WO2023121486A1 - Compositions and compounds for treating covid-19 - Google Patents

Compositions and compounds for treating covid-19 Download PDF

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Publication number
WO2023121486A1
WO2023121486A1 PCT/PH2021/050044 PH2021050044W WO2023121486A1 WO 2023121486 A1 WO2023121486 A1 WO 2023121486A1 PH 2021050044 W PH2021050044 W PH 2021050044W WO 2023121486 A1 WO2023121486 A1 WO 2023121486A1
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methyl
oxy
composition
covid
deoxy
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PCT/PH2021/050044
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French (fr)
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Mitchell Medina
Paul CHEPKWONY
Maria JAYLO-MEDINA
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International Patent Holdings Llc
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Priority to PCT/PH2021/050044 priority Critical patent/WO2023121486A1/en
Publication of WO2023121486A1 publication Critical patent/WO2023121486A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/24—Apocynaceae (Dogbane family), e.g. plumeria or periwinkle
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/47—Euphorbiaceae (Spurge family), e.g. Ricinus (castorbean)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/68—Plantaginaceae (Plantain Family)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/71—Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
    • A61K36/716—Clematis (leather flower)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/72—Rhamnaceae (Buckthorn family), e.g. buckthorn, chewstick or umbrella-tree
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
    • A61K36/736—Prunus, e.g. plum, cherry, peach, apricot or almond
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/76—Salicaceae (Willow family), e.g. poplar
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/77—Sapindaceae (Soapberry family), e.g. lychee or soapberry
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/896—Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
    • A61K36/8965—Asparagus, e.g. garden asparagus or asparagus fern
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses

Definitions

  • SARS- CoV-2 evolved during advanced HIV disease immunosuppression has Beta-like escape of vaccine and Delta infection elicited immunity.
  • medRxiv preprint https://doi.org/10.1101/2021.09.14.21263564 Chen R.H., Yang L.J., Hamdoun S., Chung S.K., Lam C.W., Zhang K.X., Guo X., Xia C., Law B.Y.K. & Wong V.K.W. (2021, March 4) 1,2,3,4,6- pentagalloyl glucose, a RBD-ACE2 binding inhibitor to prevent SARSCoV-2 infection. Frontiers in Pharmacology 12:634176.
  • the instant invention relates to treatment of the novel coronavirus disease of 2019 (COVID-19). More specifically, this application discloses compositions of, and compounds found, in combinations of up to 14 Kenyan plants, including Dovyalis abyssinica and clutia robusta, which are effective in treating COVID-19 in humans. BACKGROUND OF THE INVENTION
  • prior patents to the present inventors that are identically assigned to this application are referenced and sometimes cited at length, specifically: U.S. Patent Nos.
  • Molnupiravir This is pronounced of Merck’s Molnupiravir, which was at first claimed as effecting a 50% reduction in hospitalizations, a number which was later lowered to 30% (Kozlov, M., 2021, December 13). Molnupiravir has also raised concerns in some quarters over its mutagenic mechanism of action (Cohen, J. & Piller C., 2020, May 13) and, at a minimum, is not recommended for pregnant women for those reasons.
  • Various monoclonal antibodies have been proposed, studied, or granted emergency use authorization (in at least one case later suspended). They include casirivimab/imdevimab, bamlanivimab/etesevimab, and bamlanivimab.
  • the Omicron variant has significant escape from both vaccine- and infection-elicited immunity (Zhang et. al, 2021, December 10).
  • Initial assessments that the Omicron variant is less virulent than earlier strains have been disputed by British scientists (Ferguson, et al., 2021, December 16). Future variants may be even more intractable. 89% of epidemiologists polled in a survey expressed the view that COVID-19 is very likely or likely to become endemic (Philips, N. (2021, February 18), even with vaccines in existence. In this scenario, and despite the efforts that have been made heretofore, the urgent need for COVID-19 therapeutics which is felt worldwide remains undiminished.
  • hydroxychloroquine, ribavirin, lopinavir, favipiravir, ritonavir, ivermectin, umifenovir and camostat mesylate are among the existing medications that have been studied in connection with their potential usefulness in treating COVID-19 (Verma et al., September 2020, p. 3). Medicines other than Applicants’ that were developed for HIV/AIDS have not been shown to work. “Although some ARV drugs are being studied for the prevention and treatment of COVID-19, no agents have been shown to be effective.” (COVID-19 Guidelines Panel, op. cit., p. 308).
  • TCM Chinese herbal medicines
  • Lianhua Qingwen Lianhua Qingwen.
  • Lianhau Qingwen has been licensed as a prescription medicine by the Philippines F.D.A., but not for the treatment of COVID-19 (Philippines Food and Drug Administration 2021, April 30, and April 5). It is also approved in some other jurisdictions. It does not contain any of Applicants’ plant species.
  • TCM Chinese herbal medicines
  • any given plant may contain a plurality of pharmacologically active chemical compounds, and that these compounds may function synergistically to create a therapeutic effect (Prasad et. al. 2020, June 19).
  • the potential synergies can be exponentially increased when combination therapy with a plurality of plants is deployed (Spjut, R., 2005, p. 2223), as in the instant application.
  • Spjut p. 2221
  • compositions and compounds have previously been disclosed and experimentally validated in the treatment of HIV/AIDS in humans, producing sero-reversion in some cases. Unpredictably, those same compositions and compounds are also useful in the treatment of COVID-19. Many proposed repurposed therapies for COVID-19 have failed. The example of hydroxychloroquine is well known (W.H.O. 2021, May 21). Applicants’ unexpected success where others have failed is evidence of invention, and should not be taken as an inherent sign of lack of credibility. SUMMARY OF THE INVENTION The present invention is based upon the discovery of the unique antiviral properties of a herbal remedy composition prepared from a variety of plants native to Kenya.
  • the herbal composition of the present invention can include plant material from between two and 14 different plants including Dovyalis abyssinica (representative seed of said line having been deposited under ATCC Accession No. PTA-6969) and Clutia robusta (representative seed of said line having been deposited under ATCC Accession No. PTA-6970).
  • the herbal pharmaceutical composition may also include plant material from one or more of the following: Prunus africana, Croton macrostachyus, Acacia nilotica (representative seed of said line having been deposited under ATCC Accession No.
  • the invention provides a herbal composition for treating infectious diseases, such as for example, COVID-19.
  • the composition containing plant material includes the roots of Dovyalis abyssinica and the roots of Clutia robusta.
  • the herbal pharmaceutical composition may also include plant material, as indicated, from one or more of the following: stem bark of Prunus africana, stem bark of Croton macrostachyus, stem bark of Acacia nilotica, roots of Rhamnus prinoides, roots of Adenia gummifera, roots of Asparagus africanus, stem bark of Anthocleista grandiflora, whole plant of Plantago palmata, roots of Clematis hirsuta, stem bark of Ekebergia capensis, stem bark of Bersama abyssinica, and roots of Periploca linearifolia.
  • the invention provides illustrative methods for preparing a liquid extract of the solid herbal composition of the invention.
  • the extraction of plant material can be done with hot water.
  • the aqueous extract can be used for treating COVID-19.
  • hot aqueous extraction is done under basic conditions, followed by hot aqueous extraction under acidic conditions.
  • extracts of the herbal compositions can be processed to produce a concentrate in semi- solid or solid form, ground when dry to create a powder, and further processed to make a pharmaceutical composition. If required, herbal extracts and/or concentrates can be processed, washed and/or cleaned to remove toxic residues or compounds.
  • the subject invention provides illustrative processes for preparing the composition disclosed herein comprising isolating compounds from one or more plant sources. It is known in the art that “.... phytotherapeutics with multiple therapeutic uses likely contain several different active constituents or contain compounds with work synergistically to produce the desired therapeutic effects” (Ruiz et. al, 2016, July 26). Compounds isolated by applicants which are thought to be candidates in the production of the synergistic therapeutic effect are presented in Tables 1, 2 and 3, in the Detailed Description of the Invention below.
  • the subject invention further provides preparing the pharmaceutical compositions disclosed herein comprising one or more synthesized isolated compounds and/or ingredients.
  • the herbal compositions and pharmaceutical compounds may be administered at least once a day.
  • compositions and compounds are administered twice or three times daily, based upon the condition of the subject.
  • the compositions and compounds may be administered as a beverage, capsule, tablet, powder, syrup, candy, gel, nutritional product, or pharmaceutical product.
  • the compositions and compounds may be further mixed with excipients as is known to those of skill in the art, many of which are listed in Chapter 36 of “Remington Essentials of Pharmaceutics” (Felton, L. (Ed.) 2013, pp. 683-704).
  • a pharmaceutical composition prepared from extracts of the plants has demonstrated effectiveness in treating COVID-19-positive subjects, as subjects treated with it have experienced non- progression of the disease, and quick disappearance of any symptoms.
  • FIG. 1 shows “classification of COVID-19 disease states and potential therapeutic targets. The figure illustrates 3 escalating phases of COVID-19 disease progression, with associated signs, symptoms, and potential phase-specific therapies” (Siddiqi & Mehra, 2020, March 20). DETAILED DESCRIPTION OF THE INVENTION Definitions "About”, as used herein, means in quantitative terms plus or minus 10%.
  • “Amelioration”, as used herein, of the symptoms of a particular disorder by administration of a particular composition refers to any lessening, whether permanent or temporary, lasting or transient that can be attributed to or associated with administration of the composition.
  • “Antigen test” in relation to COVID-19, as used herein, detects antibodies to SARS-CoV-2 in a subject.
  • Antiviral as used herein, refers to a substance or process that destroys a virus or suppresses replication (reproduction) of the virus.
  • “ARV” means “antiretroviral”, as used herein, refers to a substance or process that destroys a retrovirus or suppresses replication (reproduction) of the retrovirus, including HIV.
  • CD4+ T cell refers to an immune T cell which is involved in protecting against infectious agents including viral, fungal, and protozoal infectious agents.
  • the CD4 molecule is expressed on the surface of T helper cells, and serves as the primary target for HIV-1 and HIV-2.
  • CD4 is the co-receptor for the T cell receptor and recruits the tyrosine kinase 1 ck intracellularly. CD4 cell counts are reduced with the progression of HIV.
  • Combination refers to any association between or among two or more items. The combination can be two or more separate items, such as two compositions or two collections. It can be a mixture thereof, such as a single mixture of the two or more items, or any variation thereof.
  • Composition refers to any mixture. It can be, without limitation, a solution, a suspension, liquid, powder, a paste, aqueous, non-aqueous or any combination thereof; and may be presented, without limitation, as a beverage, capsule, tablet, powder, candy, gel, nutritional product, or pharmaceutical product.
  • COVID-19 refers to any infection, illness or syndrome, caused directly or indirectly by SARS-CoV-2, including asymptomatic infections.
  • Extract refers to a solution containing compound(s), usually in a concentrated form, obtained by treating a solid material (such as for example, plant material) with a solvent to remove desired compounds or components.
  • Extraction refers to a method of separation in which a solid or solution is contacted with a liquid solvent to transfer one or more components of the solid into the solvent.
  • Highly active antiretroviral therapy or HAART, as used herein, refers to treatment regimens designed to aggressively suppress viral replication and progress of HIV disease, usually consisting of three or more different drugs, such as for example, two nucleoside reverse transcriptase inhibitors and a protease inhibitor.
  • “Ingredient”, as used herein, refers to one or more materials used in the manufacture of a composition. Ingredient can refer to a pharmaceutically active ingredient or to other materials in the composition.
  • Ingredients can include, without limitation water, other solvents including non-aqueous solvents, salts, buffers, surfactants, excipients, and flavorings.
  • PCR test in relation to COVID-19, as used herein, refers to a test that measures the presence of genetic material from SARS- COV-2 in a subject.
  • “Pharmaceutical composition” refers to a composition that contains at least one pharmaceutically active ingredient, and one or more other pharmaceutically-acceptable ingredients, that is formulated for administration to a human subject.
  • “Pharmaceutically-acceptable”, as used herein, indicates that the identified material does not have properties that would cause a reasonably prudent medical practitioner to avoid administration of the material to a subject, taking into consideration the disease or conditions to be treated and the respective route of administration.
  • SARS-CoV-2 as used herein, means the virus that causes the Novel Coronavirus Disease of 2019 (COVID-19), inclusive of all of its variants.
  • “Synthesized alkaloid compounds”, as used herein, refers to alkaloid compounds obtained by chemical synthesis.
  • “Synthesized steroid glycoside compounds”, as used herein, refers to steroid glycoside compounds obtained by chemical synthesis.
  • “Synthesized terpenoid compounds”, as used herein, refers to terpenoid compounds obtained by chemical synthesis.
  • “Therapeutically effective” or “effective amount”, as used herein, indicates that the materials or amount of material is effective to prevent, alleviate, or ameliorate one or more symptoms of a disease or medical condition, and/or to prolong the survival of the subject being treated.
  • “Treatment”, as used herein, refers any manner in which the symptoms of a condition, disorder or disease or other indication, are ameliorated or otherwise beneficially altered.
  • “Viral load test” in relation to HIV, as used herein, refers to a test that measures the quantity of HIV RNA in the blood, expressed as number of copies per mL of blood plasma. Discussion The present invention relates to the discovery that combinations of plants native to Kenya can be used in the treatment of COVID- 19.
  • compositions of the present invention are particularly well suited for the treatment of COVID-19.
  • Compositions of the invention can be prepared from plant material collected from the Mau Forest Complex in Western Kenya.
  • Herbal compositions prepared from aqueous extractions and purified extracts of plants from this region of Kenya exhibit increased potency in the treatment of infectious diseases.
  • the Mau Forest Complex is located at 0 degrees, 30' South, 35 degrees, 20' East and in the Rift Valley Republic, and spans four Kenyan administrative districts: Narok, Nakuru, Bomet and Kericho.
  • Mean annual rainfall varies from 1000 to 1500 mm with peaks in April and August. The rainfall pattern at the eastern flanks is governed by the moist monsoon winds from the Indian Ocean and dry winds from the Great Rift Valley.
  • the western flanks of the Mau Forest Complex are influenced by the Lake Victoria macroclimatic region, and are generally wetter, with annual rainfall greater than 2000 mm, and it is more evenly distributed.
  • Mean annual temperatures for the Mau Forest Complex range from 12-16 degrees C.
  • the soil of the Mau Forest Complex is rich volcanic loam having a pH between 3.8-5.8.
  • the vegetational pattern follows an altitudinal gradient with local topographical ecolines.
  • the closed canopy moist mountain forest at lower altitudes becomes increasingly intermixed with bamboo from 2200 m onwards. Between 2300 and 2500 m, pure bamboo (Arundinaria alpina) swards are found.
  • plants of the Western flank have more biosynthetic pathways, which may in turn lead to the production of a greater number of diverse compounds, which may in turn explain the greater potency of plants from the Western flank (as compared to other regions of the Mau Forest Complex).
  • the greater potency plant extracts from the Western flank plants may be a result of a greater variety and number of alkaloids and other compounds in the plant extracts, such that the combined effect is greater than the sum of their individual effects.
  • the East Mau Forest Complex has a drier vegetation of cedar and podo. Wherever these species have been identified, colonizing species such as Neuboutonia marcrocalyx and Macaranga capensis can be found.
  • compositions of the invention may be prepared using plants collected from three altitude ranges of the Mau Forest Complex: 2000 m above sea level (annual rainfall of 1000 mm), 2300 m above sea level (annual rainfall 1500 mm), and 2500 m above sea level (the Western Mau flank, annual rainfall greater than 2000 mm).
  • the Western flanks of the Mau Forest contain plants that are particularly preferred for preparing the herbal compositions of the invention.
  • the plants grown in the drier Eastern flank of the Mau Forest Complex also may be used.
  • Plant material for preparing compositions of the invention may also be obtained from plants grown in a greenhouse environment. The germination of the seeds of particular plants may be altitude or soil dependent. Seeds for greenhouse planting may require collection from the natural dispersal agents as they exist in the wild.
  • the seeds of Dovyalis abyssinica (representative seed of said line having been deposited under ATCC Accession No. PTA-6969) are contained in a fleshy fruit. There are about 4 seeds enclosed by the flesh. A ripe fleshy fruit can be soaked in water for about 4 days, to make it possible to squeeze with minimum force to release the small seeds, each being approximately the size of a tomato seed or slightly larger. The seeds are then washed, dried and stored, awaiting germination under Mau Forest-like environmental conditions.
  • the berries should be placed in a metallic container, and covered with a material that allows sunlight to enter, such as a transparent polyethylene film surrounding a container of appropriate wire mesh. Exposure to light will cause the shells to break open, releasing the seeds which can then be separated from the chaff.
  • the optimal time for planting the Clutia robusta and Dovyallis abyssinca seeds in their natural environment is during the long rains, typically around the month of April. However, in the wild, the plants will generally grow throughout the year, except during the dry season, as the plants require a considerable amount of water and light to grow.
  • Croton macrostachyus produces pale pea-sized capsules, on drooping spikes to 30 cm long, splitting open on the tree to release 3 shiny grey seeds, covered at one end by a soft, creamy aril, or envelope.
  • Prunus Africans produces spherical fruit, about 10 mm in diameter which is pinkish brown in color.
  • the Acacia nilotica (representative seed of said line having been deposited under ATCC Accession No. PTA-7378) plant produces straight or curved pods measuring approximately 17 by 2 cm. When young, the pods are green and fleshy, but they get darker with age, and are usually velvety. Pods have a fruity odor and open on the ground to release seeds.
  • Ekebergia capensis produces rounded, thin skinned berries, up to 2.5 cm in diameter, on long stalks in heavy bunches, which are yellow to red in color when mature.
  • the berry-like fruits of Rhamnus prinoides are approximately the size of a pea (about 5 mm in diameter), roundish and clearly divided into three compartments. They are fleshy and green, turning red and then purple as they ripen.
  • the fruit of the Asparagus africanus is a round berry, approximately 0.5 cm in diameter, green aging to orange, found most of the year. It is spread mainly by birds carrying the seeds.
  • the Anthocleista grandiflora produces fruits that are oval in shape, measuring approximately 3 cm. by .2 cm, glossy, smooth and brown when mature.
  • the Bersama abyssinica produces a smooth, spherical capsule, measuring approximately 2.5 cm in diameter, golden velvety at first, losing most of the hair and becoming brown by maturity; splitting into four valves to reveal attractive bright red seeds, about 10 mm long, enveloped for about half of their length by a yellow, cup-shaped aril.
  • Adenia gummifera produces a fruit which is a stalked 3-valved capsule, leathery or fleshy, often red; seeds are compressed with bony testa in a fleshy aril.
  • Plantago palmata (representative seed of said line having been deposited under ATCC Accession No. PTA-7377) produces a capsule- like fruit with two seeds per capsule.
  • Periploca linearifolia (representative seed of said line having been deposited under ATCC Accession No. PTA-7375) produces black seeds measuring approximately 10 mm long and 2 mm wide with white wool measuring around 3 cm attached to the tips of the seeds. The seeds are enclosed in pods measuring about 12 cm long. Upon maturity, the pods break open upon exposure to sunlight. This releases the seeds, which are borne aloft by the wool as they are dispersed by wind. Alternatively, these plants may be cultivated from stem cuttings, which when laid on or planted in the ground, grow roots, and propagate new plants. Clematis hirsuta (representative seed of said line having been deposited under ATCC Accession No.
