Comparative Analysis of the Efficiency of Medicinal Plants for the Treatment and Prevention of COVID-19

The COVID-19 pandemic has once again prompted people to resort to the remedies of folk and alternative medicine. Medicinal plants, because of their chemical composition, pharmacological properties, and the action of biologically active substances, can stop and relieve the symptoms of the disease. The purpose of the work is a comparative flora analysis of medicinal plants to identify the most prospective plant and further production of a remedy for the avoidance, treatment, and rehabilitation of COVID-19. The search for prospective medicinal plants was performed by analyzing the literature in online databases: Web of Science, Scopus, Google Scholar, and PubMed, including official WHO media sites. According to recent studies related to COVID-19, a significant number of medicinal plants with anti-inflammatory, antiviral, and immunostimulatory effects have been identified. A comparative study of nine medicinal plants was conducted to determine the most suitable medicinal plant to treat coronavirus infection. According to the results of the comparative analysis, Chamaenerion angustifolium Seg. showed itself as the most prospective medicinal plant with the greatest pharmacological effect compared with other types of medicinal plants. Its therapeutic properties allow physiological relief of 18 symptoms of coronavirus infection. It is advisable to conduct further clinical trials for the treatment and rehabilitation of COVID-19 using preparations from this plant.


Introduction
Te current coronavirus pandemic has shown the importance of providing the nation with efective and safe domestically produced medicines. In this regard, herbal medicines with a wide range of therapeutic action and several advantages in comparison with medicines of synthetic origin are of particular relevance. Herbal medicines are characterized by a relatively low risk of allergy development, a milder therapeutic efect, and safety. Te main selection criteria for herbal raw materials as a source of pharmacologically active compounds are high amount of active agents, availability of raw materials in nature, and simple technology of their cultivation.
Te rapid spread of coronavirus infection has boosted the market demand for medicinal plant raw materials. Tere was a problem of shortage of medicines. Te shortage of drugs was also related to the pandemic because the prices on the world market were infated, and there were difculties with transportation due to closed borders. Te anxiety caused by the side efects of chemical drugs, the desire to create a healthcare system with a more personalized approach, and the public's wide access to health information all contribute to the wider use of alternative medicine. In addition, there is a signifcant list of residual efects after COVID-19 symptoms have occurred, and in some patients, they do not go away after several months. Tere are no drugs that can alleviate these symptoms yet. Terefore, the population has resorted to traditional and alternative medicine.
Plants have been used in folk medicine since ancient times. As is well known, plants contain chemical substances, the action of which is directed to various processes, entering complex interactions with the organism. Medicinal properties of plants are caused by the presence in their organs of active substances (alkaloids, favonoids, glycosides, vitamins, tannins, and coumarin compounds) that have a physiological efect on human and animal organisms or have biological activity against pathogens of various diseases [1,2]. Plants produce aromatic substances, most of which are phenols, and their oxygen-substituting derivatives are useful for health support. For example, one medicinal plant can replace several synthetic drugs and be used in the treatment of diseases of various organs and systems, both the main and related diseases [3]. It has long been established that plants can have diferent efects on the human body.
Alkaloids are plant defense mechanisms against microorganisms, insects, and animals. Some biologically active plant compounds are active against strains of viruses, even those that have adapted to antibiotics.
Flavonoids have been reported to be able to prevent the induction of COX by prostaglandins in infamed tissues. Apigenin is known to reduce the fow of lipids necessary for pain signal transmission. Tus, favonoids reduce infammatory pain by inhibiting receptors and signaling pathways [4].
Te work by da Silva et al. [5] presents the results of the molecular docking of 171 essential oil components with the main protease SARS-CoV-2. Te scientists hypothesized that essential oil components might interact with key protein targets of the disease. As a result, they found that essential oils can potentiate the efects of other antiviral agents or they can provide some relief from the symptoms of infection.
Currently, there is still an active search for efective drugs to treat COVID-19 and eliminate residual symptoms of the disease. Treatment guidelines are constantly changing, the virus mutates, and new symptoms of the disease appear. Te efect of the disease depends on the immune state of the body; complications arise in the presence of concomitant chronic diseases [6]. Herbal remedies have low toxicity compared with synthetic drugs and are used in the pharmaceutical industry because of their powerful biological activity. Because of the action of complex reactions in the body, they contribute to a quick recovery and an easy course of the disease.
Te purpose of the work is a comparative fora analysis of medicinal plants to identify the most prospective plant and further production of a remedy for the avoidance, treatment, and rehabilitation of COVID-19.

