artemisia Annua • Aspalathin – Rooibos Tea • Atractylodin ,Β-Eudesmol, Hinesol, Hydroxy-Atractylo – Rhizoma Areactylodis Lanceae • Baicalein – Scutellaria Baicalensis Georgi • Benzaldehyde – Laurus Nobilis Leaves • Berberine – Coptis Chinensis • Beta-Sitosterol – Rice Bran Oil • Betulinic Acid – Betula Platyphylla Suk Bark • Bisdemethoxycurcumin – Turmeric Rhizome • Brachyamide B – Piper Boehmeriaefolium (Miq.) C. Dc • Bulbocapnine – Corydalis Decumbens(Thunb.) • Caffeic Acid – Cimicifuga Simplex (Dc.) Wormsk. Ex Turcz.Root • Calanolide A – Calophyllum Lanigerum • Campesterol – Rapeseed Oil • Carvacrol – Oregano • Chavicine – Black Pepper • Chelidimerine – Chelidonium Majus • Chlorogenic Acid – Green Coffee Bean • Chrysin – Pinus Mon-Ticola Dougl • Cinanserin – Cinnamic Acid • Cinnamomum Cassia Presl Dried Bark • Cirsilineol – Cirsium Lineare (Thunb.) Sch. • Cirsimaritin – Rabdosia Eriocalyx • Cis-Capsaicin (Civamide) – • Colchicine – Colchicum Autumnale L. • Cordifolioside A – Viola Verecunda • Crategolic Acid – Hawthorn • Curcumin – Turmeric Root • Cycloastragenol – Astragalus Membranaceus • Cyclocurcumin – Turmeric Root • Demethoxycurcumin – Turmeric Root • Dianthus Caryophyllus Seed – Carnation • Dioscin, Diosgenin – Wild Yam (Dioscorea Oppositae Thunb)• Douchi (Semen Sojae Praepatum) – Semen Sojae Praepatum • Egcg – Green Tea • Emodin – Rhubarb • Eriodictyol – Lemon • Eugenitin – Clove • Ferruginol – Podocarpus Ferruginea • Fisetin – Rhus Succedanea L • Flavonol Glucoside – Trichilia Connaroides Leaves • Forskolin – Coleus Forskohlii • Fructus Perillae – Perillafrutescens • Fumarophycine – Laptopyrum Reichb • Galangin – Alpinia Officinarum Hance Root • Gallic Acid – Rheumpalmatum L.Root • Genistein – Genista Tinctoria Linn Root • Glycyrrhizic Acid – Licorice Root • Gossypol – Cotton Seed • Guineensine – Piper Longum L. • Gypsum Fibrosum – Gypsum • Hawthorn Flavone – Crataegus Pinnatifida Bunge • Herba Dendrobii – Dendrobium Nobile Lindl • Herbacetin – Flaxseed • Hesperetin – Citrus Aurantium • –Hesperidin Nobiletin B-Phellandrene – Pericarpium Citri Reticulatae • Himachalol – Cupressus Funebris Endl. • Honokiol – Magnolia Officinalis • Houttuynia Cordata – Houttuynia Cordata Thunb • Hypericin Pseudohypericin Protohypericin – Forsythia Suspensa • Isochavicine – Pepper • Isoliquiritigenin – Glycyrrhiza Uralensisfisch Root • Isopiperine – Pepper • Isothymonin – Kaempferia Galanga L • Jatrorrhizine – Phellodendron Amurense Rupr. • Jujuboside A+B – Jujube • Kaempferol – Kaempferol Galanga L • Kaempferol 3-O-Robinobioside – Robinia Pseudoacacia L. • Leachianone – Morus Alba Root Bark • Lepidium Meyenii (Maca ) • Lily – Lilium Auratum • Luteoforol (A Flavan-4-Ol) – Peanut Shell • Luteolin – Peanut Shell • Lycoris Radiata – Lycoris Radiata (L’her.) Herb. • Macaranga Barteri Leaves • Maclura Cochinchinensis (Loureiro) Corner Root • Magnoflorine – Thalictrum Aquilegifolium Root • Marrubium Peregrinum L (Lamiaceae) • Meliacine – Melia Azedarach L • Mint – Mentha Haplocalyx Briq.