  • PTA-7383 produces yellowish seeds measuring approximately 3 mm in length and 1 mm in breadth. The seeds are surrounded by yellowish-white wool which measures about 5 mm long. The wool carries the seeds upon the wind, which is the dispersal agent. Based on our finding that certain combinations of certain plant material are effective treatments for COVID-19, certain compounds thought to be active have been isolated from each plant.
  • the following plant material was used: dried root of Dovyalis abyssinica, dried root of Clutia robusta, dried stem bark of Prunus Africana, dried stem bark of Croton macrostachyus, dried stem bark of Acacia nilotica, dried root of Rhamnus prinoides, dried root of Adenia gummifera, dried root of Asparagus africanus, dried stem bark of Anthocleista grandiflora, dried whole plant of Plantago palmata, dried root of Clematis hirsuta, dried stem bark of Ekebergia capensis, dried stem bark of Bersama abyssinica, and dried root of Periploca linearifolia.
  • the preferred weight ratio of the aforementioned plant material is 2:2:2:2:2:1:2:2:1:2:2:2:2:2, respectively, and each was chopped into small parts, dried and mixed into a herbal mixture. Other weight ratios can also be used.
  • the alkaloids specified in Table 1 were isolated from the plant material by first grinding each individual herb. Then, base was added to obtain a basic solution and said mixture was heated. Sufficient base is added to the defatted herbal material to achieve a pH of approximately 8. The concentration of the base added can be adjusted to provide sufficient liquid volume to cover the defatted herbal solid mixture.
  • any suitable base may be used, with preferred bases including NaOH, KOH, Ca(OH) 2 , Mg(OH) 2 , NH 4 OH, and the like.
  • the base extract is then heated for 2-4 hours.
  • the ingredients are slowly simmered under reflux conditions, although the same effect can be achieved by simmering the mixture in a covered pot.
  • acid was added to obtain an acidic solution, and said solution was heated.
  • the acid was aqueous HCl and the pH of the acidic solution was about 3.
  • the acid is HCl, although other acids, including but not limited to, HBr, HNO 3 , H 2 SO 4 , H 3 PO 4 , or any other acid suitable for achieving a pH of approximately 3 may be used as well.
  • the concentration of the acid can be adjusted as necessary to provide sufficient volume to the mixture.
  • the acidified solution is then boiled for approximately 2-4 hours under the same conditions employed for the heating of the basic solution. After heating, the mixture is cooled, and the aqueous layer is separated from the mixture, such as for example, by decanting the liquid from the remaining solids. Acid is then added to the remaining residue sufficient to achieve a pH of approximately 3, and the mixture is then reheated for approximately 2-4 hours under the same conditions previously employed. The aqueous layer is separated from the ingredients and the two acidified layers are combined. If necessary, additional acid extractions may be performed.
  • the acidic solution was decanted to provide an acidic extract and a residue, acid was added to the residue and the acid and residue were heated at a simmer for about four hours.
  • the acid was aqueous HCl.
  • other extractive treatments by heat or otherwise, could be used, and are within the scope of this invention.
  • ethanol can be used as a solvent in some extractive processes.
  • Alkaloids were extracted from said acidic solution with a non- polar solvent, e.g. ether.
  • Non-polar solvents are generally organic solvents having a dielectric constant less than 20.
  • Non-polar solvents that may be used include, but are not limited to: alkanes, 1,4-dioxane, carbon tetrachloride, chloroform, methylene chloride, benzene, ethers, ethyl acetate, tetrahydrofuran, acetic acid, butanol, chlorobenzene, cycloalkanes, xylene, and the like.
  • Preferred non-polar solvents are xylene and ether.
  • the non-polar solvent added was about 20% by volume. However, other volume percentages could be used, and are within the scope of this invention.
  • the alkaloids were precipitated and collected at a pH of about 9 to isolate the alkaloids.
  • precipitative treatments and/or other PH levels, could be used, and are within the scope of this invention.
  • methods of extraction known to those of skill in the art, or which may come to be known by them, could be used, and are within the scope of this invention.
  • the precipitated alkaloid mixtures from each of the 14 plants were subjected to repeated column chromatography. Silica gel was used as a stationary phase. However, other stationary phases could be used, and are within the scope of this invention.
  • the column was first eluted with n-hexane, followed by varying proportions of ethyl acetate, until 100% ethyl acetate was added. The column was finally washed with methanol.
  • the alkaloid compounds in a plant are thought to be among the active compounds in the plant. That is, the alkaloid compounds isolated from each plant set forth in Table 1 have at least analogous activity to the extracts.
  • terpenoids are known to be pharmacologically active in some cases. When terpenes are modified chemically, such as by oxidation or rearrangement of the carbon skeleton, the resulting compounds are generally referred to as terpenoids. Some authors will use the term terpene to include all terpenoids. Terpenoids are also known as isoprenoids. Terpenoid compounds were serially extracted from the relevant chopped and ground parts of each plant.
  • steroid glycosides are known to be pharmacologically active in some cases.
  • a method of isolating steroid glycosides is as follows. Chopped plant materials were coarsely powdered and extracted in a Soxhlet apparatus with chloroform for 12 hours. The chloroform extract can be concentrated to obtain a dark viscous mass. A small amount of the extract was screened chemically for determination of different phytoconstituents. The concentrated extract was dissolved in small quantity of chloroform and adsorbed on silica gel (60-120 mesh) for preparation of slurry. The slurry was then air-dried and chromatographed over a silica gel column.
  • the column was eluted with chloroform-ethyl acetate (8:2, v/v). The chromatograms were then developed in an iodine chamber. The fractions were collected separately and matched by thin layer chromatography (TLC) to check their homogeneity. The fractions with the same retention factor (Rf) value were combined together and crystallized. The compound was then recrystallized with methanol and finally purified by preparative thin layer chromatography (TLC). The isolated compound was subjected to spectral and chemical studies for characterization. Other methods of extraction and elucidation which are available now or which may come to be available in the future could be used, and are within the scope of this invention.
  • the steroid glycosides isolated and elucidated by applicants have been set forth in Table 3. They are thought to comprise a portion of the synergistic effect of the invention. Other methods of extraction and elucidation which are available now or which may come to be available in the future could be used, and are within the scope of this invention. Ethanol can be used in some extractive processes, alone, or in combination with water in hydroethanolic extraction. Many other methods of extraction and elucidation are known in the art.
  • One or more of the isolated compounds set forth in tables 1, 2 and 3 below may be synthesized according to methods which are known or will occur to those skilled in the art, and may be therapeutically administered, or comprised in any composition or pharmaceutical composition of the invention.
  • compositions having the disclosed compounds were tested against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus).
  • the specific compositions were in the form of plant extracts. Solutions containing 100 ppm (parts per million) of each plant extract were prepared for use in the anti-bacterial assay. Preparation of bacterial culture of E. coli and S. aureus Standard cultures of E. coli (representing gram-negative strains of bacteria) and S.
  • aureus (representing gram-positive bacteria) were obtained from Moi University Teaching and Referral Hospital. Assays were conducted at the Moi University Department of Botany in Eldoret, Kenya. Nutrient agar was used as growth medium for both bacteria samples. The agar was sterilized in an autoclave at 120°C, cooled and poured into sterile Petri dishes and allowed to set. Sterile conditions were achieved and maintained by exposing the area to a UV lamp during sample preparation and the assay procedure. The cooled agar medium was streaked on the surface with each bacteria culture. Wells were dug in the middle of the medium, using a cork borer, where the prepared plant extract was deposited. A control experiment was also performed, using plain sterile water in place of the plant extracts.
  • Table 4 Inhibition Diameters HIV/AIDS therapy with the instant invention Preparation of the compositions of the invention for treating HIV/AIDS
  • the compositions and compounds that were used in the Examples below were prepared and isolated from the roots of Dovyalis abyssinica and Clutia robusta, and optionally one or more of the following: the stem bark of Prunus africana, stem bark of Croton macrostachyus, stem bark of Acacia nilotica, roots of Rhamnus prinoides, roots of Adenia gummifera, roots of Asparagus africanus, stem bark of Anthocleista grandiflora, whole plant of Plantago palmata, roots of Clematis hirsuta, stem bark of Ekebergia capensis, stem bark of Bersama abyssinica, and roots of Periploca linearifolia.
  • the ingredients collected are fresh, although dried samples may also be used.
  • the ingredients are combined and chopped into small pieces and dried.
  • the compounds can be used in the following weight ratio, by reference to the plant from which they are isolated: Dovyalis abyssinica, Clutia robusta, Prunus africana, Croton macrostachyus, Acacia nilotica, Rhamnus prunioides, Adenia gummifera, Asparagus africanus, Anthocleista grandiflora, Plantago palmata, Clematis hirsuta, Ekebergia capensis, Bersama abyssinica and Periploca linearifolia, in a weight ratio of 2:2:2:2:2:1:2:2:1:2:2:2:2, respectively.
  • the plant extract precipitates are preferably purified and collected in either crystalline, paste or powder form.
  • the precipitates can be administered to a subject as a beverage, capsule, tablet, powder, candy, gel, nutritional product, pharmaceutical product, or other form.
  • the amounts for administration may vary and may be readily determined by those of skill in the art. For example, the amount may be from 0 to about 50 grams, from about 0.5 grams to about 35 grams, from about 0.1 and 25 grams, from about 0.1 to about 10 grams, or from about 0.1 grams to about 5 grams of alkaloids, distributed in whatever composition form, are administered per day to an infected subject.
  • the herbal composition is administered as a beverage wherein approximately 1 tbsp of powdered extract is dissolved in approximately 250 mL of hot water, and drunk.
  • Other amounts and volumes will be recognized by those of skill in the art. Dosing is either twice daily at 12-hour intervals, or three times daily at eight-hour intervals (depending on the level of infection of the test subject), and is preferably administered with a meal. Other dose regimens are also possible.
  • Subjects and experimental design Subjects in the Examples below were screened at the Walter Reed Hospital of the U.S. Army in Kericho, the Moi University Hospital in Eldoret, and at various Voluntary Counseling and Testing (VCT) Centers scattered throughout the country of Kenya.
  • CD4 and CD8 counts were measured using a FACSCountTM system following procedures provided in the FACSCount White Paper (July 1994). HIV-1 and HIV-2 antibodies were detected using a bioMerieux Vironostika® HIV Uni-Form II Ag/Ab ELISA system. All subjects administered the herbal composition were HIV- positive adults. Prior to administration of the herbal composition, an initial CD4 count for each subject was determined, followed by an assessment of the level of opportunistic infections. Those with fewer opportunistic infections were administered the herbal composition twice daily after meals, at 12-hour intervals. Those with more opportunistic infections were administered the herbal composition three times daily, at 8 hours intervals. Each subject was given one week's dosage during each visit to the clinic.
  • Example 1 Initial studies for the treatment of HIV positive subjects with the herbal remedy were conducted by treating four HIV-positive subjects with two different herbal remedies. Two subjects were administered a herbal composition which included the extract of Dovyalis abyssinica, while the other two subjects were administered a herbal remedy which included the extract of Clutia robusta. The subjects were each treated for a period of three months. The CD4 counts of both sets of subjects (i.e., those administered either Dovyalis abyssinica or Clutia robusta) increased by approximately 10 per month of treatment.
  • Example 2 In another study, three subjects were administered a herbal composition prepared with a 1:1 ratio by weight mixture of Dovyalis abyssinica and Clutia robusta, for a period of approximately three months.
  • the CD4 counts of the subjects treated with the mixture increased by approximately 30 per month, demonstrating a synergistic effect of the combination.
  • the CD4 counts of the subjects treated with the combination increased by an amount greater than the sum of the increases in the CD4 counts of the patients treated with the individual ingredients.
  • Example 3 In yet another experiment, 20 subjects were administered a herbal composition containing extracts of Dovyalis abyssinica, Clutia robusta, Prunus Africana, Croton macrostachyus, Acacia nilotica, Ekebergia capensis, Clematis hirsuta and Adenia gummifera.
  • the 8 plant extracts were selected from the aforesaid 23 total plant extracts which had been previously assayed against E. coli and S. aureus.
  • CD4 counts of subjects increased by up to 100 per month, but none of the subjects tested HIV negative within the three-month period. An enhanced synergistic effect was demonstrated by the 8-herb combination.
  • Table 5 CD4 Counts per Month Example 4
  • 26 HIV-positive subjects were treated with a herbal composition consisting of the 14 herbal ingredients identified in Table 4.
  • Subjects were administered a composition prepared by dissolving approximately 1 tbsp. (or 15 ml.) of the powdered ingredients (a mixture prepared with the 14 plants listed in Table 4) in approximately 8 ozs. (250 ml) of hot water. The supernatant liquid was then ingested by the subject.
  • the subjects were divided into two groups: the first group having 10 subjects (subject ID Nos. 1-10) and the second group having 16 subjects (Subject ID Nos. 11-26). In the first group, each of the 14 plants was present in the composition in equal weight ratios.
  • the concentrations of Dovyalis abyssinica and Clutia robusta were approximately half of the other 12 ingredients as disclosed.
  • CD4 counts for each subject were measured on a monthly basis.
  • the CD4 counts of the test subjects treated with the 14-ingredient herbal composition increased by up to 100 per month.
  • the 14-herb combination therapy displayed a level of ameliorative synergy that has never been demonstrated in any HAART combination therapy, in that some of the subjects in sero- reversed and became HIV-negative.
  • ARV regimes include treatment with combinations consisting of ZDV-3TC-NVP, d4T-3TC-EFV and ZDV-3TC-EFV (wherein ZDV is Zidovudine and EFV is Efavirenz).
  • Treatment guidelines are provided in the publication “Integrated Management of Adolescent and Adult Illness,” published in January 2004 by the World Health Organization. ARV therapy subjects are not known to reverse their seroconversion status, and among those listed in Table 7, none did so.
  • Table 7 Results of CD4 Count Increases in Subjects Under Conventional ARV Therapy at Moi University; For Comparison With Those Achieved With the Instant Invention The herbal composition was approved as complementary medicine No.
  • the extract was obtained from two successive two-hour heated decoctions of the same 100 gm. of dried powdered herbal composition in 3 liters of fresh solvent mixture each time, said solvent mixture containing 5 parts water to 1 one part ethanol, at a temperature slightly below boiling.
  • the undissolved residue of the said 100 gm. of said dried powdered herbal composition that had been used for the two decoctions was removed from the solution by filtration, and discarded.
  • the resultant filtered solution was compounded and solidified with 300 gm. each of hydroxyethyl cellulose and corn starch, and 11.25 gm. of magnesium stearate.
  • each capsule administered to a patient contains approximately 22 mg. of dried powdered hydroethanolic herbal extract.
  • the hydroethanolic extraction method was chosen by applicants as a way to increase the amount terpenoid compounds present in the extract, because terpenoids are not hydrophilic and are underrepresented in an aqueous extract.
  • COVID-19 symptomatology is staged as: 1) asymptomatic or pre-symptomatic; 2) mild; 3) moderate; 4) severe; and 5) critical.
  • Detailed discussion of COVID-19 stages and their associated symptoms is given, inter alia, at National Institutes of Health, 2021, October 19; Lowth, M. (Patient, 2020, April 20; and Jarvis (Patient, 2021, December 1).
  • any composition comprised of any part or parts of the recited plants which includes Dovyalis abyssinica and Clutia robusta is within the scope of the invention. It is understood by those skilled in the art that the identity of the most bioactive compounds in a botanical therapeutic can unpredictable, and the dynamics of the therapeutic synergy difficult to analyze (Ruiz et. al, 2016, July 26). Therefore, the presence of all of the isolated compounds may not be necessary in a therapeutically-effective pharmaceutical composition, and such compositions containing less than all of applicants’ isolated compounds are within the scope of the invention.

Abstract

Compositions of and compounds found in combinations of up to 14 Kenyan plants, including Dovyalis abyssinica and Clutia robusta, are provided for treatment of COVID-19.