Materials and Methodology
Te methodology of this work is based on the recent literature review on the action of biologically active substances in plants, their chemical composition and pharmacognostic properties, and their efect on coronavirus infection ( Figure 1). Data were searched by analyzing the literature in online databases: Web of Science, Scopus, Google Scholar, and PubMed, including ofcial WHO media sites. Te experience of traditional medicine in treating coronavirus infection with plant-based preparations was also critically analyzed, looking for scientifc confrmation in scientifc publications of the efectiveness of the proposed medicinal plants and their preparations.

Result and Discussion
Coronaviruses (Coronaviridae) belong to the family of RNAcontaining viruses capable of infecting humans and some animals and are included in pathogenicity group 2 along with other members of this virus family [7].
Te main route of transmission is direct or indirect exposure to the respiratory tract. Te cause of virus can infect other people, including during the incubation stage of the infection. Te virus is transferred by airborne, open, and contact routes. Factors of transmission are air, that is to say, being in closed and poorly ventilated rooms, food, as well as contaminated objects and surfaces. Te incubation period averages from 2 to 14 days [8].
Te infectious process goes on in several stages. Te initial stage requires viral reproduction, led by mild symptoms and activation of the inherent resistant response.
Adaptive protection is turned on, and either the infection is passed, the virus clears up, or it becomes acute or chronic. Te clinical range can difer depending on the viral load and the immune position of the patient [9]. Patients with chronic diseases, hypertensive patients, diabetics, and the elderly with comorbidities are at risk for developing acute coronavirus [10,11].
COVID-19 disease afects various parts of the human body, producing serious illnesses. Table 1 details the efects of the virus on the internal organs: the heart, lungs, vessels, kidneys, brain, central nervous system, and skin of people.
We would especially like to focus on the Delta strain (Delta COVID-19 (B.1.617.2 or AY.1)). It was early described in India in October 2020, and afterward, the strain was again found in other countries [31]. Te WHO considers the Delta strain to be the most dangerous compared with the common coronavirus [32]. Te mutated strain of coronavirus causes slightly diferent symptoms in infected people than the original coronavirus. Symptoms typical of SARS-CoV-2 such as loss of smell and taste are not observed. Te following symptoms are distinguished: headache, rhinitis, sore throat, fever, and cough [33]. Transmission occurs in different age groups, has a high rate of spread, the incubation period is much shorter, ranging from 1 to 3 days, and an increased viral load is noted [30].
Te Delta strain raises concerns among doctors and scientists because it binds more easily to lung cell receptors and also resists monoclonal antibodies designed to treat the disease [34]. An important feature of the Delta strain is that it can cause mucormycosis and aspergillosis, invasive fungal infections caused by fungi Aspergillus fumigatus, and Rhizopus arrhizus [35]. Fungal infections afect the central nervous system, eyes, joints, and other organs and develop as a result of antibiotics, corticosteroids, and prolonged artifcial ventilation [36].
Since ancient times, medicinal herbs have been used to incur diferent illnesses [37]. It required special plants to provide infections and viruses such as colds and fu, to strengthen the human immune system because the active substances of these plants have a signifcant therapeutic efect. Moreover, chemicals isolated from plants, such as aspirin (from willow bark) and morphine (from opium), are used to produce various medicines. Diseases such as diabetes, hypertension, arthritis, and oncology are treated with medicinal plants [38][39][40].
Moreover, medicinal plants have an antiviral efect and increase the body's resistance to epidemic diseases, which is very relevant at present [41]. Te action of medicinal plants has already shown promising results in studies as an efective treatment to treat severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) [42]. In addition, the combination of traditional and folk medicine methods has reduced the adverse efects of glucocorticoids, antibiotics, and antiviral drugs in the cure of SARS [43]. Medicinal plants can be an efective weapon for treating coronavirus; however, appropriate clinical trials are recommended.
Analysis of the fora of medicinal plants showed the following plants to treat coronavirus infection ( Table 2).