• Morroniside,7-0-Methylmorroniside, Sweroside, Loganin, Cornus-Tannin 1,2,3 – Cornus Officinalis (Fructus Corni) • Morroniside,Cornus-Tannin 1,2,3 – Fructus Corni • Myricetin – Black Bayberry Fruit • Naringenin – Amacardi-Um Occidentale L.) • Ndoxyl-Β-Glucoside Uridine, Salicylic Acid,Daucosterol, Β-Sitostero – Radix Isatidis P.E (Satis Tinctoria L. Isatis Indigotica Fort.) • Nothofagin – Aspalathus Linearis • Oleanolic Acid – Olea Europaea L.Leaves • Olomoucine Ii – • Ophiocarpine – Corydalis Ophiocarpa Hook. F. Et Thoms • Ophiopogonin A B C D – Ophiopogon Root • Orientin – Globeflower • Oxypeucedanin Stiamasterol Β-Sitosterol Β-Daucosterin – Angelica Dahurica • Paeoniflorin – Radix Paeoniae Rubra • Patrinia Villosa Juss. – Patrinia Villosa (Thunb. ) Juss. • Peach Kernel – Emen Persicae • Pectolinarin – Linaria Vulgaris Hill Subsp. • Pelargonium Sidoides – Pelargonium Peltatum (L.) Ait. • Pentadienoylpiperidine – Pepper • Phragmitescommunis Trin – Phragmites Australis (Cav.) Trin. Ex Steud • Phyllanthus Orbicularis – Phyllanthus Orbicularis Kunth • Pinusolidic Acid – Vanillin & Malonic Acid • Piperettine – Pepper • Pipericide – Pepper • Piperine – Pepper • Piperolein B – Pepper • Poria Cocos Polysaccharide – Poria Cocos(Schw.)Wolf. • Protocatechuic Acid – Stenoloma Chusanum(L.) Ching Leaves • Protopine – Corydalis Yanhusuo W.T.Wang • Quercetin – Sophora Japonica • Quercetin-3-B-Galactoside – St. John’s Wort • Quercetin-3,7-O-Α-L-Dirhamnoside (Quercitrin) – Sabina Pingii Var. Wilsonii • Quinic Acid – Cinchona Bark • Radix Codonopsis Root • Radix Glehniae – Coasiai Giehnia Root • Radix Platycodonis Platycodigenin, Polygalacic Acid – Platycodon Grandiflorum Root • Radix Scrophulariae Root • Reserpine – Rauvolfia Verticillata (Lour.) Baill. • Resveratrol – Polygonum Cuspidatum • Retrofractamide A – Black Pepper • Rhamnetin – Syzygium Aromaticum • Rhizoma Atractylodis Macrocephalae Root • Rhizoma Pinelliae – Pinellia Ternata (Thunb.) Breit • Rhoifolin – Turpinia Arguya Seem Leaves • Rosmarinic Acid – Rosemary • Rupestonic Acid – Artemisia Rupestris L. • Rutin – Ruta Graveolens L. • Saikosapoins A B C D – Bupleurum (Radix Stellariae) • Salicin – Salix Babylonical Bark • Salidroside, Rosavine, Rosin,Rosarin,Rhodiolin – Rhodiola Rosea • Samarangenin B – Limonium Bicolor (Bag.) Kuntze • Saposhnikovia Divaricata (Trucz.) Schischk Root • Savinin • Schisandrin, Deoxyschisandrin, Neoschisandrin – Schisandra Chinensis • Schizonepeta Tenusfolia Briq Dried Flower • Selaginella Moellendorfii Hieron • Semen Lepidii Semen Descurainiae – Eruca Sativa Mill • Silibinin – Milk Thistle • Silymarin – Milk Thistle • Solanum Rantonnetii Aerial Parts Extact – Lycianthes Rantonnetii Bitter • Somniferine – Ashwagandha/Ajagandha/Kanaje • Stigmasterol – Soybean • Synephrine – Citrus Aurantium Powde • Taxillus Sutchuenensis – Taxillus Sutchuenensis (Lecomte ) Danser • Tinocordifolin – Tinospora Cordifolia • Tinocordifolioside – Tinospora Cordifolia • Tinosporide – Tinospora Cordifolia • Trichostachine – Piper Hancei Maxim • Triterpenoid Saponins – Trichosanthes Kirilowii (Mongolian Snakegourd Fruit) • Umbelliferone – Ruta Graveolens L. • Ursolic Acid – Loquat Leaf • Valinomycin – Bacterium Streptomyces • Verbascum Thapsus L – Mullein • Vicenin – Desmodium Styracifolium • Vincamine – Catharanthus Roseus (L.)G. Don • Vitex Polygama – Vitex Negundo L. Var. Cannabifolia (Sieb. Et Zucc.) Hand.