Description

COMPOSITIONS AND COMPOUNDS FOR TREATING COVID-19 References U.S. PATENT DOCUMENTS US 7,556,830 B2 7/2009 Chepkwony et al. ……… 424/725 US 7,647,483 B2 3/2010 Chepkwony et al. ……… 424/725 US 8,053,802 B2 11/2011 Chepkwony et al. ……… 424/725 US 8,067,401 B2 11/2011 Chepkwony et al. ……… 424/725 US 8,404,284 B2 3/2013 Medina et al. ……………… 514/176 US 8,697,660 B2 4/2014 Chepkwony et al. ……… 514/26 US 10,695,361 B26/2020 Clarke et. al. ……. A61K 31/7056 OTHER PATENT DOCUMENTS WO 2007/024510 A27/2007 Chepkwony et al. ………. A61K 36/736 ZA 011/9418 8/2012 Medina et al. ……………. A61K 36/47 KE 00552 9/2012 Chepkwony et al ………. A61K 36/00 EP 1,919,490 B1 3/2014 Chepkwony et. al. ……… A61K 36/00 JP 5,469,862 2/2014 Chepkwony et al. ……… A61K 36/18 OTHER PUBLICATIONS Ahmad, S., Zahiruddin, S., Parveen, B., Basist, P., Parveen, P., Gaurav, Parveen, R. & Ahmad, M. (2021, March 2). Indian medicinal plants and formulations and their potential against COVID-19 – preclinical and clinical research. Frontiers in Pharmacology 11:578970. https://doi.org/10.3389/fphar.2020.578970 Angeles-Agdeppa, I., Nacis, J., Capanzana, M., Fabian M., Dayrit, M., Tanda, K. (2021, May 24). Virgin coconut oil is effective in lowering C-reactive protein levels among suspect and probable cases of COVID-19 Journal of Functional Foods 83 (2021):104557. https://doi.org/10.1016/j.jff.2021.104557 Ai, Z., Zhou, S., Li, W., Wang, M., Wang, L., Hu, G., Tao, R., Wang, X., Shen, Y., Xie, L., Ba, Y., Wu, H. & Yang, Y. (2020, October 8). “Fei Yan No. 1” as a combined treatment for COVID-19: an efficacy and potential mechanistic study. Frontiers in Pharmacology 11:581277. https://doi.org/10.3389/fphar.2020.581277 AlNajrany, S.M., Asiri, Y., Sales, I. & AlRuthia, Y. (2021, April 28). The commonly utilized natural products during the COVID-19 pandemic in Saudi Arabia: a cross-sectional online survey. International Journal of Environmental Research and Public Health 2021(18):4688. https://doi.org/10.3390/ijerph18094688 1. Amuka, O., Okemo, P., Machocho, A., & Mbugua, P. (2014, November 28). Ethnobotanical survey of selected medicinal plants used by Ogiek communities in Kenya against microbial infections. Ethnobotany Research & Applications 12:627-641. https://doi.org/10.17348/era.12.0.627-641 Attah, A.F., Fagbemi, A.A., Olubiyi, O., Dada-Adegbola, H., Oluwadotun, A., Elujoba, A. & Babalola, C.P. (2021, April 26). Therapeutic potentials of antiviral plants used in traditional African medicine with COVID-19 in focus: a Nigerian perspective. Frontiers in Pharmacology 12:596855. https://doi.org/10.3389/fphar.2021.596855 Ayatollahi, S.A., Sharifi-Rad, J., Fokou, P.V.T., Mahady, G.B., Ansar Rasul Suleria, A.R., Kapuganti, S., Gadhave, K., Giri, R., Garg, N., Sharma, R., Ribeiro, D., Rodrigues, C.F., Reiner, Z., Taheri, Y. & Cruz-Martins N. (2021, June 25). Naturally occurring bioactives as antivirals: emphasis on coronavirus infection. Frontiers in Pharmacology 12:575877. https://doi.org/10.3389/fphar.2021.575877 Bahramsoltani R., & Rahimi R. (2020, November 25). An evaluation of traditional Persian medicine for the management of SARS-CoV-2. Frontiers in Pharmacology 11:571434. https://doi.org/10.3389/fphar.2020.571434 Benarba, B., & Pandiella, A. (2020, August 7). Medicinal plants as sources of active molecules against COVID-19. Frontiers in Pharmacology 11:1189. https://doi.org/10.3389/fphar.2020.01189 2. Bally, P.R.O. (1946, December 1). Coryndon museum expedition to the Mau forest. Journal of the East African Natural History Society XIX(3&4). 3. I. A botanist’s journey, pp. 81-91. https://journals.co.za/doi/10.10520/AJA19376812_498 4. IV. Plants collected on the expedition, pp. 95-100. https://journals.co.za/doi/10.10520/AJA19376812_501 5. 6. 7. Brahmbhatt, B. (2021, January 23). Herbal medicines in management and prevention of coronavirus disease 2019 (COVID-19). American Journal of Phytomedicine and Clinical Therapeutics 9(1:3). https://www.imedpub.com/articles/herbal-medicines-in- management-and-prevention-of-coronavirus-disease-2019- covid19.pdf of Phytomedicine and Clinical Carmona, F. & Pereira, A. (2013, March-April). Herbal medicines: old and new concepts, truths and misunderstandings. Revista Brasileira de Farmacognosia Brazilian Journal of Pharmacognosy 23(2), pp. 379- 385. https://doi.org/10.1590/S0102-695X2013005000018 Cele, S., Karim, F., Lustig, G., San, J., Hermanus, T., Tegally, H., Snyman, J., Moyo-Gwete, T., Wilkinson, E., Bernstein, M., Khan, K., Hwa, S.-H., Tilles, S., Singh, L., Giandhari, J., Mthabela, N., Mazibuko, M., Ganga, Y., …. Sigal, A. (2021, December 7). SARS- CoV-2 evolved during advanced HIV disease immunosuppression has Beta-like escape of vaccine and Delta infection elicited immunity. medRxiv preprint. https://doi.org/10.1101/2021.09.14.21263564 Chen R.H., Yang L.J., Hamdoun S., Chung S.K., Lam C.W., Zhang K.X., Guo X., Xia C., Law B.Y.K. & Wong V.K.W. (2021, March 4) 1,2,3,4,6- pentagalloyl glucose, a RBD-ACE2 binding inhibitor to prevent SARSCoV-2 infection. Frontiers in Pharmacology 12:634176. https://doi.org/10.3389/fphar.2021.634176 Chen, X., Wu, Y., Chen, C., Gu, Y., Zhu, C., Wang, S., Chen, J., Zhang, L., Lv, L., Zhang, G., Yuan, Y., Chai, Y., Zhu, M. & Wu, C. (2021). Identifying potential anti-COVID-19 pharmacological components of traditional Chinese medicine Lianhuaqingwen capsule based on human exposure and ACE2 biochromatography screening. Acta Pharmaceutica Sinica B 2021;11(1), pp. 222-236. https://doi.org/10.1016/j.apsb.2020.10.002 Cohen, J. & Piller, C, (2020, May 13). E-mails offer look into charges of cronyism behind potential COVID-19 drug. Science. https://www.science.org/content/article/emails-offer-look- whistleblower-charges-cronyism-behind-potential-covid-19-drug COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health, (2021, May 21). https://www.covid19treatmentguidelines.nih.gov/ 8. Discovery Health, (2021, December 14). Discovery Health, South Africa’s largest private health insurance administrator, releases at- scale, real-world analysis of Omicron outbreak based on 211000 COVID-19 test results in South Africa, including collaboration with the South Africa. https://www.discovery.co.za/corporate/news- room Fakhri S., Piri S., Majnooni, M.B., Farzaei, M.H. & Echeverría, J. (2021, January 20). Targeting neurological manifestations of coronaviruses by candidate phytochemicals: a mechanistic approach. Frontiers in Pharmacology 11:621099. https://doi.org/10.3389/fphar.2020.621099 Felton, L. (Ed.) (2013). Remington Essentials of Pharmaceutics. Pharmaceutical Press. https://health.sbmu.ac.ir/uploads/Remington_Essentials_of_Pharma ceutics_-_Felton,_Linda.pdf Ferguson, N., Ghani, A., Cori, A., Hogan, A., Hinsley, W. & Volz, E. (2021, December 16). Report 49: Growth, population distribution and immune escape of Omicron in England. WHO Collaborating Centre for Infectious Disease Modelling; MRC Centre for Global Infectious Disease Analysis, Jameel Institute, Imperial College London. https://doi.org/10.25561/93038 Fitzgerald, M., Heinrich, M. & Booker, A. (2020, January 9). Medicinal plant analysis: A historical and regional discussion of emergent complex techniques. Frontiers in Pharmacology 10:1480. https://doi.org/10.3389/fphar.2019.01480 Ge, C. & He, Y. (2020, September 16). In silico prediction of molecular targets of Astragaloside IV for alleviation of COVID-19 hyperinflammation by systems network pharmacology and bioinformatic gene expression analysis. Frontiers in Pharmacology 11:556984. https://doi.org/10.3389/fphar.2020.556984 Hemp, A. (1999). An ethnobotanical study on Mt. Kilimanjaro. Ecotropica 5(2), pp. 147-155. https://eref.uni-bayreuth.de/21587/ Hetrick, B., Yu, D., Olanrewaju, A., Chilin, L., He, S., Dabbagh, D., Alluhaibi, G., Ma, Y.-C., Hofmann, L., Hakami, R. & Wu. Y. (2021, May 29). A traditional medicine, respiratory detox shot (RDS), inhibits the infection of SARS‑CoV, SARS‑CoV‑2, and the influenza A virus in vitro. Cell & Bioscience 11 (2021):100. https://doi.org/10.1186/s13578- 021-00609-1 Huang J., Tao G., Liu J., Cai J., Huang Z. & and Chen J.-X (2020, October 20). Current prevention of COVID-19: natural products and herbal medicine. Frontiers in Pharmacology 11:588508. https://doi.org/10.3389/fphar.2020.588508 Iheagwam, F. & Rotimi, S. (2020, September 14). Computer-aided analysis of multiple SARS-CoV-2 therapeutic targets: identification of potent molecules from African medicinal plants. Hindawi Scientifica 2020: 1878410. https://doi.org/10.1155/2020/1878410 9. Jarvis, S. (2021, December 1). Coronavirus: what are asymptomatic and mild COVID-19? Patient. https://patient.info/news-and-features/coronavirus-what-are- asymptomatic-and-mild-covid-19 Jha, N.K., Sharma, C., Hashiesh, H.M., Arunachalam, S., Meeran, M.F.N., Javed, H., Patil, C.R., Goyal, S.N., & Ojha, S. (2021, May 14). β-Caryophyllene, a natural dietary CB2 receptor selective cannabinoid can be a candidate to target the trinity of infection, immunity, and inflammation in COVID-19. Frontiers in Pharmacology 12:590201. https://doi.org/10.3389/fphar.2021.590201 Kalhori, M.R., Saadatpour, F., Arefian, E., Soleimani M., Farzaei, M.H., Aneva, I.Y. & Echeverría, J, (2021, February 23). The potential therapeutic effect of RNA interference and natural products on COVID-19: a review of the coronaviruses infection. Frontiers in Pharmacology 12:616993. https://doi.org/10.3389/fphar.2021.616993 Kamau, L., Mbaabu, P., Karuri, P., Mbaria. J. & Kiama, S. (2017, May 31). Medicinal plants used in the management of diabetes by traditional healers of Narok County, Kenya. TANG 7:2/e10 http://doi.org/10.5667/tang.2017.0008 Kifle, Z., Ayele, A., & Enyew, E. (2021, April 22). Drug repurposing approach, potential drugs, and novel drug targets for COVID-19 treatment. Journal of Environmental and Public Health Volume 2021:6631721. https://doi.org/10.1155/2021/6631721 Kigen, G., Kamuren, Z., Njiru, E., Wanjohi, B, & Kipkore, W. (2019, December 27). Ethnomedical survey of the plants used by traditional healers in Narok County, Kenya. Evidence-Based Complementary and Alternative Medicine 2019:8976937. https://doi.org/10.1155/2019/8976937 Kim, C.-H., (2021, May 27) Anti–SARS-CoV-2 natural products as potentially therapeutic agents. Frontiers in Pharmacology 12:590509. https://doi.org/10.3389/fphar.2021.590509 Kousar, K., Majeed, A., Yasmin, F., Hussain, W., & Rasool, N. (2020, October 13). Phytochemicals from selective plants have promising potential against SARS-CoV-2: investigation and corroboration through molecular docking, MD simulations, and quantum computations. BioMed Research International 2020:6237160. https://doi.org/10.1155/2020/6237160 10. Kozlov, M., Merck’s COVID pill loses its lustre: what that means for the pandemic (2021, December 12). Nature. https://www.nature.com/articles/d41586-021-03667-0 Lem, F.F., Opook, F., Lee, D.J.H., Chee, F.T., Lawson, F.P. & Chin, S.N. (2021, February 12). Molecular mechanism of action of repurposed drugs and traditional Chinese medicine used for the treatment of patients infected with COVID-19: a systematic scoping review. Frontiers in Pharmacology 11:585331. https://doi.org/10.3389/fphar.2020.585331 Li, L.-C., Zhang, Z.-H., Zhou, W.-C., Chen, J. Jin, H.Q., Fang, H.-M., Chen, Q., Jin, Y.-C., Qu, J. & Kan, L.D., (2020, August 19). Lianhua Qingwen prescription for coronavirus disease 2019 (COVID-19) treatment: advances and prospects. Biomedicine & Pharmacotherapy (2020),130: 110641). https://doi.org/10.1016/j.biopha.2020.110641 Li, Q., Bai, C., Yang, R., Xing, W., Pang, X., Wu, S., Liu S., Chen J., Liu, T. & Gu X (2020, November 26). Deciphering the pharmacological mechanisms of Ma Xing Shi Gan decoction against COVID-19 through integrating network pharmacology and experimental exploration. Frontiers in Pharmacology 11:581691. https://doi.org/10.3389/fphar.2020.581691 Liang, S.-B., Zhang, Y.-Y., Shen C., Liang, C.-H., Lai, B.-Y., Dai, N., Li, Y.-Q., Tian, Z.-Y., Zhang, X.-W., Jiang, Y., Xiong, M., Zhang, Y.-P., Zhang, Y., Robinson, N. & Liu, J.-P. (2021, February 26). Chinese herbal medicine used with or without conventional western therapy for COVID-19: an evidence review of clinical studies. Frontiers in Pharmacology 11:583450. https://doi.org/10.3389/fphar.2020.583450 Lim X.Y., Teh, B.P. & Tan, T.Y.C. (2021, March 24). Medicinal plants in COVID-19: potential and limitations. Frontiers in Pharmacology 12:611408. https://doi.org/10.3389/fphar.2021.611408 Liu, C., Zhou, Q., Li, Y., Garner, L., Watkins, S., Carter L., Smoot, J., Gregg, A., Daniels, A., Jervey, S. & Albaiu, D. (2020, March 6). Research and development on therapeutic agents and vaccines for COVID-19 and related human coronavirus diseases. American Chemical Society Central Science 2020, 6, 3, 315-331. https://doi.org/10.1021/acscentsci.0c00272 Liu, T. Guo, Y., Zhao, J., He, S., Bai, Y., Wang, N., Lin, Y., Liu, Q. & Xu, X. (2020, September 15). Systems pharmacology and verification of ShenFuHuang formula in zebrafish model reveal multi-scale treatment strategy for septic syndrome in COVID-19. Frontiers in Pharmacology 11:584057. https://doi.org/10.3389/fphar.2020.584057 11. Lowth, M. (2020, April 20). Coronavirus: what are moderate, severe and critical COVID-19? Patient. https://patient.info/news-and- features/coronavirus-what-are-moderate-severe-and-critical-covid- 19 Luo, C.-h., Ma, L.-l., Liu, H.-m., Liao, W., Xu, R.-c., Ci. Z.-m., Lin. J.-z., Han, L, & Zhang. D.-k. (2020, September 11). Research progress on main symptoms of novel coronavirus pneumonia improved by traditional Chinese medicine. Frontiers in Pharmacology 11:556885. https://doi.org/10.3389/fphar.2020.556885 Ma, L.L., Liu, H.M., Luo, C.H., He, Y.N., Wang, F., Huang, H.Z., Han, L., Yang, M., Xu, R.C. & Zhang, D.K. (2021, March 22). Fever and antipyretic supported by traditional Chinese medicine: a multi- pathway regulation. Frontiers in Pharmacology 12:583279. https://doi.org/10.3389/fphar.2021.583279 Majnooni M.B., Fakhri S., Shokoohinia Y., Kiyani N., Stage K., Mohammadi P., Gravandi, M.M., Farzaei, M.H. & Echeverría, J., (2020, November 28). Phytochemicals: potential therapeutic interventions against coronavirus-associated lung injury. Frontiers in Pharmacology 11:588467. https://doi.org/10.3389/fphar.2020.588467 Majeed, A., Hussain, W., Yasmin, F., Akhtar, A. & Rasool, N. (2021, May 21). Virtual screening of phytochemicals by targeting HR1 domain of SARS-CoV-2 S protein: molecular docking, molecular dynamics simulations, and DFT studies. BioMed Research International Volume 2021:6661191. https://doi.org/10.1155/2021/6661191 Supplementary 1: https://downloads.hindawi.com/journals/bmri/2021/6661191.f1.doc x Supplementary 2: https://downloads.hindawi.com/journals/bmri/2021/6661191.f2.doc x Supplementary 3: https://downloads.hindawi.com/journals/bmri/2021/6661191.f3.doc x Mandal, A., Jha, A.K. & Hazra, B., (2021, March 9). Plant products as inhibitors of coronavirus 3CL protease. Frontiers in Pharmacology 12:583387. https://doi.org/10.3389/fphar.2021.583387 Morrison, C. (2021, June 25). Countries that relied on Chinese vaccines see renewed COVID-19 surges. https://news.yahoo.com/countries- relied-chinese-vaccines-see-224000135.html Mbuni, Y., Wang, S., Mwangi, B. Ndungu J., Mbari, Musili, P., Walter, N., Hu, G., Zhou, Y. & Wang, Q. (2020, March 5). Medicinal plants and their traditional uses in local communities around Cherangani Hills, Western Kenya. Plants 9:331. https://doi.org/10.3390/plants9030331 Supplemental material: https://www.mdpi.com/2223- 7747/9/3/331/s1 Nankaya, J., Gichuki, N., Lukhoba, C., & Balslev, H. (2019, December 27). Medicinal plants of the Maasai of Kenya: a review. Plants 9:44. https://doi.org/10.3390/plants9010044 Supplemental material: http://www.mdpi.com/2223- 7747/9/1/44/s1 12. National Institutes of Health (2021, October 19), Clinical spectrum of SARS CoV-2 infection. https://www.covid19treatmentguidelines.nih.gov/overview/clinical- spectrum/ Nie, C., Trimpert, J., Moon, S., Haag, R., Gilmore, K., Kaufer, B., & Seeberger, P. (2021, February 15). In vitro efficacy of Artemisia extracts against SARS-CoV-2. bioRxiv preprint. https://doi.org/10.1101/2021.02.14.431122 Nugraha, R., Ridwansyah, H., Ghozali, M., Khairani, A., & Atik, N. (2020, October 10). Traditional herbal medicine candidates as complementary treatments for COVID-19: a review of their mechanisms, pros and cons. Evidence-Based Complementary and Alternative Medicine Volume 2020:2560645. https://doi.org/10.1155/2020/2560645 Nyang’au, H., Maingi, J & Kebira, A. (2017, January-February). The efficacy of some medicinal plants used locally within Transmara west, Narok County, Kenya against selected Enterobacteria and Candida. IOSR Journal of Pharmacy and Biological Sciences 12: Issue 1, Ver. I, pp. 115-122. https://doi.org/10.9790/3008- 120101115122 13. 14. Omara, T. (2020, June 12). Antimalarial plants used across Kenyan Communities. Evidence-Based Complementary and Alternative Medicine, 2020:4538602. https://doi.org/10.1155/2020/4538602 15. Orege, J., Adeyemi, S., Tiamiyu, B., Akinyemi, T., Ibrahim, Y., & Orege, O. (2021, May 5). Artemisia and Artemisia‑based products for COVID‑19 management: current state and future perspective. Advances in Traditional Medicine. https://doi.org/10.1007/s13596- 021-00576-5 16. Orisakwe, O., Orish, C. & Nwanaforo, E. (2020, October 28). Coronavirus disease (COVID-19) and Africa: acclaimed home remedies. Scientific African 10, (2020, November), e00620. https://doi.org/10.1016/j.sciaf.2020.e00620 17. Peter, A.E., Sandeep, B.V., Rao, B.G. & Kalpana, V.L. (2021, January 27). Calming the storm: natural immunosuppressants as adjuvants to target the cytokine storm in COVID-19. Frontiers in Pharmacology 11:583777. https://doi.org/10.3389/fphar.2020.583777 (1) Pfizer announces additional phase 2/3 study results confirming robust efficacy of novel COVID-19 oral antiviral treatment candidate in reducing risk of hospitalization or death (2021, December 14). https://www.pfizer.com/news/press-release/press-release- detail/pfizer-announces-additional-phase-23-study-results 18. (a) Philippines Food and Drug Administration (2021, April 5). DOH and FDA clarify claims on the approval of potential COVID-19 treatments and calls for resignation of the SOH. https://doh.gov.ph/doh-press-release/DOH-AND-FDA-CLARIFY- CLAIMS-ON-THE-APPROVAL-OF-POTENTIAL-COVID-19- TREATMENTS-AND-CALLS-FOR-RESIGNATION-OF-THE-SOH Philippines Food and Drug Administration (2021, April 20). Lianhua Qingwen Product Registration Certificate No. THPR-50. https://verification.fda.gov.ph/drug_productslist.php?cmd=search&t =drug_products&psearch=Lianhua+Qingwen&psearchtype= 19. 20. Prasad, A., Muthamilarasan, M. & Prasad, M. (2020, June 19). Synergistic antiviral effects against SARS‑CoV‑2 by plant‑based molecules. Plant Cell Reports 39 (2020, September), pp. 1109- 1114. 21. https://doi.org/10.1007/s00299-020-02560-w 22. Qiu, Q., Huang, Y., Liu, X., Huang, F., Li, X., Cui, L., Luo, H. & Luo, L. (2020, November 9). Potential therapeutic effect of traditional Chinese medicine on coronavirus disease 2019: a review. Frontiers in Pharmacology 11:570893. https://doi.org/10.3389/fphar.2020.570893 23. Remali, J. & Aizat, W.M. (2021, January 11). A review on plant bioactive compounds and their modes of action against coronavirus infection. Frontiers in Pharmacology 11:589044. https://doi.org/10.3389/fphar.2020.589044 Remdesivir. 