Glycyrrhiza glabra, Glycyrrhiza uralensis (Licorice).
In medicine, licorice is used as an expectorant, cough suppressant, laxative, cardiovascular, respiratory, immunological, anti-infammatory, analgesic, and antipyretic [48]. Glycyrrhiza glabra contains more than 20 triterpenoids and about 300 favonoids, among them glycyrrhizin, a saponin compound isolated from the roots [82]. Several types of research have demonstrated that glycyrrhizin has shown a signifcant inhibitory efect on the infuenza virus and is an efective antiviral compound against the hepatitis C virus (HCV) [83]. A clinical trial conducted in 2003 showed the potential antiviral activity of glycyrrhizin against 2 clinical isolates of coronavirus infection (FFM-1 and FFM-2) from patients [84]. An in vitro research by Shahrajabian et al. demonstrated an antiviral efect; glycyrrhizin suppressed the virus associated with SARS and has been proposed to treat SARS [85].

Artemisia annua L.
Te main bioactive compound of Artemisia is Artemisinin a sesquiterpene lactone having a special peroxide bridge which is separated from wormwood and is used as a remedy against malaria [86]. Artemisinin and its synthetic derivatives have demonstrated signifcant efects against other parasitic diseases [87], several diferent types of cancer [88]

Artemisia vulgaris.
Artemisia contains secondary metabolites such as favonoids, terpenoids, saponins, and polysaccharides [92]. Arglabin, a sesquiterpene lactone located mainly in all wormwood species, shows a marked anticancer efect against diferent tumor cell lines [53]. A lot of analogs, such as artesunic acid, artelic acid, and artemether, can be produced and are sufcient against multidrug-resistant malaria [93]. Artemisia has found several therapeutic uses in folk medicine that are related to the gastrointestinal tract, such as ulcers, indigestion, and liver problems [94]. Te plant is also used to treat worm infestation, anxiety, epilepsy, vegetative neurosis, insomnia, neurasthenia, and general irritability. Te plant essential oil is expected to have a sort of pharmacological activity, with an increased range of bioactivity, because of the metabolites' action of auxiliary chemical components that lead to their functioning through diferent modes of action [95]. Leaf powder or paste is applied to provide skin illnesses and has analgesic efects [52].
3.5. Colchicum autumnale. Colchicum autumnale contains colchicine is an alkaloid and is one of the best-known natural products appealing to a class of organic compounds found as tropines. Te therapeutic properties of colchicine have been identifed for a long time; it is used to treat gout but has attracted increased attention because of its activity as an antimitotic agent [96]. New therapeutic uses of colchicine, in addition to the treatment of gout, are currently being explored. Scientists Schlesinger et al. conducted ten clinical trials of colchicine to deal with SARS-CoV-2 disease [97]. According to the results of the studies, data on its antiinfammatory and antiviral properties were published, the mechanism of activity of colchicine through the tubulincolchicine complex was described, and the process of colchicine action in the fght against COVID-19 was explained [54].

Inula helenium. Preparations from the rhizomes of
Inula helenium have expectorant and anti-infammatory efects, improve appetite, reduce intestinal peristalsis, and reduce the secretion of gastric juice. It is believed that the main biologically active substance of elecampane is alantolactone and related terpenoids. Te rhizomes and roots are used to produce the drug allanthone, which is used to treat gastric and duodenal ulcers. According to Gierlikowska et al., the use of elecampane to treat infammatory respiratory illnesses (e.g., cough, fever, bronchitis, rhinitis, and fu) [56] was confrmed [57].