-Mazz • Withaferin A – Ashwagandha • Withanolide – Ashwagandha • Withanolide B – Ashwagandha • Withanone – Ashwaganda • Wogonin – Scutellaria Baicalensis (Radix Scutellariae) • Wrinkled Gianthyssop Herb – Agastache Rugosa (Fisch. Et Mey.) O. Ktze. • Yohimbine – Yohimbe Bark
200:1 CONCENTRATION
VERY POTENT
300 1/8 tsp servings per 100g bag.
Take 1/8 -1/4 serving 2-4 times a day.
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ANTIVIRAL EFFECTS OF FLAVONOIDS AND POLYPHENOLS (THOUSANDS OF STUDIES – CLICK TO READ)
May Polyphenols Have a Role Against Coronavirus Infection? An Overview of the Evidence
Overall, this evidence suggests that polyphenols may exert a marked and well-demonstrated activity against coronaviruses, at least in vitro, in addition to the previously demonstrated antiviral activity in vivo. Studies available in the literature agree in establishing that the reduction of virus titer and the inhibition of nucleocapsid protein expression are their main general mechanisms of action at the base of this promising effect of polyphenols. These elucidated mechanisms are of great interest, since nowadays no effective treatments have been licensed, and the development of novel synthetic drugs against specific coronavirus molecular targets are still far from being achieved.
Antiviral effect of flavonoids on human viruses
The effect of several naturally occurring dietary flavonoids including quercetin, naringin, hesperetin, and catechin on the infectivity and replication of herpes simplex virus type 1 (HSV-1), polio-virus type 1, parainfluenza virus type 3 (Pf-3), and respiratory syncytial virus (RSV) was studied in vitro in cell culture monolayers employing the technique of viral plaque reduction. Quercetin caused a concentration-dependent reduction in the infectivity of each virus. In addition, it reduced intracellular replication of each virus when monolayers were infected and subsequently cultured in medium containing quercetin. Preincubation of tissue culture cell monolayers with quercetin did not affect the ability of the viruses to infect or replicate in the tissue culture monolayers. Hesperetin had no effect on infectivity but it reduced intracellular replication of each of the viruses. Catechin inhibited the infectivity but not the replication of RSV and HSV-1 and had negligible effects on the other viruses. Naringin had no effect on either the infectivity or the replication of any of the viruses studied. Thus, naturally occurring flavonoids possess a variable spectrum of antiviral activity against certain RNA (RSV, Pf-3, polio) and DNA (HSV-1) viruses acting to inhibit infectivity and/or replication.