2021, May 29. In Wikipedia. https://en.wikipedia.org/w/index.php? title=Remdesivir&oldid=1024312418 Ren, W., Ma, Y., Wang, R., Liang, P., Sun Q., Pu, Q., Dong, L., Mazhar, M., Luo, G. & Yang, S. (2021, January 27). Research advance on Qingfei Paidu decoction in prescription principle, mechanism analysis and clinical application. Frontiers in Pharmacology 11:589714. https://doi.org/10.3389/fphar.2020.589714 Republic of Kenya, Ministry of Health, Pharmacy and Poisons Board, Letter of July 21, 2014 Republic of Kenya, Ministry of Health, Pharmacy and Poisons Board, Invoice of December 9, 2020 24. Rigby, S. & Brown, W. (2021, November 26). Why scientists think the new variant may have emerged in an HIV patient. The Telegraph. https://www.telegraph.co.uk/global-health/science-and- disease/scientists-think-new-variant-may-have-emerged-hiv- patient/ Rotich, W., Sadgrove, N., Mas-Claret, E., Padilla-González, G., Guantai, A., & Langat, M. (2021, September 30). HIV-1 reverse transcriptase inhibition by major compounds in a Kenyan multi-herbal composition (CareVid™): in vitro and in silico contrast. Pharmaceuticals 2021, 14, 1009. https://doi.org/10.3390/ph14101009 Ruiz, G.G., Nelson, E.O., Kozin, A.F., Turner, T.C., Waters, R.F., & Langland, J.O. (2016, July 27). A lack of bioactive predictability for marker compounds commonly used for herbal medicine standardization. PLoS ONE 11(7):e0159857. https://doi.org/10.1371/journal.pone.0159857 Siddiqi, H.K. & Mehra, M.R. (2020, March 20). COVID-19 illness in native and immunosuppressed states: a clinical-therapeutic staging proposal. Journal of Heart and Lung Transplantation 39 (5), pp. 405-407. https://doi.org/10.1016/j.healun.2020.03.012 Silveira, D., Prieto-Garcia, J.M., Boylan, F., Estrada, O., Fonseca-Bazzo, Y.M., Jamal, C.M., Magalhães, P.O., Pereira, E.O., Tomczyk, M. & Heinrich, M. (2020, September 23). COVID-19: is there evidence for the use of herbal medicines as adjuvant symptomatic therapy? Frontiers in Pharmacology 11:581840. https://doi.org/10.3389/fphar.2020.581840 Songok, et al. (2015), Cell cytotoxicity testing of Kericho herbal compound. Republic of Kenya, Kenya Medical Research Institute. Spjut, R. (2005), Relationships between plant folklore and antitumor activity: an historical review. World Botanical Associates. Available at http://www.worldbotanical.com/images/ARS%20NCI%20Active%20 Plants/24_Spjut_Folklore-Antitumor_2205_2241.pdf Tuasha, Petros, B. & Asfaw, Z. (2018). Medicinal plants used by traditional healers to treat malignancies and other human ailments in Dalle District, Sidama Zone, Ethiopia. Journal of Ethnobiology and Ethnomedicine (2018) 14, 15. https://doi.org/10.1186/s13002-018- 0213-z U.S. Department of Agriculture, Agricultural Research Center (1980), List of plant species confirmed active, screened 6 or more times and GESOC. http://www.worldbotanical.com/images/slop.pdf U.S. Food and Drug Administration (2020, October 22). [Remdesivir] Emergency use authorization. https://www.gilead.com/- /media/files/pdfs/remdesivir/eua-fda-authorization- letter.pdf?la=en&hash=FD3737583BE0E4DF710ADB36AEAA2DBD Verma, S., Twilley, D., Esmear. T., Oosthuizen, C., Reid, A.-M., Nel, M. & Lall, N. (2020, September 25). Anti-SARS-CoV natural products with the potential to inhibit SARS-CoV-2 (COVID-19). Frontiers in Pharmacology 11:561334. https://doi.org/10.3389/fphar.2020.561334 Wang, F., Qu, M., Zhou, X, Zhao, K., Lai, C., Tang. Q, Xian, W., Chen. R., Li, X., Li, X., Li, Z., He, Q. & Liu, L. The timeline and risk factors of clinical progression of COVID-19 in Shenzhen, China (2020, July 3). Journal of Translational Medicine, 202018:270. https://doi.org/10.1186/s12967-020-02423-8 25. World Health Organization (2021, May 5) Coronavirus disease (COVID-19) advice for the public: Mythbusters ● Hydroxychloroquine https://www.who.int/images/default-source/health- topics/coronavirus/myth-busters/web- mythbusters/who_hydroxychloraquine_hd.jpg World Health Organization (2021, December 19). Global literature on coronavirus disease. https://search.bvsalud.org/global-literature- on-novel-coronavirus-2019- ncov/?output=site&lang=en&from=0&sort=&format=summary&cou nt=20&fb=&page=1&skfp=&index=tw&q=dovalis+or+clutia&search _form_submit= Accessed December 19, 2021. World Health Organization (2020, November 20). Therapeutics and COVID-19: living guideline. hdl:10665/336729. English version at http://apps.who.int/iris/bitstream/handle/10665/336729/WHO- 2019-nCov-remdesivir-2020.1- eng.pdf?sequence=1&isAllowed=yWHO/2019- nCov/remdesivir/2020.1 26. World Health Organization (2021, June 22) Weekly epidemiological update on COVID-19, Edition 45. https://www.who.int/publications/m/item/weekly-epidemiological- update-on-covid-19---22-june-2021 27. Wu, C.-Y., Lin, Y.-S., Yang, Y.-H., Shu, L.-H., Cheng Y.-C. & Liu, H.T. (2020, December 17). Potential simultaneous inhibitors of angiotensin-converting enzyme 2 and transmembrane protease, serine 2. Frontiers in Pharmacology 11:584158. https://doi.org/10.3389/fphar.2020.584158 28. Wu J., Sun B., Hou L., Guan F., Wang L., Cheng P., Scobell S., Cheng Y.- C. & Lam, W. (2021, February 25) Prospective: evolution of Chinese medicine to treat COVID-19 patients in China. Frontiers in Pharmacology 11:615287. https://doi.org/10.3389/fphar.2020.615287 Xi, S., Li, Y., Yue, L., Gong, Y., Qian, L., Liang, T. & Ye, Y. (2020, October 22). Role of traditional Chinese medicine in the management of viral pneumonia. Frontiers in Pharmacology 11:582322. https://doi.org/10.3389/fphar.2020.582322 29. Yang C.-W., Lee Y.-Z., Hsu H.-Y., Jan J.-T., Lin Y.-L., Chang S.-Y., Peng T.-T., Yang R.-B., Liang J.-J., Liao .C-C., Chao T.-L., Pang Y.-H., Kao H.-C., Huang W.-Z., Lin J.-H., Chang C.-P., Niu G.-H., Wu S.- H., Sytwu, H.-K., … & Lee S.-J. (2020, December 14). Inhibition of SARS-CoV-2 by highly potent broad-spectrum anti-coronaviral tylophorine-based derivatives. Frontiers in Pharmacology 11:606097. https://doi.org/10.3389/fphar.2020.606097 Zhang, X.-r., Li, T.-n., Ren, Y.-y., Zeng, Y.-j., Lv, H.-y., Wang, J. & Huang, Q.-w. (2020, September 25). The important role of volatile components from a traditional Chinese medicine Dayuan-Yin against the COVID-19 pandemic. Frontiers in Pharmacology 11:583651. https://doi.org/10.3389/fphar.2020.583651 Zhou Z., Gao, N., Wang, Y., Chang, P., Tong, Y. & Fu, S. (2020, September 10). Clinical studies on the treatment of novel coronavirus pneumonia with traditional Chinese medicine—a literature analysis. Frontiers in Pharmacology 11:560448. https://doi.org/10.3389/fphar.2020.560448 Zhang, L., Li, Q., Liang, Z., Li, T., Liu, S., Cui, Q., Nie, J., Wu, Q., Qu, X., Huang, W., & Wang, Y. (2021, December 10). The significant immune escape of pseudotyped SARS-CoV-2 Variant Omicron. Emerging Microbes & Infections. https://doi.org/10.1080/22221751.2021.2017757 Zhuang, W., Fan, Z., Chu, Y., Wang, H., Yang, Y., Wu, L., Sun, N., Sun G., Shen, Y., Lin, X., Guo, G. & Xi, S. (2020, July 17). Chinese patent medicines in the treatment of coronavirus disease 2019 (COVID-19) in China. Frontiers in Pharmacology 11:1066. https://doi.org/10.3389/fphar.2020.01066 FIELD OF THE INVENTION The instant invention relates to treatment of the novel coronavirus disease of 2019 (COVID-19). More specifically, this application discloses compositions of, and compounds found, in combinations of up to 14 Kenyan plants, including Dovyalis abyssinica and clutia robusta, which are effective in treating COVID-19 in humans. BACKGROUND OF THE INVENTION In this application, prior patents to the present inventors that are identically assigned to this application are referenced and sometimes cited at length, specifically: U.S. Patent Nos. 7,556,830; 7,674,483; 8,053,002; 8,067,401; 8,404,284 and 8,697,660; South African Patent No. 2011/09418; Kenya Patent No. 552; European Patent No. 1,919,490 B1; and Japan Patent 5,469,862. The disclosures of these documents in their entireties are hereby incorporated by reference into this application. But this application does NOT claim the effective priority date of the prior patents to the present inventors. The instant application is directed to a new medical use of the compositions and compounds that were disclosed in the aforementioned earlier patents, which were filed well before the existence of the COVID-19 disease became known. Various publications, published patent applications, and patents are also referenced, in order to more fully describe the state of the art to which this invention pertains. They, and the following discussion of the background of the invention, are merely provided to aid the reader in understanding the invention, and are not admitted to describe or constitute prior art to the invention. References provided with this application that are not discussed herein are considered to be cumulative of those that are. Additional references from the vast COVID-19 literature might have been multiplied in connection with the instant application, but Applicants have not done so. This is to avoid burdening and burying the examining Office(s) with references deemed to be non-pertinent and not material. See applicants’ discussion of the WHO’s COVID-19 Global Literature on Coronavirus Disease database, 7 paragraphs below. Hundreds of millions of people worldwide have been infected and affected by the novel Coronavirus Disease of 2019 (COVID-19) pandemic. Despite massive experimentation, at the time of this writing, “No therapy has been proven to be beneficial in outpatients with mild to moderate COVID-19 who are not at high risk for disease progression” (COVID-19 Treatment Guidelines Panel, May 21, 2021, p. 75). The utility of the instant invention is not limited to mild to moderate COVID-19 cases, but it is effective in the mild to moderate cases for which no therapy currently exists that is suitable for all patients. Remdesivir was approved or granted emergency authorization for use in 50 countries during part of 2020 (“Remdesivir,” 2021, para. 1), including in the U.S. in October by the FDA (United States Food and Drug Administration, October 22, 2020). Soon after, in November of 2020, the World Health Organization conditionally recommended against the use of remdesivir in the treatment of COVID-19 (World Health Organization 2020, November 20, p. 3). Despite the subsequently questioned efficacy of Remdesivir against COVID-19, a new U.S. Patent No. 10,695,361 B2 had already been issued to Gilead Pharma on June 30, 2020, for treating a Coronaviridae infection with this older medicine, which had been originally created in 2009 to treat hepatitis C and respiratory syncytial virus (“Remdesivir”, 2021, para. 21). Remdesivir, though still FDA-approved in the U.S., is currently recommended ONLY for hospitalized patients who require supplemental oxygen or high-flow oxygen delivery, but not “invasive mechanical ventilation or ECMO [Extra-Corporeal Mechanical Oxygenation]” (COVID-19 Treatment Guidelines Panel, op. cit., p. 75). Pfizer’s Paxlovid, if approved, may prove to be an oral therapeutic for mild-to-moderate COVID infection. It is currently being advertised as 89% effective in preventing hospitalization and death when administered within 3 days of the onset of symptoms in high-risk patients (Pfizer Press Release, December 14, 2021). This rather narrow band of utility may be a drawback, as patients with mild COVID may not be aware that their symptoms are something other than a cold, and therefore may not seek out testing and treatment in a timely manner. The cost of the medication is projected to be high, at $529 per course to the U.S. Government, which has contracted for millions of doses pending approval. The safety profile of the new medication PF-0732133 is not well known, while Ritonavir, previously used as an ARV, and which is also compounded in Paxlovid, has a multitude of side effects and drug interactions. A careful reading of the Pfizer press release indicates that the topline number of an 89% reduction in hospitalizations is not achieved in all studies. This is reminiscent of Merck’s Molnupiravir, which was at first touted as effecting a 50% reduction in hospitalizations, a number which was later lowered to 30% (Kozlov, M., 2021, December 13). Molnupiravir has also raised concerns in some quarters over its mutagenic mechanism of action (Cohen, J. & Piller C., 2020, May 13) and, at a minimum, is not recommended for pregnant women for those reasons. Various monoclonal antibodies have been proposed, studied, or granted emergency use authorization (in at least one case later suspended). They include casirivimab/imdevimab, bamlanivimab/etesevimab, and bamlanivimab. All of them are expensive, and must be administered intravenously in a hospital. Recent studies indicates that some of them may not be effective against the Omicron SARS-COV-2 variant (Burger, L., 2021, December 15, 2021). The development of COVID-19 vaccines does not eliminate the need for therapeutics. Unvaccinated populations exist and persist. SARS-CoV-2 variants continue to develop. An increasing number of breakthrough cases in vaccinated individuals has been reported. Existing vaccines in general, and the Chinese Sinovac and Sinopharm products in particular (Morrison, C., 2021 June 25), are more effective in preventing hospitalization and death than mild or moderate reinfection (W.H.O., 2021, June 22, pp. 5-6). The Omicron variant has significant escape from both vaccine- and infection-elicited immunity (Zhang et. al, 2021, December 10). Initial assessments that the Omicron variant is less virulent than earlier strains have been disputed by British scientists (Ferguson, et al., 2021, December 16). Future variants may be even more intractable. 89% of epidemiologists polled in a survey expressed the view that COVID-19 is very likely or likely to become endemic (Philips, N. (2021, February 18), even with vaccines in existence. In this scenario, and despite the efforts that have been made heretofore, the urgent need for COVID-19 therapeutics which is felt worldwide remains undiminished. More specifically, there is need for an oral therapeutic which can be administered at all stages of the COVID-19 disease, to all populations, outside a hospital setting, at low cost. Massive worldwide research and experimentation has been devoted to COVID-19 and the SARS-CoV-2 virus that causes it. Some of that research has been directed to evaluating the effectiveness of repurposed existing medications in treating COVID-19 (Kifle, et. al, 2021, April 22). In addition to remdesivir, without limitation, hydroxychloroquine, ribavirin, lopinavir, favipiravir, ritonavir, ivermectin, umifenovir and camostat mesylate are among the existing medications that have been studied in connection with their potential usefulness in treating COVID-19 (Verma et al., September 2020, p. 3). Medicines other than Applicants’ that were developed for HIV/AIDS have not been shown to work. “Although some ARV drugs are being studied for the prevention and treatment of COVID-19, no agents have been shown to be effective.” (COVID-19 Guidelines Panel, op. cit., p. 308). The literature also contains considerable discussion of the use of various herbal and/or traditional medicines in the treatment of COVID-19. A preponderance of such references discusses Chinese herbal medicines (TCM’s) such as Lianhua Qingwen. (Li, et. al., 2020, August 19). Beyond the borders of China, Lianhau Qingwen has been licensed as a prescription medicine by the Philippines F.D.A., but not for the treatment of COVID-19 (Philippines Food and Drug Administration 2021, April 30, and April 5). It is also approved in some other jurisdictions. It does not contain any of Applicants’ plant species. The use of a wide variety of TCM’s in connection with COVID-19 is discussed in Huang, et. al., 2020, October 16. None of Applicants’ plant species is disclosed, and there is no overlap of Applicants’ isolated compounds with the “lead compounds with greatest drug-likeness for COVID-19” in Huang (p. 13). Similarly, Luo et. al (2020, September 11) reports on 78 TCM plants, some of which reappear in different formulated combinations, which are thought to have potential usefulness in connection with COVID-19. None of the plants coincide with Applicants’. Other traditional pharmacopoeias are also referenced. Indian medicinal plants are discussed in Ahmad, et al. 2021, March 2. None of Applicants’ plants are mentioned. In Pakistan, Kousar et al. (2020, October 13) performed an in silico analysis of the potential activity against SARS-CoV-2 of 2035 phytochemicals isolated from hundreds of plant species. None of said species were those of Applicants. Attah et. al. in Nigeria (2021, April 26) reviewed the therapeutic potentials against COVID-19 of plants used in traditional African medicine, and did not mention any of those used in the instant invention. In fact, a search of the 439,413 publications indexed on the WHO’s COVID-19 Global Literature on Coronavirus Disease database, performed on December 19, 2021, fails to uncover A SINGLE REFERENCE that mentions either “Dovyalis” or “Clutia”, in its title, abstract or subject, let alone “Dovyalis abyssinca” and “Clutia robusta”. The combination of these last- mentioned plant species, or of chemical compounds which may be found therein, form the basis of Applicants’ independent claims. The inescapable conclusion is that the COVID-19 therapeutics disclosed in the instant patent application have not been anticipated anywhere. Ancient societies have traditionally turned to plants for their health needs. Documented use of herbs to treat diseases dates back to as early as 2,000 B.C. It is well-known in the art that any given plant may contain a plurality of pharmacologically active chemical compounds, and that these compounds may function synergistically to create a therapeutic effect (Prasad et. al. 2020, June 19). The potential synergies can be exponentially increased when combination therapy with a plurality of plants is deployed (Spjut, R., 2005, p. 2223), as in the instant application. It is well-known to those skilled in the art that citation of a plant as medicinal somewhere in ethnomedical literature is not proof of its effectiveness for the indicated condition, let alone for something else. Spjut (p. 2221), identified 2,127 allegedly “active” plant species as “leads” for treating cancer, and yet cancer is still with us. Laundry lists of species, of which Spjut’s is an extreme example, are common in the art. Such lists offer no practical direction or guidance that those skilled in the art can use to make an effective medicine, absent undue experimentation, and bare recitation of a plant in botanical literature (as in Bally, P.R.O., 1946, December 1), is not indicative of its usefulness for any medicinal purpose. Scattered references to some, but not all, of Applicants’ herbs appear from time to time in lists of reportedly useful medicinal plants for other conditions, such as Spjut’s supplemental material (U.S. Department of Agriculture Agricultural Research Service, 1980). This reference is even more voluminous than Spjut’s 2005 article, and it mixes inexact entries for entire genera with those for individual species. Some of Applicants’ plants are mentioned, and others are not, while an enormous mass of vegetation extraneous to the instant invention is also included. A dragnet approach to the material which is hit-or-miss with respect to Applicants’ plants also characterizes other, more recent plant lists in the non-COVID herbal medicine literature. This true even when the lists are less long than those given in Spjut and his sources, and are focused on plants indigenous to the same geographical region as those disclosed in the instant invention. See, e.g., Omara, T., 2020, June 12, describing Kenyan plants used as antimalarials; and Nankaya, et. al., 2019, December 27, listing plants used by the Maasai as remedies for various conditions. The medicinal species lists given in the art are simply NOT CONGRUENT with the plants used by Applicants. Applicants’ herbal compositions could only be PARTIALLY reconstructed from a multiplicity of references, even with the benefit of hindsight. No matter how they are combined, the prior art references do not contain an enabling disclosure that would teach, suggest, or motivate one skilled in the art to use or combine the plants to treat COVID-19. Further, the full constellation of isolated compounds disclosed by applicants, and their hypothesized synergistic therapeutic effects, have not been explored anywhere. The only known third- party study of Applicants’ compositions and compounds was performed under Applicants’ control and supervision, and was an in vitro and in silico investigation which explored the question of why some of the compounds in Applicants’ plants might be active against HIV 1(Rotich et al., 2021, September 30). The results of that study, which were not conclusive, are in any event not pertinent to the use of the selected subset of compounds to treat COVID-19. “Despite the volume of research on computational screening analyses from different databases, there is a paucity of information on small molecules from African medicinal plants that can help combat SARS-CoV-2” (Iheagwam & Rotimi, 2020, September 14). By contrast, Applicants’ compositions and compounds have previously been disclosed and experimentally validated in the treatment of HIV/AIDS in humans, producing sero-reversion in some cases. Unpredictably, those same compositions and compounds are also useful in the treatment of COVID-19. Many proposed repurposed therapies for COVID-19 have failed. The example of hydroxychloroquine is well known (W.H.O. 2021, May 21). Applicants’ unexpected success where others have failed is evidence of invention, and should not be taken as an inherent sign of lack of credibility. SUMMARY OF THE INVENTION The present invention is based upon the discovery of the unique antiviral properties of a herbal remedy composition prepared from a variety of plants native to Kenya. The herbal composition of the present invention can include plant material from between two and 14 different plants including Dovyalis abyssinica (representative seed of said line having been deposited under ATCC Accession No. PTA-6969) and Clutia robusta (representative seed of said line having been deposited under ATCC Accession No. PTA-6970). In other embodiments of the invention, the herbal pharmaceutical composition may also