Aloe vera.
It is one of the most researched and used medicinal plants all over the world, and its pharmacological properties are known. In traditional medicine, the useful properties of aloe are used as a laxative; it increases the peristalsis of the colon in small doses, improves digestion, and increases appetite [58]. Aloe vera ethanol extract (AVE) has been described to have considerable action against the infuenza virus [98]. Aloe vera consists of several individual compounds contained in the antiviral activity: quercetin, catechin hydrate, kaempferol, acemannan, azidothymidine, acyclovir, aloin, emodin [99]. Emodin has antiviral activity against some types of viruses such as human cytomegalovirus, herpes simplex virus type 1, and poliovirus [100]. Aloe vera contains minerals including Ca, Mg, Na, K, Fe, Co, and Zn. Tere is evidence that Zn 2+ inhibits coronavirus RNA and polymerase action in vitro, and zinc ionophores stop the reproduction of these viruses in cell culture [101]. thrombophlebitis. Te presence of salicylates explains the anti-infammatory activity, so an infusion of Filipendula fowers is used as an astringent for the treatment of stomach disorders. Preparations from the rhizome of Filipendula are used to treat various skin diseases, to wash purulent wounds, ulcers, furuncles, and boils [102], in the treatment of oral diseases, with eczema of extremities, trophic ulcers, hemorrhoids, itchy dermatoses, bedsores, scabs, diaper rash [103]. Infusion of stem tops with leaves and fowers of Filipendula is used for gout, rheumatism, stomach pain, as a diuretic, as a diaphoretic, for heart disease, choking, headache, diarrhea, for dysentery, for hysterical convulsions, pain in the stomach, and intestines, in the chest, in the throat [59,60]. It has been experimentally established that medications of Filipendula reduce blood pressure by 40% within 20 minutes [104]. Te fowers and herbs of Filipendula are used in diseases of the upper respiratory tract, as a diaphoretic, in bronchial asthma, and as an antispasmodic agent. Tey have a sedative efect, and they are prescribed for hypertension, epilepsy, neurasthenia, hypochondria, and other neuroses, such as sleeping pills [61][62][63][64][65]. Data on the chemical composition of Chamaenerion angustifolium Seg., indicate its high content of antioxidants and other biologically active substances that cause its therapeutic properties. Te absence of cafeine in it expands the scope of its application to a wide range of age groups, including patients with hypertension, because the cafeine helps narrow blood vessels and reduce the risk of thrombosis. Te above data confrm the high nutritional value of Chamaenerion angustifolium Seg. Tus, tannins, the content of which in Chamaenerion angustifolium Seg. is up to 20%, are represented by tannin, which has an anti-infammatory efect. Tis efect is especially valuable for people with gastrointestinal diseases [67].