Discovery of anti-2019-nCoV agents toward respiratory diseases via docking screening
The 2019 novel coronavirus (2019-nCoV) causes novel coronavirus pneumonia (NCP). Given that approved drug repurposing becomes a common strategy to quickly find antiviral treatments, a collection of FDA-approved drugs can be powerful resources for new anti-NCP indication discoveries. In addition to synthetic compounds, Chinese Patent Drugs (CPD), also play a key role in the treatment of virus related infections diseases in China. Here we compiled major components from 38 CPDs that are commonly used in the respiratory diseases and docked them against two drug targets, ACE2 receptor and viral main protease. According to our docking screening, 10 antiviral components, including hesperidin, saikosaponin A, rutin, corosolic acid, verbascoside, baicalin, glycyrrhizin, mulberroside A, cynaroside, and bilirubin, can directly bind to both host cell target ACE2 receptor and viral target main protease. In combination of the docking results, the natural abundance of the substances, and botanical knowledge, we proposed that artemisinin, rutin, glycyrrhizin, cholic acid, hyodeoxycholic acid, puerarin, oleanic acid, andrographolide, matrine, codeine, morphine, chlorogenic acid, and baicalin (or Yinhuang Injection containing chlorogenic acid and baicalin) might be of value for clinical trials during a 2019-nCov outbreak.
A recent outbreak of the novel coronavirus, COVID‐19, in the city of Wuhan, Hubei province, China and its ensuing worldwide spread have resulted in lakhs of infections and thousands of deaths. As of now, there are no registered therapies for treating the contagious COVID‐19 infections, henceforth drug repositioning may provide a fast way out. In the present study, a total of thirty-five compounds including commonly used anti-viral drugs were screened against chymotrypsin-like protease (3CLpro) using SwissDock. Interaction between amino acid of targeted protein and ligands was visualized by UCSF Chimera. Docking studies revealed that the phytochemicals such as cordifolin, anisofolin A, apigenin 7-glucoside, luteolin, laballenic acid, quercetin, luteolin-4-glucoside exhibited significant binding energy with the enzyme viz. – 8.77, -8.72, -8.36, -8.35, -8.13, -8.04 and -7.87 Kcal/Mol respectively. Therefore, new lead compounds can be used for drug development against SARS‐CoV‐2 infections.
COVID-19, a rapidly spreading new strain of coronavirus, has affected more than 150 countries and received worldwide attention. The lack of efficacious drugs or vaccines against SARS-CoV-2 has further worsened the situation. Thus, there is an urgent need to boost up research for the development of effective therapeutics and affordable diagnostic against COVID-19. The crystallized form of SARS-CoV-2 main protease (Mpro) was demonstrated by a Chinese researcher Liu et al. (2020) which is a novel therapeutic drug target. This study was conducted to evaluate the efficacy of medicinal plant-based bioactive compounds against COVID-19 Mpro by molecular docking study. Molecular docking investigations were performed by using Molegro Virtual Docker 7 to analyze the inhibition probability of these compounds against COVID-19. COVID-19 Mpro was docked with 80 flavonoid compounds and the binding energies were obtained from the docking of (PDB ID: 6LU7: Resolution 2.16 Å) with the native ligand. According to obtained results, hesperidin, rutin, diosmin, apiin, diacetylcurcumin, (E)-1-(2-Hydroxy-4-methoxyphenyl)-3-[3-[(E)-3-(2-hydroxy-4- methoxyphenyl)-3-oxoprop-1-enyl]phenyl]prop-2-en-1-one, and beta,beta’-(4-Methoxy-1,3- phenylene)bis(2′-hydroxy-4′,6′-dimethoxyacrylophenone have been found as more effective on COVID-19 than nelfinavir. So, this study will pave a way for doing advanced experimental research to evaluate the real medicinal potential of these compounds to cure COVID-19.
Potential of Flavonoid-Inspired Phytomedicines against COVID-19
Flavonoids are widely used as phytomedicines. Here, we report on flavonoid phytomedicines with potential for development into prophylactics or therapeutics against coronavirus disease 2019 (COVID-19). These flavonoid-based phytomedicines include: caflanone, Equivir, hesperetin, myricetin, and Linebacker. Our in silico studies show that these flavonoid-based molecules can bind with high affinity to the spike protein, helicase, and protease sites on the ACE2 receptor used by the severe acute respiratory syndrome coronavirus 2 to infect cells and cause COVID-19. Meanwhile, in vitro studies show potential of caflanone to inhibit virus entry factors including, ABL-2, cathepsin L, cytokines (IL-1β, IL-6, IL-8, Mip-1α, TNF-α), and PI4Kiiiβ as well as AXL-2, which facilitates mother-to-fetus transmission of coronavirus.