include plant material from one or more of the following: Prunus africana, Croton macrostachyus, Acacia nilotica (representative seed of said line having been deposited under ATCC Accession No. 7378), Rhamnus prinoides, Adenia gummifera, Asparagus africanus, Anthocleista grandiflora, Plantago palmata (representative seed of said line having been deposited under ATCC Accession No. PTA-7377), Clematis hirsuta, Ekebergia capensis, Bersama abyssinica, and Periploca linearifolia. In one aspect, the invention provides a herbal composition for treating infectious diseases, such as for example, COVID-19. The composition containing plant material includes the roots of Dovyalis abyssinica and the roots of Clutia robusta. In other embodiments of the invention, the herbal pharmaceutical composition may also include plant material, as indicated, from one or more of the following: stem bark of Prunus africana, stem bark of Croton macrostachyus, stem bark of Acacia nilotica, roots of Rhamnus prinoides, roots of Adenia gummifera, roots of Asparagus africanus, stem bark of Anthocleista grandiflora, whole plant of Plantago palmata, roots of Clematis hirsuta, stem bark of Ekebergia capensis, stem bark of Bersama abyssinica, and roots of Periploca linearifolia. In another aspect, the invention provides illustrative methods for preparing a liquid extract of the solid herbal composition of the invention. The extraction of plant material can be done with hot water. The aqueous extract can be used for treating COVID-19. In one embodiment, hot aqueous extraction is done under basic conditions, followed by hot aqueous extraction under acidic conditions. In another aspect of the invention, extracts of the herbal compositions can be processed to produce a concentrate in semi- solid or solid form, ground when dry to create a powder, and further processed to make a pharmaceutical composition. If required, herbal extracts and/or concentrates can be processed, washed and/or cleaned to remove toxic residues or compounds. In another aspect, the subject invention provides illustrative processes for preparing the composition disclosed herein comprising isolating compounds from one or more plant sources. It is known in the art that “…. phytotherapeutics with multiple therapeutic uses likely contain several different active constituents or contain compounds with work synergistically to produce the desired therapeutic effects” (Ruiz et. al, 2016, July 26). Compounds isolated by applicants which are thought to be candidates in the production of the synergistic therapeutic effect are presented in Tables 1, 2 and 3, in the Detailed Description of the Invention below. The subject invention further provides preparing the pharmaceutical compositions disclosed herein comprising one or more synthesized isolated compounds and/or ingredients. The herbal compositions and pharmaceutical compounds may be administered at least once a day. In other embodiments, the compositions and compounds are administered twice or three times daily, based upon the condition of the subject. In other embodiments, the compositions and compounds may be administered as a beverage, capsule, tablet, powder, syrup, candy, gel, nutritional product, or pharmaceutical product. The compositions and compounds may be further mixed with excipients as is known to those of skill in the art, many of which are listed in Chapter 36 of “Remington Essentials of Pharmaceutics” (Felton, L. (Ed.) 2013, pp. 683-704). In a preferred embodiment, but without limitation, a pharmaceutical composition prepared from extracts of the plants has demonstrated effectiveness in treating COVID-19-positive subjects, as subjects treated with it have experienced non- progression of the disease, and quick disappearance of any symptoms. This invention will be better understood by reference to the Experimental Details which follow, but those skilled in the art will readily appreciate that the specific experiments detailed are only illustrative of the invention as described more fully in the claims which follow thereafter. BRIEF DESCRIPTION OF THE DRAWING FIG. 1 shows “classification of COVID-19 disease states and potential therapeutic targets. The figure illustrates 3 escalating phases of COVID-19 disease progression, with associated signs, symptoms, and potential phase-specific therapies” (Siddiqi & Mehra, 2020, March 20). DETAILED DESCRIPTION OF THE INVENTION Definitions "About", as used herein, means in quantitative terms plus or minus 10%. “Amelioration”, as used herein, of the symptoms of a particular disorder by administration of a particular composition refers to any lessening, whether permanent or temporary, lasting or transient that can be attributed to or associated with administration of the composition. “Antigen test” (in relation to COVID-19), as used herein, detects antibodies to SARS-CoV-2 in a subject. “Antiviral” as used herein, refers to a substance or process that destroys a virus or suppresses replication (reproduction) of the virus. “ARV” means "antiretroviral", as used herein, refers to a substance or process that destroys a retrovirus or suppresses replication (reproduction) of the retrovirus, including HIV. “CD4+ T cell” (or “CD4”), as used herein, refers to an immune T cell which is involved in protecting against infectious agents including viral, fungal, and protozoal infectious agents. The CD4 molecule is expressed on the surface of T helper cells, and serves as the primary target for HIV-1 and HIV-2. CD4 is the co-receptor for the T cell receptor and recruits the tyrosine kinase 1 ck intracellularly. CD4 cell counts are reduced with the progression of HIV. "Combination", as used herein, refers to any association between or among two or more items. The combination can be two or more separate items, such as two compositions or two collections. It can be a mixture thereof, such as a single mixture of the two or more items, or any variation thereof. "Composition", as used herein, refers to any mixture. It can be, without limitation, a solution, a suspension, liquid, powder, a paste, aqueous, non-aqueous or any combination thereof; and may be presented, without limitation, as a beverage, capsule, tablet, powder, candy, gel, nutritional product, or pharmaceutical product. “COVID-19”, as used herein, refers to any infection, illness or syndrome, caused directly or indirectly by SARS-CoV-2, including asymptomatic infections. “Extract”, as used herein, refers to a solution containing compound(s), usually in a concentrated form, obtained by treating a solid material (such as for example, plant material) with a solvent to remove desired compounds or components. "Extraction", as used herein, refers to a method of separation in which a solid or solution is contacted with a liquid solvent to transfer one or more components of the solid into the solvent. “Highly active antiretroviral therapy”, or HAART, as used herein, refers to treatment regimens designed to aggressively suppress viral replication and progress of HIV disease, usually consisting of three or more different drugs, such as for example, two nucleoside reverse transcriptase inhibitors and a protease inhibitor. “Ingredient”, as used herein, refers to one or more materials used in the manufacture of a composition. Ingredient can refer to a pharmaceutically active ingredient or to other materials in the composition. Ingredients can include, without limitation water, other solvents including non-aqueous solvents, salts, buffers, surfactants, excipients, and flavorings. "PCR test" (in relation to COVID-19), as used herein, refers to a test that measures the presence of genetic material from SARS- COV-2 in a subject. "Pharmaceutical composition", as used herein, refers to a composition that contains at least one pharmaceutically active ingredient, and one or more other pharmaceutically-acceptable ingredients, that is formulated for administration to a human subject. "Pharmaceutically-acceptable", as used herein, indicates that the identified material does not have properties that would cause a reasonably prudent medical practitioner to avoid administration of the material to a subject, taking into consideration the disease or conditions to be treated and the respective route of administration. "SARS-CoV-2”, as used herein, means the virus that causes the Novel Coronavirus Disease of 2019 (COVID-19), inclusive of all of its variants. “Synergy” or “synergistic effect”, as used herein, refers to an ameliorative therapeutic effect of a treatment with a combination of active ingredients that is greater than the ameliorative result which results from using the agents separately. "Synthesized alkaloid compounds", as used herein, refers to alkaloid compounds obtained by chemical synthesis. "Synthesized steroid glycoside compounds", as used herein, refers to steroid glycoside compounds obtained by chemical synthesis. "Synthesized terpenoid compounds", as used herein, refers to terpenoid compounds obtained by chemical synthesis. "Therapeutically effective" or "effective amount", as used herein, indicates that the materials or amount of material is effective to prevent, alleviate, or ameliorate one or more symptoms of a disease or medical condition, and/or to prolong the survival of the subject being treated. “Treatment”, as used herein, refers any manner in which the symptoms of a condition, disorder or disease or other indication, are ameliorated or otherwise beneficially altered. “Viral load test” (in relation to HIV), as used herein, refers to a test that measures the quantity of HIV RNA in the blood, expressed as number of copies per mL of blood plasma. Discussion The present invention relates to the discovery that combinations of plants native to Kenya can be used in the treatment of COVID- 19. Herbal compositions prepared from combinations of the extracts of the following: the roots of Dovyalis abyssinica and Clutia robusta, the roots of Rhamnus prinoides, Adenia gummifera, Asparagus africanus, Clematis hirsuta, and Periploca linearifolia, the stem bark of Ekebergia capensis, Bersama abyssinica, Prunus africana, Croton macrostachyus, Acacia nilotica, and Anthocleista grandiflora, and the whole plant of Plantago palmata have been shown to be particularly effective in improving the health of infected subjects. Specifically, herbal compositions of the present invention are particularly well suited for the treatment of COVID-19. Compositions of the invention can be prepared from plant material collected from the Mau Forest Complex in Western Kenya. Herbal compositions prepared from aqueous extractions and purified extracts of plants from this region of Kenya exhibit increased potency in the treatment of infectious diseases. The Mau Forest Complex is located at 0 degrees, 30' South, 35 degrees, 20' East and in the Rift Valley Province, and spans four Kenyan administrative districts: Narok, Nakuru, Bomet and Kericho. Mean annual rainfall varies from 1000 to 1500 mm with peaks in April and August. The rainfall pattern at the eastern flanks is governed by the moist monsoon winds from the Indian Ocean and dry winds from the Great Rift Valley. The western flanks of the Mau Forest Complex are influenced by the Lake Victoria macroclimatic region, and are generally wetter, with annual rainfall greater than 2000 mm, and it is more evenly distributed. Mean annual temperatures for the Mau Forest Complex range from 12-16 degrees C. The soil of the Mau Forest Complex is rich volcanic loam having a pH between 3.8-5.8. The vegetational pattern follows an altitudinal gradient with local topographical ecolines. The closed canopy moist mountain forest at lower altitudes becomes increasingly intermixed with bamboo from 2200 m onwards. Between 2300 and 2500 m, pure bamboo (Arundinaria alpina) swards are found. Above 2500 m this gives way to mixed bamboo/tree stands, both associated with grass clearings that usually represent a sub-climax resulting from burning and cutting of bamboo. A marginal type of mountain sclerophyll forest, wherein the plants generally have hard leaves to prevent wilting during dry conditions, occupies the highest altitudes of the Mau complex. Plants in the Western flank of the Mau Forest Complex have shown the highest potency for the herbal compositions. Plants growing in the Western flank, (which is generally a high rainfall, high altitude region), have fewer environmental stresses. It is therefore possible that plants of the Western flank have more biosynthetic pathways, which may in turn lead to the production of a greater number of diverse compounds, which may in turn explain the greater potency of plants from the Western flank (as compared to other regions of the Mau Forest Complex). Alternatively, the greater potency plant extracts from the Western flank plants may be a result of a greater variety and number of alkaloids and other compounds in the plant extracts, such that the combined effect is greater than the sum of their individual effects. The East Mau Forest Complex has a drier vegetation of cedar and podo. Wherever these species have been identified, colonizing species such as Neuboutonia marcrocalyx and Macaranga capensis can be found. The compositions of the invention may be prepared using plants collected from three altitude ranges of the Mau Forest Complex: 2000 m above sea level (annual rainfall of 1000 mm), 2300 m above sea level (annual rainfall 1500 mm), and 2500 m above sea level (the Western Mau flank, annual rainfall greater than 2000 mm). The Western flanks of the Mau Forest contain plants that are particularly preferred for preparing the herbal compositions of the invention. The plants grown in the drier Eastern flank of the Mau Forest Complex also may be used. Plant material for preparing compositions of the invention may also be obtained from plants grown in a greenhouse environment. The germination of the seeds of particular plants may be altitude or soil dependent. Seeds for greenhouse planting may require collection from the natural dispersal agents as they exist in the wild. Additionally, simulation of rainfall, sunlight (an average of 12 hours per day in the Mau Forest Complex), and soil conditions of the Mau Forest Complex (i.e., rich volcanic loam having a pH between 3.8-5.8) may be required to obtain plants of similar potency. The seeds of Dovyalis abyssinica (representative seed of said line having been deposited under ATCC Accession No. PTA-6969) are contained in a fleshy fruit. There are about 4 seeds enclosed by the flesh. A ripe fleshy fruit can be soaked in water for about 4 days, to make it possible to squeeze with minimum force to release the small seeds, each being approximately the size of a tomato seed or slightly larger. The seeds are then washed, dried and stored, awaiting germination under Mau Forest-like environmental conditions. In the wild, the fruit flesh is soaked by rainwater, which results in the release of the seeds. The seeds grow naturally under the environmental conditions of the Mau Forest Complex as described above. The Clutia robusta (representative seed of said line having been deposited under ATCC Accession No. PTA-6970) seeds are much smaller and encased in berries having a nut-like outer covering which encases approximately 3 to 4 seeds the size of a grain of sand. When mature seeds are exposed direct sunlight, they disperse rapidly in a process called explosive dispersal. This is not a problem in the wild, but if one is interested in collecting the seeds, care and intelligence are required, or else all the seeds will fly away under the scattering effect of the hot sun. To recover the clutia robusta seeds, the berries should be placed in a metallic container, and covered with a material that allows sunlight to enter, such as a transparent polyethylene film surrounding a container of appropriate wire mesh. Exposure to light will cause the shells to break open, releasing the seeds which can then be separated from the chaff. The optimal time for planting the Clutia robusta and Dovyallis abyssinca seeds in their natural environment is during the long rains, typically around the month of April. However, in the wild, the plants will generally grow throughout the year, except during the dry season, as the plants require a considerable amount of water and light to grow. Croton macrostachyus produces pale pea-sized capsules, on drooping spikes to 30 cm long, splitting open on the tree to release 3 shiny grey seeds, covered at one end by a soft, creamy aril, or envelope. Prunus Africans produces spherical fruit, about 10 mm in diameter which is pinkish brown in color. The Acacia nilotica (representative seed of said line having been deposited under ATCC Accession No. PTA-7378) plant produces straight or curved pods measuring approximately 17 by 2 cm. When young, the pods are green and fleshy, but they get darker with age, and are usually velvety. Pods have a fruity odor and open on the ground to release seeds. Ekebergia capensis produces rounded, thin skinned berries, up to 2.5 cm in diameter, on long stalks in heavy bunches, which are yellow to red in color when mature. The berry-like fruits of Rhamnus prinoides are approximately the size of a pea (about 5 mm in diameter), roundish and clearly divided into three compartments. They are fleshy and green, turning red and then purple as they ripen. The fruit of the Asparagus africanus is a round berry, approximately 0.5 cm in diameter, green aging to orange, found most of the year. It is spread mainly by birds carrying the seeds. The Anthocleista grandiflora produces fruits that are oval in shape, measuring approximately 3 cm. by .2 cm, glossy, smooth and brown when mature. Multi-seeded, large fruits are found throughout the year. The Bersama abyssinica produces a smooth, spherical capsule, measuring approximately 2.5 cm in diameter, golden velvety at first, losing most of the hair and becoming brown by maturity; splitting into four valves to reveal attractive bright red seeds, about 10 mm long, enveloped for about half of their length by a yellow, cup-shaped aril. Adenia gummifera produces a fruit which is a stalked 3-valved capsule, leathery or fleshy, often red; seeds are compressed with bony testa in a fleshy aril. Plantago palmata (representative seed of said line having been deposited under ATCC Accession No. PTA-7377) produces a capsule- like fruit with two seeds per capsule. Periploca linearifolia (representative seed of said line having been deposited under ATCC Accession No. PTA-7375) produces black seeds measuring approximately 10 mm long and 2 mm wide with white wool measuring around 3 cm attached to the tips of the seeds. The seeds are enclosed in pods measuring about 12 cm long. Upon maturity, the pods break open upon exposure to sunlight. This releases the seeds, which are borne aloft by the wool as they are dispersed by wind. Alternatively, these plants may be cultivated from stem cuttings, which when laid on or planted in the ground, grow roots, and propagate new plants. Clematis hirsuta (representative seed of said line having been deposited under ATCC Accession No. PTA-7383) produces yellowish seeds measuring approximately 3 mm in length and 1 mm in breadth. The seeds are surrounded by yellowish-white wool which measures about 5 mm long. The wool carries the seeds upon the wind, which is the dispersal agent. Based on our finding that certain combinations of certain plant material are effective treatments for COVID-19, certain compounds thought to be active have been isolated from each plant. The following plant material was used: dried root of Dovyalis abyssinica, dried root of Clutia robusta, dried stem bark of Prunus Africana, dried stem bark of Croton macrostachyus, dried stem bark of Acacia nilotica, dried root of Rhamnus prinoides, dried root of Adenia gummifera, dried root of Asparagus africanus, dried stem bark of Anthocleista grandiflora, dried whole plant of Plantago palmata, dried root of Clematis hirsuta, dried stem bark of Ekebergia capensis, dried stem bark of Bersama abyssinica, and dried root of Periploca linearifolia. The preferred weight ratio of the aforementioned plant material is 2:2:2:2:2:2:1:2:2:1:2:2:2:2, respectively, and each was chopped into small parts, dried and mixed into a herbal mixture. Other weight ratios can also be used. The alkaloids specified in Table 1 were isolated from the plant material by first grinding each individual herb. Then, base was added to obtain a basic solution and said mixture was heated. Sufficient base is added to the defatted herbal material to achieve a pH of approximately 8. The concentration of the base added can be adjusted to provide sufficient liquid volume to cover the defatted herbal solid mixture. Any suitable base may be used, with preferred bases including NaOH, KOH, Ca(OH)2, Mg(OH)2, NH4OH, and the like. The base extract is then heated for 2-4 hours. Preferably, the ingredients are