Chamaenerion angustifolium
Equally important is the property of tannin to bind and remove toxic metals from the body. Chamaenerion angustifolium Seg. contains a lot of quercetin as well as kaempferol. Tese substances strengthen blood vessels, preventing them from becoming brittle. Tey also protect cells from oxidative stress, thus preventing the body from aging prematurely and getting cancer. Kaškonienė et al. identifed about 50 diferent compounds in the essential oil of Chamaenerion angustifolium Seg. [106,107].
Among vitamins, the above-ground part of Chamaenerion angustifolium Seg. is especially rich in vitamin C. Its content is three times higher than in citrus fruits. Tis vitamin is especially important for preventing aging and cancer processes, as well as improving the absorption of iron and strengthening the walls of blood vessels [108].
Group B vitamins in Chamaenerion angustifolium Seg. are represented by thiamine, nicotinic acid and folic acid. Tese vitamins are known to be anti-stress, normalize digestion, improve brain cell function, and optimize protein and fat metabolism. Leaves and fowers of Chamaenerion angustifolium Seg. contain sufcient amounts of iron (23 mg per 100 g of raw materials), which is essential for human blood hemoglobin, the synthesis of immune system cells, and the digestive and nervous systems. Te high content of manganese (16 mg) and copper prevents the development of anemia, has a benefcial efect on the spleen and liver, supports bone structure, improves memory, and supports growth processes [109].
Depending on the studies that were carried out by the scientists Adamczak et al. [68], traditional uses of Chamaenerion angustifolium Seg. in phytotherapy include insomnia, headaches, tremors, anemia, infections, delirium, and colds [111]. Chamaenerion angustifolium Seg. is required as an antiphlogistic and antiseptic agent to treat mycoses, ulcers, skin rashes, minor burns, wounds, and infammation of ENT diseases [36,69]. Te aerial parts of Chamaenerion angustifolium Seg. (herb and leaves) are used to treat the disorders of stomach and prostate infammation, as well as the liver. Tey also are used for kidney and urinary tract diseases. In general therapeutic practice, Chamaenerion angustifolium Seg. has anti-infammatory, antiproliferative, immunomodulatory, antimicrobial, and antioxidant efects [68]. It is also used to care for wounds and various skin and mucous membrane disorders [112].
As Kadam et al. report, the use of Chamaenerion angustifolium Seg. extracts before infuenza virus disease decreased mortality and extended mean survival time [113]. Tese efects were even more striking when the virus appeared seven days after the last administration of the extract. Extracts of the plant also exhibit antitumor properties, including inhibition of human prostate epithelial cells by PZ-HPV-7 [114,115].
Lasinskas et al. conducted research to evaluate the chemical composition, antioxidant and antibacterial activity 6 International Journal of Biomaterials Group B vitamins, iron It has a pronounced hematopoietic efect, improves blood quality, and increases the level of saturation   International Journal of Biomaterials of ethanol-water extracts (EVE) of Chamaenerion angustifolium Seg. as a valuable source of bioactive substances with antioxidant and antimicrobial characteristic, as well as in vitro evaluation of penetration into human skin of certain EVE compounds and their accumulation in the skin [116]. Te study made it possible to assess the extent to which the active substances of the plant can be useful in protecting not only the skin surface and its deep layers but also the surrounding tissues from oxidative stress and bacterial infection. According to the study, the pharmacological activity of Chamaenerion angustifolium Seg. is due to the content of several biologically active compounds such as phenolic acids, including benzoic acid derivatives such as GA, 3,4-DHB, 4-HB, and cinnamic acid derivatives such as CA [117]. Phenol acids and other antioxidants are considered valuable therapeutic ingredients with antioxidant and antimicrobial properties in topical preparations [13,118]. When using the herb Chamaenerion angustifolium Seg., contraindications and other signifcant side efects have not been identifed. As with any herb, in rare cases, individual intolerance is possible. Also, prolonged use may cause minor gastrointestinal disturbances, passing immediately after stopping it.
Te unique biochemical composition determines the variety of medicinal properties of Chamaenerion angustifolium Seg. Table 3 presents a comparison of the main symptoms of COVID-19 and the medicinal properties of Chamaenerion angustifolium Seg. contributing to their elimination.
To identify the medicinal plant most suitable to treat coronavirus, a comparative study among nine medicinal plants was performed. Te data are demonstrated in Table 4.
According to a comparative analysis, Chamaenerion angustifolium Seg. has the greatest pharmacological efect compared with other types of medicinal plants.
Te high pharmacological activity of Chamaenerion angustifolium Seg. and a wide range of its pharmacological action, along with excellent taste and aromatic properties, are the reason for its demand in the market of herbal medicines. Te modern market price of fermented Chamaenerion angustifolium Seg. is 19 thousand tenge/kg, which at a yield of 4.3-12.4 cwt/ha allows for an average income of 15865 thousand tenges per hectare. One picker manually collects 20-25 kg of leaves per day, which in terms of dry weight is 4-5 kg. A 1-hectare average yield of 8.35 c/h requires 36 man-days of work to collect plant raw materials. Te limitation of the leaves harvesting season to a period of two weeks from the beginning of budding to full fowering provides 3 jobs per hectare per season.
Te technological process of production of fermented Chamaenerion angustifolium Seg. from leaves of Chamaenerion angustifolium Seg. includes collection, drying, twisting, fermentation, drying in an oven, and air drying.
Taking into account the simplicity of the technological process of harvesting and processing, including fermentation, the Chamaenerion angustifolium Seg. is a promising medicinal plant for wide implementation into production and cultivation in rural areas. Tis will create jobs and seasonal income for the local population and provide the pharmaceutical market with efective herbal medicine to alleviate the symptomatic course of COVID-19.