Since most of the drug candidates presently available for COVID-19 substantially act on viral main protease, by using molecular docking analysis, we have predicted the protease inhibitor activity of several natural products that can emerge as potential drug candidates inhibiting viral protease. A promising binding of natural products with the COVID-19 main protease was revealed by docking analysis. Among the several natural products screened by docking analysis, glycyrrhizin, tryptanthrine, rhein, and berberine were found to exhibit a higher degree of interaction with the viral protease accompanied by lowest binding energy with favorable drug-like properties. Thus these natural products may emerge as potential COVID-19 main protease inhibitor. However, additional exploration is inevitable for the investigation of the inherent use of the herbs containing these natural products and their in-vivo activity.
Targeting SARS-CoV-2 Spike Protein of COVID-19 with Naturally Occurring Phytochemicals
Spike glycoprotein found on the surface of SARS-CoV-2 (SARS-CoV-2S) is a class I fusion protein which helps the virus in its initial attachment with human Angiotensin converting enzyme 2 (ACE2) receptor and its consecutive fusion with the host cells. The attachment is mediated by the S1 subunit of the protein via its receptor binding domain. Upon binding with the receptor the protein changes its conformation from a pre-fusion to a post-fusion form. The membrane fusion and internalization of the virus is brought about by the S2 domain of the spike protein. From ancient times people have relied on naturally occurring substances like phytochemicals to fight against diseases and infection. Among these phytochemicals, flavonoids and non-flavonoids have been found to be the active source of different anti-microbial agents. Recently, studies have shown that these phytochemicals have essential anti-viral activities. We performed a molecular docking study using 10 potential naturally occurring flavonoids/non-flavonoids against the SARS-CoV-2 spike protein and compared their affinity with the FDA approved drug hydroxychloroquine (HCQ). Interestingly, the docking analysis suggested that C-terminal of S1 domain and S2 domain of the spike protein are important for binding with these compounds. Kamferol, curcumin, pterostilbene, and HCQ interact with the C-terminal of S1 domain with binding energies of -7.4, -7.1, -6.7 and -5.6 Kcal/mol, respectively. Fisetin, quercetin, isorhamnetin, genistein, luteolin, resveratrol and apigenin on the other hand, interact with the S2 domain of spike protein with the binding energies of -8.5, -8.5, -8.3, -8.2, -8.2, -7.9, -7.7 Kcal/mol, respectively. Our study suggested that, these flavonoid and non-flavonoid moieties have significantly high binding affinity for the two main important domains of the spike protein which is responsible for the attachment and internalization of the virus in the host cell and their binding affinities are much higher compared to that of HCQ. In addition, ADME (absorption, distribution, metabolism and excretion) analysis also suggested that these compounds consist of drug likeness property which may help for further explore as anti-SARS-CoV-2 agents. Further, in vitro and in vivo study of these compounds will provide a clear path for the development of novel compounds that would most likely prevent the receptor binding or internalization of the SARS-CoV-2 spike protein and therefore could be used as drugs for COVID-19 therapy.