slowly simmered under reflux conditions, although the same effect can be achieved by simmering the mixture in a covered pot. Subsequently, acid was added to obtain an acidic solution, and said solution was heated. The acid was aqueous HCl and the pH of the acidic solution was about 3. Preferably the acid is HCl, although other acids, including but not limited to, HBr, HNO3, H2SO4, H3PO4, or any other acid suitable for achieving a pH of approximately 3 may be used as well. The concentration of the acid can be adjusted as necessary to provide sufficient volume to the mixture. The acidified solution is then boiled for approximately 2-4 hours under the same conditions employed for the heating of the basic solution. After heating, the mixture is cooled, and the aqueous layer is separated from the mixture, such as for example, by decanting the liquid from the remaining solids. Acid is then added to the remaining residue sufficient to achieve a pH of approximately 3, and the mixture is then reheated for approximately 2-4 hours under the same conditions previously employed. The aqueous layer is separated from the ingredients and the two acidified layers are combined. If necessary, additional acid extractions may be performed. Then, the acidic solution was decanted to provide an acidic extract and a residue, acid was added to the residue and the acid and residue were heated at a simmer for about four hours. The acid was aqueous HCl. However, other extractive treatments, by heat or otherwise, could be used, and are within the scope of this invention. For example, ethanol can be used as a solvent in some extractive processes. Alkaloids were extracted from said acidic solution with a non- polar solvent, e.g. ether. Non-polar solvents are generally organic solvents having a dielectric constant less than 20. Non-polar solvents that may be used include, but are not limited to: alkanes, 1,4-dioxane, carbon tetrachloride, chloroform, methylene chloride, benzene, ethers, ethyl acetate, tetrahydrofuran, acetic acid, butanol, chlorobenzene, cycloalkanes, xylene, and the like. Preferred non-polar solvents are xylene and ether. The non-polar solvent added was about 20% by volume. However, other volume percentages could be used, and are within the scope of this invention. The alkaloids were precipitated and collected at a pH of about 9 to isolate the alkaloids. However, other precipitative treatments, and/or other PH levels, could be used, and are within the scope of this invention. Likewise, other methods of extraction known to those of skill in the art, or which may come to be known by them, could be used, and are within the scope of this invention. The precipitated alkaloid mixtures from each of the 14 plants were subjected to repeated column chromatography. Silica gel was used as a stationary phase. However, other stationary phases could be used, and are within the scope of this invention. The column was first eluted with n-hexane, followed by varying proportions of ethyl acetate, until 100% ethyl acetate was added. The column was finally washed with methanol. Other elutants than n-hexane could be used, and could be followed by other compounds than ethyl acetate until different proportions were reached. The column was finally washed with methanol, although other washing agents could be used. The foregoing variations are within the scope of this invention. Structures of each of the isolated alkaloids were elucidated using a combination of spectroscopic and physical data. Other methods of elucidation which are available now or which may come to be available in the future could be used, and are within the scope of this invention. The isolated alkaloids are useful in the treatment of COVID-19. As shown by Table 8 set forth herein, extracts of the mentioned plants are an effective treatment of COVID-19 in subjects in need of such treatment. The alkaloid compounds in a plant are thought to be among the active compounds in the plant. That is, the alkaloid compounds isolated from each plant set forth in Table 1 have at least analogous activity to the extracts. Further, terpenoids are known to be pharmacologically active in some cases. When terpenes are modified chemically, such as by oxidation or rearrangement of the carbon skeleton, the resulting compounds are generally referred to as terpenoids. Some authors will use the term terpene to include all terpenoids. Terpenoids are also known as isoprenoids. Terpenoid compounds were serially extracted from the relevant chopped and ground parts of each plant. A conventional Soxhlet extraction process was used, with n-hexane as the solvent, though other means of extraction, will occur to those skilled in the art can be used as well. The extracts were then subjected to nuclear magnetic resonance (NMR) and mass spectroscopy (MS). Chemical structures of the terpenoids were elucidated by comparing and corroborating the obtained spectroscopic data with standard compounds in the Merck Index Library. Other methods of elucidation which are available now or which may come to be available in the future could be used, and are within the scope of this invention. The terpenoids isolated and elucidated by applicants have been set forth in Table 2. They are thought to comprise a portion of the synergistic effect of the invention. Further, steroid glycosides are known to be pharmacologically active in some cases. A method of isolating steroid glycosides is as follows. Chopped plant materials were coarsely powdered and extracted in a Soxhlet apparatus with chloroform for 12 hours. The chloroform extract can be concentrated to obtain a dark viscous mass. A small amount of the extract was screened chemically for determination of different phytoconstituents. The concentrated extract was dissolved in small quantity of chloroform and adsorbed on silica gel (60-120 mesh) for preparation of slurry. The slurry was then air-dried and chromatographed over a silica gel column. The column was eluted with chloroform-ethyl acetate (8:2, v/v). The chromatograms were then developed in an iodine chamber. The fractions were collected separately and matched by thin layer chromatography (TLC) to check their homogeneity. The fractions with the same retention factor (Rf) value were combined together and crystallized. The compound was then recrystallized with methanol and finally purified by preparative thin layer chromatography (TLC). The isolated compound was subjected to spectral and chemical studies for characterization. Other methods of extraction and elucidation which are available now or which may come to be available in the future could be used, and are within the scope of this invention. The steroid glycosides isolated and elucidated by applicants have been set forth in Table 3. They are thought to comprise a portion of the synergistic effect of the invention. Other methods of extraction and elucidation which are available now or which may come to be available in the future could be used, and are within the scope of this invention. Ethanol can be used in some extractive processes, alone, or in combination with water in hydroethanolic extraction. Many other methods of extraction and elucidation are known in the art. One or more of the isolated compounds set forth in tables 1, 2 and 3 below may be synthesized according to methods which are known or will occur to those skilled in the art, and may be therapeutically administered, or comprised in any composition or pharmaceutical composition of the invention.
Table 1: Specific Alkaloids present in each plant
Figure imgf000041_0001
Figure imgf000042_0001
Figure imgf000043_0001
Figure imgf000044_0001
Figure imgf000045_0001
Figure imgf000046_0001
Figure imgf000047_0001
Figure imgf000048_0001
Table 2: Specific Terpenoid(s) present in each plant
Figure imgf000049_0001
Figure imgf000050_0001
Figure imgf000051_0001
Figure imgf000052_0001
Figure imgf000053_0001
Table 3: Specific steroid glycoside (s) present in each plant
Figure imgf000054_0001
Figure imgf000055_0001
Figure imgf000056_0001
Figure imgf000057_0001
Figure imgf000058_0001
Pl t St t
Figure imgf000059_0001
l
Figure imgf000060_0001
l
Figure imgf000061_0001
l
Figure imgf000062_0001
l
Figure imgf000063_0001
l
Figure imgf000064_0001
Figure imgf000065_0001
Figure imgf000066_0001
Figure imgf000067_0001
Pl t St t
Figure imgf000068_0001
Pl t St t
Figure imgf000069_0001
OH
l
Figure imgf000070_0001
Pl t St t
Figure imgf000071_0001
l
Figure imgf000072_0001
Figure imgf000073_0001
Experimental details This invention will be better understood by reference to the Experimental Details which follow, but those skilled in the art will readily appreciate that the specific experiments detailed are only illustrative of the invention as described more fully in the claims which follow thereafter. Determination of bioactivity of compositions having the disclosed compounds The efficacy of compositions having the disclosed compounds were tested against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The specific compositions were in the form of plant extracts. Solutions containing 100 ppm (parts per million) of each plant extract were prepared for use in the anti-bacterial assay. Preparation of bacterial culture of E. coli and S. aureus Standard cultures of E. coli (representing gram-negative strains of bacteria) and S. aureus (representing gram-positive bacteria) were obtained from Moi University Teaching and Referral Hospital. Assays were conducted at the Moi University Department of Botany in Eldoret, Kenya. Nutrient agar was used as growth medium for both bacteria samples. The agar was sterilized in an autoclave at 120°C, cooled and poured into sterile Petri dishes and allowed to set. Sterile conditions were achieved and maintained by exposing the area to a UV lamp during sample preparation and the assay procedure. The cooled agar medium was streaked on the surface with each bacteria culture. Wells were dug in the middle of the medium, using a cork borer, where the prepared plant extract was deposited. A control experiment was also performed, using plain sterile water in place of the plant extracts. Cultures were incubated for 12 hours, after which zones of inhibition of bacterial growth were determined and measured. Bacteria-growth inhibition was expressed in diameters (mm), and was determined by measuring the distance from edge of the well to area where the bacteria begin to show growth. Generally, the larger inhibition diameter indicates greater potency of the particular extract against the bacteria. Of the 23 plants which were screened in this assay, 14 of the plants had bacteria growth inhibition diameters greater than 8 mm, which was previously determined to be the minimum activity required for adoption of the extract for the herbal remedy. The anti-bacterial activities of the plants were compared with standard antibiotics. Of the 14 plants having inhibition diameters greater than 8 mm, Dovyalis abyssinica and Clutia robusta demonstrated the greatest anti-bacterial activity. Results for plant extracts exhibiting inhibition diameters greater than 8 mm are provided in Table 4.
Table 4: Inhibition Diameters
Figure imgf000076_0001
HIV/AIDS therapy with the instant invention Preparation of the compositions of the invention for treating HIV/AIDS The compositions and compounds that were used in the Examples below were prepared and isolated from the roots of Dovyalis abyssinica and Clutia robusta, and optionally one or more of the following: the stem bark of Prunus africana, stem bark of Croton macrostachyus, stem bark of Acacia nilotica, roots of Rhamnus prinoides, roots of Adenia gummifera, roots of Asparagus africanus, stem bark of Anthocleista grandiflora, whole plant of Plantago palmata, roots of Clematis hirsuta, stem bark of Ekebergia capensis, stem bark of Bersama abyssinica, and roots of Periploca linearifolia. Preferably, the ingredients collected are fresh, although dried samples may also be used. The ingredients are combined and chopped into small pieces and dried. The compounds can be used in the following weight ratio, by reference to the plant from which they are isolated: Dovyalis abyssinica, Clutia robusta, Prunus africana, Croton macrostachyus, Acacia nilotica, Rhamnus prunioides, Adenia gummifera, Asparagus africanus, Anthocleista grandiflora, Plantago palmata, Clematis hirsuta, Ekebergia capensis, Bersama abyssinica and Periploca linearifolia, in a weight ratio of 2:2:2:2:2:2:1:2:2:1:2:2:2:2, respectively. Administration of the Composition The plant extract precipitates are preferably purified and collected in either crystalline, paste or powder form. The precipitates can be administered to a subject as a beverage, capsule, tablet, powder, candy, gel, nutritional product, pharmaceutical product, or other form. The amounts for administration may vary and may be readily determined by those of skill in the art. For example, the amount may be from 0 to about 50 grams, from about 0.5 grams to about 35 grams, from about 0.1 and 25 grams, from about 0.1 to about 10 grams, or from about 0.1 grams to about 5 grams of alkaloids, distributed in whatever composition form, are administered per day to an infected subject. In one non-limiting example, the herbal composition is administered as a beverage wherein approximately 1 tbsp of powdered extract is dissolved in approximately 250 mL of hot water, and drunk. Other amounts and volumes will be recognized by those of skill in the art. Dosing is either twice daily at 12-hour intervals, or three times daily at eight-hour intervals (depending on the level of infection of the test subject), and is preferably administered with a meal. Other dose regimens are also possible. Subjects and experimental design Subjects in the Examples below were screened at the Walter Reed Hospital of the U.S. Army in Kericho, the Moi University Hospital in Eldoret, and at various Voluntary Counseling and Testing (VCT) Centers scattered throughout the country of Kenya. Subjects’ CD4 and CD8 counts were measured using a FACSCount™ system following procedures provided in the FACSCount White Paper (July 1994). HIV-1 and HIV-2 antibodies were detected using a bioMerieux Vironostika® HIV Uni-Form II Ag/Ab ELISA system. All subjects administered the herbal composition were HIV- positive adults. Prior to administration of the herbal composition, an initial CD4 count for each subject was determined, followed by an assessment of the level of opportunistic infections. Those with fewer opportunistic infections were administered the herbal composition twice daily after meals, at 12-hour intervals. Those with more opportunistic infections were administered the herbal composition three times daily, at 8 hours intervals. Each subject was given one week's dosage during each visit to the clinic. This was done to make it possible to monitor compliance, and to avoid the possibility of subjects sharing the drug with others. Example 1 Initial studies for the treatment of HIV positive subjects with the herbal remedy were conducted by treating four HIV-positive subjects with two different herbal remedies. Two subjects were administered a herbal composition which included the extract of Dovyalis abyssinica, while the other two subjects were administered a herbal remedy which included the extract of Clutia robusta. The subjects were each treated for a period of three months. The CD4 counts of both sets of subjects (i.e., those administered either Dovyalis abyssinica or Clutia robusta) increased by approximately 10 per month of treatment. Example 2 In another study, three subjects were administered a herbal composition prepared with a 1:1 ratio by weight mixture of Dovyalis abyssinica and Clutia robusta, for a period of approximately three months. The CD4 counts of the subjects treated with the mixture increased by approximately 30 per month, demonstrating a synergistic effect of the combination. The CD4 counts of the subjects treated with the combination increased by an amount greater than the sum of the increases in the CD4 counts of the patients treated with the individual ingredients. Example 3 In yet another experiment, 20 subjects were administered a herbal composition containing extracts of Dovyalis abyssinica, Clutia robusta, Prunus Africana, Croton macrostachyus, Acacia nilotica, Ekebergia capensis, Clematis hirsuta and Adenia gummifera. The 8 plant extracts were selected from the aforesaid 23 total plant extracts which had been previously assayed against E. coli and S. aureus. As shown in Table 5, CD4 counts of subjects increased by up to 100 per month, but none of the subjects tested HIV negative within the three-month period. An enhanced synergistic effect was demonstrated by the 8-herb combination. Table 5: CD4 Counts per Month
Figure imgf000080_0001
Example 4 In another experiment, 26 HIV-positive subjects were treated with a herbal composition consisting of the 14 herbal ingredients identified in Table 4. Subjects were administered a composition prepared by dissolving approximately 1 tbsp. (or 15 ml.) of the powdered ingredients (a mixture prepared with the 14 plants listed in Table 4) in approximately 8 ozs. (250 ml) of hot water. The supernatant liquid was then ingested by the subject. The subjects were divided into two groups: the first group having 10 subjects (subject ID Nos. 1-10) and the second group having 16 subjects (Subject ID Nos. 11-26). In the first group, each of the 14 plants was present in the composition in equal weight ratios. In the second group, the concentrations of Dovyalis abyssinica and Clutia robusta were approximately half of the other 12 ingredients as disclosed. As shown in Table 6, CD4 counts for each subject were measured on a monthly basis. The CD4 counts of the test subjects treated with the 14-ingredient herbal composition increased by up to 100 per month. Six subjects tested HIV-negative after four months of treatment. Two subjects tested HIV-negative after two months of treatment. The 14-herb combination therapy displayed a level of ameliorative synergy that has never been demonstrated in any HAART combination therapy, in that some of the subjects in sero- reversed and became HIV-negative. The difficulty of predicting or analyzing therapeutic synergy is illustrated by the fact that the 6 plants that were added to the combination therapy in this experiment were the ones the exhibited the lowest acceptable in vitro antibacterial activity in the original assay. Table 6: CD4 Counts per Month
Figure imgf000082_0001
By comparison with the results achieved with the compositions having the disclosed compounds, in a study conducted on subjects being treated with HAART in Moi University Teaching Hospital and utilizing the Academic Model for Prevention and Treatment of HIV (AMPATH), the CD4 count increases were gradual, generally taking several years to reach above 500 (see Table 7). The subjects were treated with conventional antiretroviral (ARV) therapy, consisting of twice daily dosing of Stavudine, Lamivudine and Nevirapine (d4T-3TC-NVP). Other ARV regimes include treatment with combinations consisting of ZDV-3TC-NVP, d4T-3TC-EFV and ZDV-3TC-EFV (wherein ZDV is Zidovudine and EFV is Efavirenz). Treatment guidelines are provided in the publication “Integrated Management of Adolescent and Adult Illness,” published in January 2004 by the World Health Organization. ARV therapy subjects are not known to reverse their seroconversion status, and among those listed in Table 7, none did so. Table 7: Results of CD4 Count Increases in Subjects Under Conventional ARV Therapy at Moi University; For Comparison With Those Achieved With the Instant Invention
Figure imgf000083_0001
The herbal composition was approved as complementary medicine No. 22345 by the Kenya Pharmacy and Poisons Board under the trade name “Maximum Immune Booster” in July, 2014 (Republic of Kenya, Ministry of Health, Pharmacy and Poisons Board, July 21 2014). In 2015, scientists at the Kenya Medical Research Institute tested the cytotoxicity of Maximum Immune Booster, under the name “Kericho Herbal Compound”, (Songok, et al. 2015), and found it to be safe and non-cytotoxic to human cells. Most recently, in December, 2020, the Kenya Pharmacy and Poisons Board once again confirmed the renewal of the complementary medicine registration (Republic of Kenya, Ministry of Health, Pharmacy and Poisons Board, Invoice of December 9, 2020). Over the years, and under these approvals, Applicants treated hundreds of HIV/AIDS patients. Some were treated with the herbal composition alone, while in other cases, the herbal treatment was used as an adjuvant therapy to HAART. Nearly all of the patients’ viral loads became undetectable in a matter of months. Among patients who took the herbal medicine alone, at least 12 sero-reversed, and became HIV-negative. The medicine was used safely and effectively by pregnant women, and with reduced doses, by infants and children as well.