Conclusions
According to the results of comparative analysis of the fora of medicinal plants among plants with antiviral efects, Chamaenerion angustifolium Seg. is the most suitable for the treatment of COVID-19.
From the review of literary sources, it follows that Chamaenerion angustifolium Seg. is a medicinal plant raw material with a high potential for biological activity, which should be used in pharmacy as it possesses all medicinal properties for the cure and rehabilitation of patients with coronavirus. Given the wide range of medicinal properties of Chamaenerion angustifolium Seg., it is necessary to further research in scientifc experiments and implementation in the treatment protocols against the virus.
In conditions of shortage of medicines, it is necessary to introduce in the development of wider use of Chamaenerion angustifolium Seg. Additional economic advantages are the prevalence of the plant in the region (eliminates the cost of transportation), unpretentiousness (does not require special care during cultivation), not require special processing (all parts of the plant are used) does not require extraction of pharmacologically active substances in the production of drugs. Te possibility of using Chamaenerion angustifolium Seg. will create new jobs and give an impetus to the economic development of the region.
A lot of studies are devoted to the potential efect of medicinal plants and herbal preparations on the treatment and prevention of COVID-19 [122][123][124]. For example, the research of Sankar et al. reported the presence of potent phytocompounds in the composition of some medicinal plants. Te study showed that the identifed phytocompounds could be considered promising medicinal compounds [125]. Shree et al. attempted to recognize natural phytochemicals from medicinal plants to use against COVID-19 using molecular docking and molecular dynamics studies. Based on their fndings, they suggest that active phytochemicals from medicinal plants might inhibit Mpro SARS-CoV-2 [126]. Hu et al., in their research, revealed that the citrus favonoid rutin could afect the assembly of viral functional proteins and suppress infammation in the host [127].
Te data presented above clarify that it may recommend medicinal plants and their biologically active substances for use as complementary and alternative medicine or may be potential sources for the discovery and development of drugs against COVID-19, as well as other viral infections.
However, complementary and alternative medicine is often undervalued by the medical system. But for many people, complementary herbal remedies and medicines are the main source of medical care, and sometimes the only one, because of their territorial and fnancial accessibility. In addition, because of the COVID-19 pandemic, the afordability of most herbal remedies makes them more attractive than classic medicines. Undoubtedly, remedies of herbal origin require research, the main difculty in studying them International Journal of Biomaterials is and remains a large list of studies. A more extensive study of Chamaenerion angustifolium Seg. and other medicinal plants requires the study of their biological and pharmacological properties, as well as technological features of processing, conducting clinical trials to get high-quality, safe drugs, and working out the best ways of its reception considering the characteristics of patients. At this stage of research, there is a need for cooperation between botanical and medical research institutions. Te pharmacognostic studies that we have conducted need further clinical validation.
Funding limitations and the inability to transfer results to real clinical settings are signifcant limitations for researchers, so there is an urgent need to continue research work to explain the potential use of medicinal plants and herbal medicines for the treatment and prevention of COVID-19.

Conflicts of Interest
Te authors declare that they have no conficts of interest.