Roles of flavonoids against coronavirus infection
In terms of public health, the 21st century has been characterized by coronavirus pandemics: in 2002-03 the virus SARS-CoV caused SARS; in 2012 MERS-CoV emerged and in 2019 a new human betacoronavirus strain, called SARS-CoV-2, caused the unprecedented COVID-19 outbreak. During the course of the current epidemic, medical challenges to save lives and scientific research aimed to reveal the genetic evolution and the biochemistry of the vital cycle of the new pathogen could lead to new preventive and therapeutic strategies against SARS-CoV-2. Up to now, there is no cure for COVID-19 and waiting for an efficacious vaccine, the development of “savage” protocols, based on “old” anti-inflammatory and anti-viral drugs represents a valid and alternative therapeutic approach. As an alternative or additional therapeutic/preventive option, different in silico and in vitro studies demonstrated that small natural molecules, belonging to polyphenols family, can interfere with various stages of coronavirus entry and replication cycle. Here, we reviewed the capacity of well-known (e.g. quercetin, baicalin, luteolin, hesperetin, gallocatechin gallate, epigallocatechin gallate) and uncommon (e.g. scutellarein, amentoflavone, papyriflavonol A) flavonoids, secondary metabolites widely present in plant tissues with antioxidant and anti-microbial functions, to inhibit key proteins involved in coronavirus infective cycle, such as PLpro, 3CLpro, NTPase/helicase. Due to their pleiotropic activities and lack of systemic toxicity, flavonoids and their derivative may represent target compounds to be tested in future clinical trials to enrich the drug arsenal against coronavirus infections.
In conclusion, the interest of scientists for the antiviral capacity of flavonoids against human coronavirus infections can benefit of the enormous amount of resources that governments, health agencies, and private companies are pouring in the field, searching for a cure against SARS-CoV-2. This situation barely resembles what happened in the eighties-nineties following the AIDS pandemic, when the basic knowledge in the immunological mechanisms controlling the response to HIV infection underwent amazing and unpredictable progresses. Waiting for a valuable vaccine against COVID-19, the pharmacological approach remains a priority and flavonoids may contribute to it. In this scenario, the “pleiotropic” properties of flavonoids that we mentioned at the beginning of this review, risks to become the passepartout to counteract coronaviruses since they can be effective on both sides, viral and host cells, to inhibit infection. In fact, recent works hypothesized that flavonoids can inhibit both TMPRSS2 and Furin, which cleave the SARS-CoV-2 Spike protein facilitating SARS-CoV-2 infectivity. Molecular docking-based screening and in vitro assays using recombinant proteins indicated that (−)-epicatechin 3-O-(3′-O-methyl) gallate for TMPRSS2 [84] and baicalein and oroxylin A glycoside for Furin [85] can bind and inhibit their respective proteases blocking virus propagation.
INGREDIENTS:
3,2᾿dihydroxyflavone
(3,2᾿DHF) & 3,4᾿dihydroxyflavone (3,4᾿DHF)
(Trifolium repens L.)
Influenza virus infection causes thousands of deaths and millions of hospitalizations worldwide every year and the emergence of resistance to anti-influenza drugs has prompted scientists to seek new natural antiviral materials. In this study, we screened 13 different flavonoids from various flavonoid groups to identify the most potent antiviral flavonoid against human influenza A/PR/8/34 (H1N1). The 3-hydroxyl group flavonoids, including 3,2᾿dihydroxyflavone (3,2᾿DHF) and 3,4᾿dihydroxyflavone (3,4᾿DHF), showed potent anti-influenza activity. They inhibited viral neuraminidase activity and viral adsorption onto cells. To confirm the anti-influenza activity of these flavonoids, we used an in vivo mouse model. In mice infected with human influenza, oral administration of 3,4᾿DHF significantly decreased virus titers and pathological changes in the lung and reduced body weight loss and death. Our data suggest that 3-hydroxyl group flavonoids, particularly 3,4᾿DHF, have potent antiviral activity against human influenza A/PR/8/34 (H1N1) in vitro and in vivo. Further clinical studies are needed to investigate the therapeutic and prophylactic potential of the 3-hydroxyl group flavonoids in treating influenza pandemics.