COVID-19 therapy with the intant invention As the COVID-19 pandemic intensified, Applicants speculated about whether the herbal composition might be helpful in treatment of the disease. After the Kenyan government confirmed the ongoing validity of the Pharmacy and Poisons Board registration, Applicants decided to embark upon a pilot study in the Philippines, where Dr. Maria Medina and Dr. Mitch Medina had come to live. For the purpose of the pilot study, Applicants prepared capsules containing a hydroethanolic extract of the herbal composition. This formulation was given the name “CAREVID”, to distinguish it from the aqueous extracts previously used by applicants to treat HIV/AIDS, under the name “Maximum Immune Booster”. Each size 0 capsule contained the hydroethanolic extract of approximately 22 mg. of a dried powdered herbal composition of the 14 herbs referred to in Table 4 above. The extract was obtained from two successive two-hour heated decoctions of the same 100 gm. of dried powdered herbal composition in 3 liters of fresh solvent mixture each time, said solvent mixture containing 5 parts water to 1 one part ethanol, at a temperature slightly below boiling. The undissolved residue of the said 100 gm. of said dried powdered herbal composition that had been used for the two decoctions was removed from the solution by filtration, and discarded. The resultant filtered solution was compounded and solidified with 300 gm. each of hydroxyethyl cellulose and corn starch, and 11.25 gm. of magnesium stearate. The composite mixture was dried and pulverized, and used to fill conventional size 0 capsules. The aforesaid details of the compounding process are appropriate for the small batches prepared by applicants for the pilot study, but they are not limitative, and are given for convenience only. Many other methods of preparing a therapeutic composition from the aforesaid herbs will occur to those skilled in the art. For the following discussion of treatment of COVID-19 patients with CAREVID, it is significant to note only that each capsule administered to a patient contains approximately 22 mg. of dried powdered hydroethanolic herbal extract. The hydroethanolic extraction method was chosen by applicants as a way to increase the amount terpenoid compounds present in the extract, because terpenoids are not hydrophilic and are underrepresented in an aqueous extract. However, the extraction method used by Applicants in the preparation of CAREVID is not limitative, and other methods of extraction could be deployed by those skilled in the art to make an effective medicine from the 14 plants Table 4, or to synthesize or otherwise obtain, combine, and compound pharmaceutically-active isolated chemicals disclosed in the instant application. As is well known in the art, COVID-19 symptomatology is staged as: 1) asymptomatic or pre-symptomatic; 2) mild; 3) moderate; 4) severe; and 5) critical. Detailed discussion of COVID-19 stages and their associated symptoms is given, inter alia, at National Institutes of Health, 2021, October 19; Lowth, M. (Patient, 2020, April 20; and Jarvis (Patient, 2021, December 1). A brief summary of the characteristics and course of treatment of 32 COVID-19 cases in 31 patients is given in Table 8 below. One patient was treated twice: once prior to vaccination, and again for a breakthrough infection, aftet recovery from the initial infection and subsequent vaccination. All patients were informed of the experimental nature of the treatment, and agreed to receive it. Table 8 : Summary of COVID-19 Patient Characteristics and Course of Treatment
Figure imgf000087_0001
Figure imgf000088_0001
0 i i
Figure imgf000089_0001
Figure imgf000090_0001
Figure imgf000091_0001
23) k d h h/ ld f l ild CO i d O
Figure imgf000092_0001
Figure imgf000093_0001
Figure imgf000094_0002
Table 9: Key to Abbreviations used in Table 8
Figure imgf000094_0001
As can be seen from the fifth column of Table 8 above, NONE of the patients experienced clinical progression of their illness once treatment with CAREVID was initiated. This held true in all stages of the disease; across all age groups; in the presence of various comorbidities; in vaccinated, partially vaccinated and unvaccinated patients; and in initial and breakthrough cases, of suspected different virus variants. Although the sample of patients in this pilot study is small, this result has not been achieved with any other COVID-19 treatment or therapeutic, actual or proposed. The participants in the study were not cherry-picked in any way. Any person who: 1) presented him- or herself to Dr. Maria Medina over the course of the study; 2) had a positive COVID-19 test; and 3) was willing to try the treatment; was enrolled. The participants were from Tanauan City, Batangas, Philippines, Dr. Maria Medina’s current residence, and its environs. An estimate of the probability of the result of this pilot study having occurred by chance is difficult to compute. There is no generally-accepted figure for the likelihood of clinical progression of COVID-19. The number varies with age, vaccination status, comorbidities, the virus variant involved, locus and type of care, and other factors. However, it is possible to deploy an educated guess that 21% of all confirmed COVID-19 cases progress clinically in some way. A Chinese study on the original wild-type virus showed 21% clinical progression in 323 mild-to-moderate, unvaccinated, hospitalized patients, (10 more were already severe or critical when admitted). All of the 333 cases had previously progressed from asymptomatic, or they would not have been admitted to the hospital. (Wang et. al., 2020, July 3). The 21% figure is probably a low estimate for total clinical progression of confirmed COVID-19 cases, since the first stage of clinical progression was not tallied in the Wang et. al. analysis. Under the 21%-clinical progression assumption, the chi-square calculation for goodness of fit yields a value of 8.506. This corresponds to a p-value of .00354, indicating extremely high statistical significance of the results of this pilot study. Even if the overall probability of clinical progression is arbitrarily reduced to 11%, and the likelihood of non- progression is correspondingly increased to 89%, the chi-square value is 3.995, equating to a p-value of .04673, which validates the results of the instant study at a statistically significant confidence level of 95%-plus. Larger studies are required to generate more definitive numbers. However, there is no serious question that the overall risk of clinical progression in confirmed COVID-19 cases is greater than Applicants’ low-end hypothesis of 11%, in a sample in which 20 out of the 32 cases occurred in then-unvaccinated individuals. Future forward, the latest figures from a very large sample of 211,000 COVID cases in South Africa, in the presence of the Omicron variant, indicates that Applicants’ 11% lower hypothetical clinical progression rate is very much less than current and future progression realities (Discovery Health, 2021, December 14). Because CAREVID has extremely high efficacy against the very different HIV virus, as well as SARS-CoV-2, its effectiveness against COVID-19 is likely to be broad enough to not be dented by Omicron, or future SARS-CoV-2 variants. Further, it has been theorized that Omicron and other variants of SARS-COV may have arisen in the immunocompromised HIV/AIDS- positive population of Southern Africa, and/or elsewhere (Rigby & Brown, November 26, 2021; Cele et. al 2021, December 7, 2021). Because of CAREVID’s dual efficacy against HIV/AIDS and COVID- 19, widespread adoption of it as an HIV therapy actually may help reduce the proliferation of new SARS-COV-2 variants. The course of therapy with CAREVID for COVID-19 is short, and no side effects have been observed. It is also worth noting that CAREVID’s predecessor formulation, Maximum Immune Booster, has safely been administered to hundreds of HIV-positive patients, including pregnant women, infants and children, for periods of months and years, without significant side effects. All patents and other references cited in the specification are indicative of the level of skill of those skilled in the art to which the invention pertains, and are incorporated by reference in their entireties, including any tables and figures, to the same extent as if each reference had been incorporated by reference in its entirety individually. One skilled in the art would readily appreciate that the present invention is well adapted to obtain the ends and advantages mentioned, as well as those inherent therein. The methods, variances, and compositions described herein as presently representative of preferred embodiments are exemplary and are not intended as limitations on the scope of the invention. Changes therein and other uses will occur to those skilled in the art and are encompassed within the spirit of the invention, which is defined by the scope of the claims. The inventions illustratively described herein may suitably be practiced in the absence of any element or elements, limitation or limitations, not specifically disclosed herein. Thus, for example, the terms “comprising”, “including,” containing”, etc., shall be read expansively and without limitation. Additionally, the terms and expressions employed herein have been used as terms of description and not of limitation, and there is no intention, in the use of such terms and expressions, of excluding any equivalents of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the invention claimed. Thus, it should be understood that, although the present invention has been specifically disclosed by preferred embodiments and optional features, modification and variation of the inventions embodied therein herein disclosed may be resorted to by those skilled in the art, and that such modifications and variations are considered to be within the scope of this invention. The invention has been described broadly and generically herein. Each of the narrower species and subgeneric groupings falling within the generic disclosure also form part of the invention. This includes the generic description of the invention with a proviso or negative limitation removing any subject matter from the genus, regardless of whether or not the excised material is specifically recited herein. The plant parts described in the specification are those in which in the experience of the inventors, the highest concentration of beneficial ingredients is to be found. However, it will be apparent to those skilled in the art that the same or other beneficial compounds may be found in other parts of the recited plants not specifically disclosed herein, and that therefore, any composition comprised of any part or parts of the recited plants which includes Dovyalis abyssinica and Clutia robusta is within the scope of the invention. It is understood by those skilled in the art that the identity of the most bioactive compounds in a botanical therapeutic can unpredictable, and the dynamics of the therapeutic synergy difficult to analyze (Ruiz et. al, 2016, July 26). Therefore, the presence of all of the isolated compounds may not be necessary in a therapeutically-effective pharmaceutical composition, and such compositions containing less than all of applicants’ isolated compounds are within the scope of the invention. While some detailed embodiments have been illustrated and described, it should be understood that such detailed embodiments are merely exemplary, and changes and modifications can be made therein in accordance with ordinary skill in the art without departing from the invention in its broader aspects as defined in the following claims. Other embodiments are within the following claims. In addition, where features or aspects of the invention are described in terms of Markush groups, those skilled in the art will recognize that the invention is also thereby described in terms of any individual member or subgroup of members of the Markush group.

Claims

What is claimed is: 1. A composition comprising Dovyalis abyssinica and Clutia robusta for the treatment of COVID-19.
2. The composition of claim 1, further comprising at least one of the following plants: Prunus africana, Croton macrostachyus, Acacia nilotica, Rhamnus prinoides, Adenia gummifera, Asparagus africanus, Anthocleista grandiflora, Plantago palmata, Clematis hirsuta, Ekebergia capensis, Bersama abyssinica, or Periploca linearifolia.
3. The composition of claim 1, further comprising all of the following plants: Prunus africana, Croton macrostachyus, Acacia nilotica, Rhamnus prinoides, Adenia gummifera, Asparagus africanus, Anthocleista grandiflora, Plantago palmata, Clematis hirsuta, Ekebergia capensis, Bersama abyssinica, and Periploca linearifolia.
4. A composition comprising root of Dovyalis abyssinica and root of Clutia robusta for the treatment of COVID-19.
5. The composition of claim 4, further comprising at least one of the following plant parts: stem bark of Prunus africana, stem bark of Croton macrostachyus, stem bark of Acacia nilotica, root of Rhamnus prinoides, root of Adenia gummifera, root of Asparagus africanus, stem bark of Anthocleista grandiflora, whole plant of Plantago palmata, root of Clematis hirsuta, stem bark of Ekebergia capensis, stem bark of Bersama abyssinica, or root of Periploca linearifolia.
6. The composition of claim 4, further comprising all of the following plant parts: stem bark of Prunus africana, stem bark of Croton macrostachyus, stem bark of Acacia nilotica, roots of Rhamnus prinoides, roots of Adenia gummifera, roots of Asparagus africanus, stem bark of Anthocleista grandiflora, whole plant of Plantago palmata, roots of Clematis hirsuta, stem bark of Ekebergia capensis, stem bark of Bersama abyssinica, and root of Periploca linearifolia.
7. A composition comprising a combination of extracts of root of Dovyalis abyssinica and root of Clutia robusta for the treatment of COVID-19.
8. The composition of claim 7, further comprising an extract of at least one of the following: stem bark of Prunus africana, stem bark of Croton macrostachyus, stem bark of Acacia nilotica, root of Rhamnus prinoides, root of Adenia gummifera, root of Asparagus africanus, stem bark of Anthocleista grandiflora, whole plant of Plantago palmata, root of Clematis hirsuta, stem bark of Ekebergia capensis, or stem bark of Bersama abyssinica, or root of Periploca linearifolia.
9. The composition of claim 7, further comprising extracts of all of the following: stem bark of Prunus africana, stem bark of Croton macrostachyus, stem bark of Acacia nilotica, root of Rhamnus prinoides, root of Adenia gummifera, root of Asparagus africanus, stem bark of Anthocleista grandiflora, whole plant of Plantago palmata, root of Clematis hirsuta, stem bark of Ekebergia capensis, or stem bark of Bersama abyssinica, and root of Periploca linearifolia.
10. The composition of claim 7 in which the extracts comprise water extracts.
11. The composition of claim 8 in which the extracts comprise water extracts.
12. The composition of claim 9 in which the extracts comprise water extracts.
13. The composition of claim 7 in which the extracts comprise ethanol extracts.
14. The composition of claim 8 in which the extracts comprise ethanol extracts.
15. The composition of claim 9 in which the extracts comprise ethanol extracts.
16. A composition for the treatment of COVID-19 comprising at least one of the following alkaloid compounds: a) N-Methyl-L-tryptophan; b) 1,2-Methylenedioxy-9-hydroxy-10- methoxynoraporphine; c) 6-(1,2,3,4-Tetrahydro-6,7-dimethoxy-2-methyl-1- isoquinolinyl)furo[3,4-e]-1,3-benzodioxol- 8(6H)-one; or d) [1,α,3β(E),5α,6α,7α]-2-Methyl-2-butenoic acid- 6,7-dihydroxy-8-methyl-8-azabicyclo[3.2.1]oct- 3-yl ester; and at least one of the following alkaloid compounds: a) (6aS)-9-[4,5-Dimethoxy-2-[[(1S)-1,2,3,4- tetrahydro-6,7-dimethoxy-2-methyl-1- isoquinolinyl]methyl]phenoxy]-5,6,6a,7- tetrahydro-1,2,10-trimethoxy-6-methyl-4H- dibenzo[de,g]quinoline; b) 3β-(Hydroxymethyl)-2α-methyl-4 β-[(9-methyl-9H- pyrido[3,4-b]indol-1-yl)methyl]-2H-pyran-5- carboxylic acid methyl ester; or c) (3aS-cis)-1,2,3,3a,8,8a-Hexahydro-1,3a,8- trimethylpyrrolo[2,3-b]indol-5-ol methylcarbamate (ester).
17. A composition for the treatment of COVID-19 comprising all of the following alkaloid compounds: a) N-Methyl-L-tryptophan; b) 1,2-Methylenedioxy-9-hydroxy-10- methoxynoraporphine; c) 6-(1,2,3,4-Tetrahydro-6,7-dimethoxy-2-methyl-1- isoquinolinyl)furo[3,4-e]-1,3-benzodioxol- 8(6H)-one; and d) [1,α,3β(E),5α,6α,7α]-2-Methyl-2-butenoic acid- 6,7-dihydroxy-8-methyl-8-azabicyclo[3.2.1]oct- 3-yl ester; and: a) (6aS)-9-[4,5-Dimethoxy-2-[[(1S)-1,2,3,4- tetrahydro-6,7-dimethoxy-2-methyl-1- isoquinolinyl]methyl]phenoxy]-5,6,6a,7- tetrahydro-1,2,10-trimethoxy-6-methyl-4H- dibenzo[de,g]quinoline; b) 3β-(Hydroxymethyl)-2α-methyl-4 β-[(9-methyl-9H- pyrido[3,4-b]indol-1-yl)methyl]-2H-pyran-5- carboxylic acid methyl ester; and c) (3aS-cis)-1,2,3,3a,8,8a-Hexahydro-1,3a,8- trimethylpyrrolo[2,3-b]indol-5-ol methylcarbamate (ester).
18. The composition of claim 16 or 17, further comprising at least one of the following alkaloid compounds: a) (1α,2β)-3,12-Dihehydro-9,10- [methylenebis(oxy)]galanthan-1,2-diol; b) (3β,12α)-Solanid-5-ene-3,12-diol; c) 1-(6-methoxy-4-quinolyl)-3-(3-vinyl-4- piperidyl)-1-propanone; d) (E,E,Z)-N-isobutyl-2,6,8-decatrienamide; e) 2,3,5,6-tetramethoxyphenanthro- [9,10:6’,7’]indolizidine; f) 5,7,8,15-Tetrahydro-3,4-dimethoxy-6- methylbenzo[e][1,3]dioxolo[4,5-k][3]benzazecin- 14(6H)-one; g) (1S,6S,7R,8R,8aR)-Octahydro-indolizinetetrol; h) (3S,4R)-Dihydro-3-[(R)-hydroxyphenylmethyl]-4- [(1-methyl-1H-imidazol-5-yl)methyl]-2(3H)- furanone; i) (3S-cis)-3-Ethyldihdroxy-4-[(-methyl-1H- imidazol-5-yl)methyl]-2(3H)-furanone; j) (S)-4-Ethyl-4-hydroxy-1H- pyrano[3'4':6,7]indolizino[1,2-b]quinoline- 3,14(4H, 12H)-dione; k) 1,2,3,4-Tetrahydro-6,7-dimethoxy-8- isoquinolinol; l) 1,2,3,4-Tetrahydro-6,7-dimethoxy-1-methyl-8- isoquinolinol; m) N-(7S)-5,6,7,9-Tetrahydro-1,2,3,10- tetramethoxy-9-oxobenzo[a]heptalen-7- yl]acetamide; n) 1αH,5αH-tropan-3α-ol atropate; o) 1,2-(methylenedioxy)-6aβ-aporphin-11-ol; p) (16α, 17α)-17-Hydroxyyohimban-16-carboxylic acid methyl ester; q) trans-8-methyl-N-vanillyl-6-nonenamide; r) 1,2-(methylenedioxy)aporphine; s) (1R-trans)-2,3,5,7a-Tetrahydro-1-hydroxy-1H- pyrrolizine-7-methan; t) [1R-(1α,2E,4aα,4bβ,8aα,10aβ)]-(Dodecahydro-7- hydroxy-1,4b,8,8-tetramethyl-10-oxo-2(H)- phenanthrenylidene) acetic acid 2- (dimethylamino)ethyl ester; u) (3α,14β,16α)-14,15-Dihydro-14- hydroxyeburnamenine-14-carboxylic acid methyl ester; v) 1,10-Dimethoxy-6aα-aporhine-2,9-diol; u) 6,7,12b,13-Tetrahydro-4H- bis[1,3]benzodioxolo[5,6-a:4',5'-g]quinolizine; v) (8β)-8-methoxy-16-methyl-2,3:10,11- bis[methylenebis(oxy)]rheadan; w) 6',7',10,11-Tetramethoxyemetan; x) 3-(-Benzoyloxy)-8-methyl-8- azabicyclo[3.2.1]octane-2-carboxylic acid; y) 8,13,13b,14-Tetrahydro-14- methylindolo[2',3':3,4]pyrido-[2,1-b]quinazolin- 5(7H)-one; z) 6',12'-Dimethoxy-2,2'-dimethyl-6,7- [methylenebis(oxy)]-oxyacanthan; aa) 4-[[(1R)-1,2,3,4-Tetrahydro-6,7-dimethoxy-2- methyl-1-isoquinolinyl]methyl]-2-[4-[[(1R)- 1,2,-3,4-tetrahydro-6,7-dimethoxy-2-methyl-1- isoquinolinyl]methyl]-phenoxylphenol; bb) 5,11-Dimethyl-6H-pyrido[4,-3b]carbazole; cc) 6,7-Dihydro-1,2,3,10-tetramethoxy-7- (methylamino)benzo[a]heptalen-9(5H)-one; dd) (1α)-2,3-Didehydro-7-methoxycrinan-1-ol; or ee) (1α,3α)-7-methoxycrinan-1,3-diol.