6-gingerol
(ginger extract)
Acidicheteroglucan
(Tremella fuciformis extract)
Aconitum carmichaelii Debx extract
(Aconitum carmichaelii Debx)
Four diterpenoid alkaloids, namely, (a) hypaconitine, (b) songorine, (c) mesaconitine and (d) aconitine, were isolated from the ethanol root extract of Aconitum carmichaelii Debx. The antiviral activities of these alkaloids against tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV) were evaluated. Antiviral activity test in vivo showed that compounds a and c, which were C19-diterpenoid alkaloids, showed inactivation efficacy values of 82.4 and 85.6% against TMV at 500 μg/mL, respectively. By contrast, compound c presented inactivation activity of 52.1% against CMV at 500 μg/mL, which was almost equal to that of the commercial Ningnanmycin (87.1% inactivation activity against TMV and 53.8% inactivation activity against CMV). C19-Diterpenoid alkaloids displayed moderate to high antiviral activity against TMV and CMV at 500 μg/mL, dosage plays an important role in antiviral activities. This paper is the first report on the evolution of aconite diterpenoid alkaloids for antiviral activity against CMV.
Ailanthus altissima stem bark extract
(Ailanthus altissima (Mill.) Swingle)
In order to search for the anti-HIV agents from natural products, eighty MeOH extracts of medicinal plants were applied to a syncytia formation inhibition assay which is based on the interaction between the HIV-1 envelope glycoprotein gp120/gp41 and the cellular membrane protein CD4 of T lymphocytes. Among them, Ailanthus altissima showed a potent virus-cell fusion inhibitory activity.
allantoin
(Glyoxylic acid)
Alphitonia philippinensis stems
(Alphitonia philippinensis Braid)
Three new flavonol glycosides, namely, isorhamnetin 3-O-(6″-O-(Z)-p-coumaroyl)-β-d-glucopyranoside, quercetin 3-O-α-l-rhamnopyranosyl(1-2)-α-l-arabinopyranosyl(1-2)-α-l-rhamnopyranoside, and quercetin 3-O-α-l-arabinopyranosyl(1-2)-α-l-rhamnopyranoside, were isolated from the stems of Alphitonia philippinensis collected from Hainan Island, China. Some of the isolated triterpenoids and flavonoid glycosides showed cytotoxicity against human PC-3 cells and hepatoma HA22T cells, and the inhibition of replication on HSV-1 (131). Viral diseases, especially of skin, can be treated with a virucide encapsulated in multilamellar phospholipid liposomes. Rosmarinic acid (70), incorporated in phospholipid mixture demonstrated effectiveness in humans afflicted with HSV (132). Flavonol glycosides (from quercetin and isorhamnetin) derived from the stems of Alphitonia philippinensis have been reported to inhibit the replication of HSV-1.
Amygdalin
(Semen Armeniacae Amarum Extract)
Contribution of traditional Chinese medicine to the treatment of COVID-19
Amygdalin could Inhibit IFN-γ, NF-κB and NLRP3 signaling pathways so as to reduce the inflammatory response (Paoletti et al., 2013; Zhang et al., 2017). These reports provided the scientific ground of integrating TCM therapy from the aspects of their compositions’ potential targeting proteins and signaling pathways in the treatment of COVID-19.
Anemarrhena asphodeloides extract
(Anemarrhena asphodeloides Bunge)
Two known steroidal saponins, timosaponin A-III (1) and anemarsaponin B (2) were isolated from the BuOH fraction of the rhizomes of Anemarrhena asphodeloides Bunge (Liliaceae) together with the xanthone derivatives, mangiferin (3) and neomangiferin (4). Structures of the isolates were identified using 1D and 2D NMR techniques and by comparison with the published values. Timosaponin A-III (1) exhibited potent inhibitory effects on the respiratory syncytial virus (RSV), with an IC50 value of 1.00 µM.
Angelica sinensis
(Angelica sinensis (Oliv.) Diels)
Increased oxidative stress and disturbed glutathione redox system play an important role in the pathogenesis of human immunodeficiency virus (HIV) infection. Depletion in intracellular levels of reduced glutathione (GSH) contributes to an increment in tumor necrosis factor α (TNF-α)-stimulated-HIV-1-transcription, activation of HIV-1-replication, sensitivity to TNF-α-induced cell death, and impairment of CD4+ cell function and survival. Therefore, several studies have investigated the effect of GSH-enhancer agents such as N-acetyl cystein in the treatment of patients with HIV infection. With regard to the beneficial effects of Angelica sinensis, a Chinese medicinal herb, on GSH redox system and the pathogenic role of GSH depletion in HIV infection and the immunomodulator effects of active ingredients of this herb, we postulated that Angelica sinensis may be of value in the treatment of HIV-infected patients.
Targeting SARS-CoV-2 Spike Protein of COVID-19 with Naturally Occurring Phytochemicals
Apigenin has shown potent antiviral activity against hepatitis B virus, adenoviruses, african swine fever virus and some RNA viruses in vitro.
arctigeNin, arctin
(Burdock extract (Arctium Lappa))
Arctiin and its aglucone, arctigenin from the fruits of Arctium lappa L. showed potent in vitro antiviral activities against influenza A virus (A/NWS/33, H1N1) (IFV). Based on the data from time-of-addition experiments and on release tests of progeny viruses, arctigenin was assumed to interfere with early event(s) of viral replication after viral penetration into cells, and to suppress the release of progeny viruses from the host cells. Arctiin was orally effective against either IFV-inoculated normal or 5-fluorouracil (5-FU)-treated mice, being less effective as compared with oseltamivir. Noticeably, arctiin produced a larger amount of virus-specific antibody than those of control and oseltamivir in sera collected from 5-FU-treated mice. Furthermore, oral treatment of 5-FU-treated mice with arctiin did not induce any resistant viruses, although the same treatment with oseltamivir induced resistant viruses at a 50% frequency. When the combination of arctiin and oseltamivir was administered to normal mice infected with IFV, the virus yields in both bronchoalveolar lavage fluids and lungs were significantly reduced relative to those in the mice treated with arctiin or oseltamivir alone. Thus, monotherapy of arctiin or combined therapy of arctiin with oseltamivir would be another treatment option for influenza.
artemisinin
(Artemisia annua extract)
Discuss about the application of Artemisia annua prescriptions in the treatment of COVID-19
The applications of traditional Chinese medicine (TCM) have been playing an important role in treating the epidemics of Coronavirus Disease 2019 (COVID-19), which is now prevalent all over the world. Exploring the mechanisms of TCM compound prescriptions might be difficult though, pharmacological studies on elucidating the effective components of TCM could serve as the experimental basis in the application of TCM compound prescription in treating COVID-19. As the critical active ingredients of Qinghao (Artemisia annua), artemisinin was initially used as antimalaria drug. Artemisia annua prescriptions take significant effect against pneumonia. Sharing similarities in pharmacology with artemisinin, chloroquine has been confirmed effective in inhibiting Severe Acute Respiratory Syndrome coronavirus 2 (SARS-Cov-2) both in vitro and practically. In this context, we discussed the application of Artemisia annua prescriptions against COVID-19 along with the antiviral effect of chloroquine.
Conclusion
With similar pharmacological effects between chloroquine and artemisinin in treating infectious diseases, this paper discusses the modern scientific basis for the application of Artemisia annua prescriptions in COVID-19. Except for antimalarial, most of the other pharmacological studies on artemisinin and its derivatives are still on the bench or at animal level, with only a few in clinical trials. Artemisinin treatment on COVID-19 has not been reported yet. As a treasure of TCM, compound prescription has played an important role in plagues in history. The main cause of COVID-19 in Wuhan is damp-heat according to TCM theory. The prescription for clearing heat and eliminating dampness based on Artemisia annua is widely used in this epidemic. Based on the antiviral and anti-inflammatory effects of artemisinin and its derivatives, Artemisia annua prescriptions have great value to dig into and are promising to be used in more infectious diseases. But more in vitro experiments need to be carried out to provide more evidence, such as the influence of Artemisia or Artemisia annua prescriptions on inflammatory factors express
aspalathin
(ROOIBOS tea)
Aspalathus Linearis (Burm.f.) R. Dahlrgen (Rooibos)
atractylodin ,β-eudesmol,hinesol,hydroxy-atractylo
(Rhizoma Areactylodis Lanceae extract)
Baicalein
(Scutellaria baicalensis Georgi)