19. The composition of claim 16 or 17, further comprising all of the following alkaloid compounds: a) (1α,2β)-3,12-Dihehydro-9,10- [methylenebis(oxy)]galanthan-1,2-diol; b) (3β,12α)-Solanid-5-ene-3,12-diol; c) 1-(6-methoxy-4-quinolyl)-3-(3-vinyl-4- piperidyl)-1-propanone; d) (E,E,Z)-N-isobutyl-2,6,8-decatrienamide; e) 2,3,5,6-tetramethoxyphenanthro- [9,10:6’,7’]indolizidine; f) 5,7,8,15-Tetrahydro-3,4-dimethoxy-6- methylbenzo[e][1,3]dioxolo[4,5-k][3]benzazecin- 14(6H)-one; g) (1S,6S,7R,8R,8aR)-Octahydro-indolizinetetrol; h) (3S,4R)-Dihydro-3-[(R)-hydroxyphenylmethyl]-4- [(1-methyl-1H-imidazol-5-yl)methyl]-2(3H)- furanone; i) (3S-cis)-3-Ethyldihdroxy-4-[(-methyl-1H- imidazol-5-yl)methyl]-2(3H)-furanone; j) (S)-4-Ethyl-4-hydroxy-1H- pyrano[3'4':6,7]indolizino[1,2-b]quinoline- 3,14(4H, 12H)-dione; k) 1,2,3,4-Tetrahydro-6,7-dimethoxy-8- isoquinolinol; l) 1,2,3,4-Tetrahydro-6,7-dimethoxy-1-methyl-8- isoquinolinol; m) N-(7S)-5,6,7,9-Tetrahydro-1,2,3,10- tetramethoxy-9-oxobenzo[a]heptalen-7- yl]acetamide; n) 1αH,5αH-tropan-3α-ol atropate; o) 1,2-(methylenedioxy)-6aβ-aporphin-11-ol; p) (16α, 17α)-17-Hydroxyyohimban-16-carboxylic acid methyl ester; q) trans-8-methyl-N-vanillyl-6-nonenamide; r) 1,2-(methylenedioxy)aporphine; s) (1R-trans)-2,3,5,7a-Tetrahydro-1-hydroxy-1H- pyrrolizine-7-methan; t) [1R-(1α,2E,4aα,4bβ,8aα,10aβ)]-(Dodecahydro-7- hydroxy-1,4b,8,8-tetramethyl-10-oxo-2(H)- phenanthrenylidene) acetic acid 2- (dimethylamino)ethyl ester; u) (3α,14β,16α)-14,15-Dihydro-14- hydroxyeburnamenine-14-carboxylic acid methyl ester; v) 1,10-Dimethoxy-6aα-aporhine-2,9-diol; u) 6,7,12b,13-Tetrahydro-4H- bis[1,3]benzodioxolo[5,6-a:4',5'-g]quinolizine; v) (8β)-8-methoxy-16-methyl-2,3:10,11- bis[methylenebis(oxy)]rheadan; w) 6',7',10,11-Tetramethoxyemetan; x) 3-(-Benzoyloxy)-8-methyl-8- azabicyclo[3.2.1]octane-2-carboxylic acid; y) 8,13,13b,14-Tetrahydro-14- methylindolo[2',3':3,4]pyrido-[2,1-b]quinazolin- 5(7H)-one; z) 6',12'-Dimethoxy-2,2'-dimethyl-6,7- [methylenebis(oxy)]-oxyacanthan; aa) 4-[[(1R)-1,2,3,4-Tetrahydro-6,7-dimethoxy-2- methyl-1-isoquinolinyl]methyl]-2-[4-[[(1R)- 1,2,-3,4-tetrahydro-6,7-dimethoxy-2-methyl-1- isoquinolinyl]methyl]-phenoxylphenol; bb) 5,11-Dimethyl-6H-pyrido[4,-3b]carbazole; cc) 6,7-Dihydro-1,2,3,10-tetramethoxy-7- (methylamino)benzo[a]heptalen-9(5H)-one; dd) (1α)-2,3-Didehydro-7-methoxycrinan-1-ol; and ee) (1α,3α)-7-methoxycrinan-1,3-diol.
20. A composition for the treatment of COVID-19 comprising at least one of the following terpenoid compounds: a) [1R-(1α,4aβ,4bα,10aα)]-1,2,3,4,4a,4b,5,9,10,10a- Decahydro-1,4a-dimethyl-7-(1-methylethyl)-1- phenanthrenecarboxylic acid; or b) β-Cadinene; and at least one of the following terpenoid compounds: a) [1aR-(1aα,4α,4aβ,7α,7a β,7bα)]-Decahydro- 1,1,4,7-tetramethyl-1H-cycloprop[e]azulen-4-ol; or b) 1-(Acetylloxy)-1,2-dihydroobacunoic acid ε- lactone.
21. A composition for the treatment of COVID-19 comprising all of the following terpenoid compounds: a) [1R-(1α,4aβ,4bα,10aα)]-1,2,3,4,4a,4b,5,9,10,10a- Decahydro-1,4a-dimethyl-7-(1-methylethyl)-1- phenanthrenecarboxylic acid; b) β-Cadinene; and: a) [1aR-(1aα,4α,4aβ,7α,7a β,7bα)]-Decahydro- 1,1,4,7-tetramethyl-1H-cycloprop[e]azulen-4-ol; b) 1-(Acetylloxy)-1,2-dihydroobacunoic acid ε- lactone.
22. The composition of claim 20 or 21, further comprising at least one of the following terpenoid compounds: a) [1R-[1α,3aα,4β(Z),6β,8β(Z),8aβ]-2-Methyl-2- butenoic acid decahydro-1,6-dihydroxy-3a,6- dimethyl-1-(1-methylethyl)-5-oxo-4,8- azulenediyl ester; b) [3aR-(3aα,4β,9aα,9bβ)]-3,3a,4,5,9a9b-Hexahydro- 4-hydroxy-9-(hydroxymethyl)-6-methyl-3- methyleneazuleno[4,5-b]furan-2,7-dione ; c) 1,6β-dihydroxy-4-oxo-10αH-ambrosa-2,11(13)- dien-12-oic acid; d) 13-cis-Retinoic acid; e) [4S-(4α,4aβ,7β,7aβ)]-Hexahydro-4,7- dimethylcyclopentaneacetic acid δ-lactone; f) (3’S-trans)-2’,3’-Dihydro-3,6-dihydroxy- 2’,2’,4’,6’-tetramethylspiro[cyclopropane-1,5’- [5H]inden]-7’(6’H)-one; g) 6α,8β-dihydroxy-4-oxo-ambrosa-2,11(13)-dien-12- oic acid 12,8-lactone; h) 9,13-epoxylabd-7-en-15-oic acid; i) (1β)-1-Hydroxyginkgolide A; j) 18β-glycyrrhetinic acid; k) [5aS-(5aα,9aβ,9bα)]-5,5a,6,7,8,9,9a,9b- Octahydro-6,6,9a,trimethylnaphtho[1,2-c]furan- 1(3H)-one; l) 13α-methyl-13-vinylpodocarp-8(14)-ene-15-oic acid; m) 4,5α-epoxy-6β-hydroxy-germacra-1(10),11(13)- dien-12-oic acid γ-lactone; n) 2,3,4,5,8,8a-hexahydro-3-isopropyl-6,8a- dimethyl-3a(1H-azulenol); o) (3β)-3-Hydroxyolean-12-en-28-oic acid; or p) 1,3-isopropylpodocarpa-8,13-dien-15-oic acid.
23. The composition of claim 20 or 21, further comprising all of the following terpenoid compounds: a) [1R-[1α,3aα,4β(Z),6β,8β(Z),8aβ]-2-Methyl-2- butenoic acid decahydro-1,6-dihydroxy-3a,6- dimethyl-1-(1-methylethyl)-5-oxo-4,8- azulenediyl ester; b) [3aR-(3aα,4β,9aα,9bβ)]-3,3a,4,5,9a9b-Hexahydro- 4-hydroxy-9-(hydroxymethyl)-6-methyl-3- methyleneazuleno[4,5-b]furan-2,7-dione; c) 1,6β-dihydroxy-4-oxo-10αH-ambrosa-2,11(13)- dien-12-oic acid; d) 13-cis-Retinoic acid; e) [4S-(4α,4aβ,7β,7aβ)]-Hexahydro-4,7- dimethylcyclopentaneacetic acid δ-lactone; f) (3’S-trans)-2’,3’-Dihydro-3,6-dihydroxy- 2’,2’,4’,6’-tetramethylspiro[cyclopropane-1,5’- [5H]inden]-7’(6’H)-one; g) 6α,8β-dihydroxy-4-oxo-ambrosa-2,11(13)-dien-12- oic acid 12,8-lactone; h) 9,13-epoxylabd-7-en-15-oic acid; i) (1β)-1-Hydroxyginkgolide A; j) 18β-glycyrrhetinic acid; k) [5aS-(5aα,9aβ,9bα)]-5,5a,6,7,8,9,9a,9b- Octahydro-6,6,9a,trimethylnaphtho[1,2-c]furan- 1(3H)-one; l) 13α-methyl-13-vinylpodocarp-8(14)-ene-15-oic acid; m) 4,5α-epoxy-6β-hydroxy-germacra-1(10),11(13)- dien-12-oic acid γ-lactone; n) 2,3,4,5,8,8a-hexahydro-3-isopropyl-6,8a- dimethyl-3a(1H-azulenol); o) (3β)-3-Hydroxyolean-12-en-28-oic acid; or p) 1,3-isopropylpodocarpa-8,13-dien-15-oic acid.
24. A composition for the treatment of COVID-19 comprising at least one of the following steroid glycoside compounds: a) (3β,5β)-3-[(O-β-D-Glucopyranosyl-(1→6)-O-D- glucopyranosyl-(1→4)-6-deoxy-3-O-methyl-α-L- glucopyranosyl)oxy]-14-hydroxy-19-oxocard- 20(22)-enolide; or b) (3β,5α,25R)-Spirostan-3-ol; and at least one of the following steroid glycoside compounds: a) 3β-(diginosyloxy)-12α,20α-epoxy-14β,17α-pregn- 5-ene-11,15-dione; or b) 3β,5β,25S)-Spirostan-3-ol.
25. A composition for the treatment of COVID-19 comprising all of the following steroid glycoside compounds: a) (3β,5β)-3-[(O-β-D-Glucopyranosyl-(1→6)-O-D- glucopyranosyl-(1→4)-6-deoxy-3-O-methyl-α-L- glucopyranosyl)oxy]-14-hydroxy-19-oxocard- 20(22)-enolide; and b) (3β,5α,25R)-Spirostan-3-ol; and: c) 3β-(diginosyloxy)-12α,20α-epoxy-14β,17α-pregn- 5-ene-11,15-dione; and d) 3β,5β,25S)-Spirostan-3-ol.
26. The composition of claim 24 or 25, further comprising at least one of the following steroid glycoside compounds: a) (3β,5β,16β)-3-[(6-Deoxy-4-O- β-D-glucopyranosyl-3-O- methyl- β-D-galactopyranosyl)oxy]-14,16- dihydroxycard-20(22)-enolide; b) (3β)-3-[(6-Deoxy-4-O-β-D-glucopyranosyl-α-L- mannopyranosyl)oxy]-14-hydroxybufa-4,20,22- trienolide; c) (3β,25R)-Spirost-5-en-3-ol; d) (3α,5α,15β,25R)-Spirostan-3,15-diol; e) (3β,12β,14β)-3-[(O-6-Deoxy-3-O-methyl-β-D- glucopyranosyl-(1→4)-O-2,6-dideoxy-3- O-methyl-β-D- ribo-hexopyranosyl-(1→4)-2,6-dideoxy-3-O-methyl-β-D- ribo-hexopyranosyl)oxy]-14-hydroxy-12-[[(2E)-2- methyl-1-oxo-2-butenyl]oxy]pregn-5-en-20-one; f) (3β,12β,14β)-3-[(O-6-Deoxy-3-O-methyl-α-D- glucopyranosyl-(1→4)-O-2,6-dideoxy-3- O-methyl-β-D- ribo-hexopyranosyl-(1→4)-2,6-dideoxy-3-O-methyl-β-D- ribo-hexopyranosyl)oxy]-14-hydroxy-12-[[(2E)-2- methyl-1-oxo-2-butenyl]oxy]pregn-5-en-20-one; g) (1β,3β,5β,11α)-3-[(6-Deoxy-α-L-mannopyranosyl)oxy]- 1,5,11,14,19-pentahydroxycard-20(22)-enolide; h) (1α,3β,5β,11α)-3-[(6-Deoxy-α-L-mannopyranosyl)oxy]- 1,5,11,14,19-pentahydroxycard-20(22)-enolide; i) (3β,15α,25R)-26-(Acetyloxy)-3-hydroxycholest-5-en- 15-yl-2-(acetylamino)-2-deoxy-β-D-glucopyranoside; j) (3α,15α,25R)-26-(Acetyloxy)-3-hydroxycholest-5-en- 15-yl-2-(acetylamino)-2-deoxy-β-D-glucopyranoside; k) 3β-rhamnosido-14β-hydroxy-bufatrienolide; l) 2-O-β-D-glucopyranosylcucurbitacin; m) Strophanthidin α-L-rhamnoside;n) (3β,5β,16β)-16- (Acetyloxy)-3-[(2,6-Dideoxy-3-O-methyl-α-L-arabino- hexopyranosyl)oxy]-14-hydroxycard-20(22)-enolide; o) (4α)-13-[(2-O-β-D-Glucopyranosyl-β-D- glucopyranosyl)oxy]kaur-16-en-18-oic-β-D- glucopyranosyl ester; p) (3β,5 α,25R)-Spironstan-3-ol; q) (3β,5β)-3-[(6-Deoxy-3-O-methyl-α-L- glucopyranosyl)oxy]-14-hydroxycard-20(22)-enolide; r) (3β,5β,16β)-3-[(6-Deoxy-α-L-mannopyranosyl)oxy]- 14,16-dihydroxy-19-oxocard-20(22)-enolide; s) (3β,5α,6α,25R)-Spirostan-3,6-diol; t) (3β,5β,16β)-3-[(6-Deoxy-4-O- β-D-glucopyranosyl-3-O- methyl-β-D-galactopyranosyl)oxy]-14,16- dihydroxycard-20(22)-enolide; u) (2β,3α, 5α,15β,25R)-Spirostan-2,3,15-triol; 27. The composition of claim 24 or 25, further comprising all of the following steroid glycoside compounds: a) (3β,5β,16β)-3-[(6-Deoxy-4-O- β-D-glucopyranosyl-3-O- methyl- β-D-galactopyranosyl)oxy]-14,16- dihydroxycard-20(22)-enolide; b) (3β)-3-[(6-Deoxy-4-O-β-D-glucopyranosyl-α-L- mannopyranosyl)oxy]-14-hydroxybufa-4,20,22- trienolide; c) (3β,25R)-Spirost-5-en-3-ol; d) (3α,5α,15β,25R)-Spirostan-3,15-diol; e) (3β,12β,14β)-3-[(O-6-Deoxy-3-O-methyl-β-D- glucopyranosyl-(1→4)-O-2,6-dideoxy-3- O-methyl-β-D- ribo-hexopyranosyl-(1→4)-2,6-dideoxy-3-O-methyl-β-D- ribo-hexopyranosyl)oxy]-14-hydroxy-12-[[(2E)-2- methyl-1-oxo-2-butenyl]oxy]pregn-5-en-20-one; f) (3β,12β,14β)-3-[(O-6-Deoxy-3-O-methyl-α-D- glucopyranosyl-(1→4)-O-2,6-dideoxy-3- O-methyl-β-D- ribo-hexopyranosyl-(1→4)-2,6-dideoxy-3-O-methyl-β-D- ribo-hexopyranosyl)oxy]-14-hydroxy-12-[[(2E)-2- methyl-1-oxo-2-butenyl]oxy]pregn-5-en-20-one; g) (1β,3β,5β,11α)-3-[(6-Deoxy-α-L-mannopyranosyl)oxy]- 1,5,11,14,19-pentahydroxycard-20(22)-enolide; h) (1α,3β,5β,11α)-3-[(6-Deoxy-α-L-mannopyranosyl)oxy]- 1,5,11,14,19-pentahydroxycard-20(22)-enolide; i) (3β,15α,25R)-26-(Acetyloxy)-3-hydroxycholest-5-en- 15-yl-2-(acetylamino)-2-deoxy-β-D-glucopyranoside; j) (3α,15α,25R)-26-(Acetyloxy)-3-hydroxycholest-5-en- 15-yl-2-(acetylamino)-2-deoxy-β-D-glucopyranoside; k) 3β-rhamnosido-14β-hydroxy-bufatrienolide; l) 2-O-β-D-glucopyranosylcucurbitacin; m) Strophanthidin α-L-rhamnoside;n) (3β,5β,16β)-16- (Acetyloxy)-3-[(2,6-Dideoxy-3-O-methyl-α-L-arabino- hexopyranosyl)oxy]-14-hydroxycard-20(22)-enolide; o) (4α)-13-[(2-O-β-D-Glucopyranosyl-β-D- glucopyranosyl)oxy]kaur-16-en-18-oic-β-D- glucopyranosyl ester; p) (3β,5 α,25R)-Spironstan-3-ol; q) (3β,5β)-3-[(6-Deoxy-3-O-methyl-α-L- glucopyranosyl)oxy]-14-hydroxycard-20(22)-enolide; r) (3β,5β,16β)-3-[(6-Deoxy-α-L-mannopyranosyl)oxy]- 14,16-dihydroxy-19-oxocard-20(22)-enolide; s) (3β,5α,6α,25R)-Spirostan-3,6-diol; t) (3β,5β,16β)-3-[(6-Deoxy-4-O- β-D-glucopyranosyl-3-O- methyl-β-D-galactopyranosyl)oxy]-14,16- dihydroxycard-20(22)-enolide; u) (2β,3α, 5α,15β,25R)-Spirostan-2,3,15-triol.
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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7556830B2 (en) * 2005-08-22 2009-07-07 International Patents Holdings, Ltd. Medicinal herbal composition for treating infection
US8067401B2 (en) * 2007-09-06 2011-11-29 International Patent Holdings Llc Compounds and compositions for treating infection
US8697660B2 (en) * 2011-07-22 2014-04-15 International Patent Holdings Llc Compounds and compositions for treating infection

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7556830B2 (en) * 2005-08-22 2009-07-07 International Patents Holdings, Ltd. Medicinal herbal composition for treating infection
US8067401B2 (en) * 2007-09-06 2011-11-29 International Patent Holdings Llc Compounds and compositions for treating infection
US8697660B2 (en) * 2011-07-22 2014-04-15 International Patent Holdings Llc Compounds and compositions for treating infection

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