Candidate Anti-COVID-19 Medicinal Plants from Ethiopia: A Review of Plants Traditionally Used to Treat Viral Diseases
Background. Emerging viral infections are among the major global public health concerns. The pandemic COVID-19 is a contagious respiratory and vascular disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There are no medicines that can treat SARS-CoV-2 except the vaccines. Therefore, searching for plant-originated therapeutics for the treatment of COVID-19 is required. Consequently, reviewing medicinal plants used to treat different viral infections is mandatory. This review article aims to review the ethnobotanical knowledge of medicinal plants traditionally used to treat different viral diseases by the Ethiopian people and suggests those plants as candidates to fight COVID-19. Methods. Articles written in English were searched from online public databases using searching terms like “Traditional Medicine,” “Ethnobotanical study,” “Active components,” “Antiviral activities,” and “Ethiopia.” Ethnobotanical data were analyzed using the Excel statistical software program. Result. From the 46 articles reviewed, a total of 111 plant species were claimed to treat viral infections. Fifty-six (50.4%) of the plant species had reported to have antiviral active components that are promising to treat COVID-19. Lycorine, gingerol shogaol, resveratrol, rhoifolin, oleanolic acid, kaempferol, rosmarinic acid, almond oil, ursolic acid, hederagenin, nigellidine, α-hederin, apigenin, nobiletin, tangeretin, chalcone, hesperidin, epigallocatechin gallate, allicin, diallyl trisulfide, ajoene, aloenin, artemisinin, glucobrassicin, curcumin, piperine, flavonoids, anthraquinone, hydroxychloroquine, and jensenone were some of them. Conclusion. The Ethiopian traditional knowledge applies a lot of medicinal plants to treat different viral infections. Reports of the chemical components of many of them confirm that they can be promising to fight COVID-19.
Viral diseases are responsible for the global morbidity and mortality of human beings . The pandemic COVID-19 is among such viral outbreaks challenging the healthcare systems around the world . From 31 December 2019 to 31 October 2020, this pandemic resulted in 45,667,780 cases and 1,189,499 deaths globally and 95,789 cases and 1,464 deaths in Ethiopia . However, no specific medications and drugs are known to treat this viral disease. Consequently, reports show that people from different countries use medicinal plants for the prevention and treatment of COVID-19, although not confirmed by the World Health Organization (WHO) for safety issues . Because they contain various active components, medicinal plants can be alternatives to prevent and combat COVID-19 .
Plant secondary metabolites like lycorine , gingerol shogaol , resveratrol rhoifolin , oleanolic acid , kaempferol , rosmarinic acid , almond oil , ursolic acid , hederagenin, nigellidine, and α-hederin [11, 13], apigenin, ethyl cholate, nobiletin, tangeretin, chalcone, and hesperidin [10, 14, 15], epigallocatechin gallate , allicin, diallyl trisulfide ajoene, and apigenin [14, 17], aloenin , artemisinin [6, 19], glucobrassicin [10, 11], apigenin , curcumin , piperine , flavonoids, anthraquinone, and hydroxychloroquine , and jensenone  are reported to have antiviral activities. The mechanism of action of these secondary metabolites may be due to their greater binding affinity for SARS-CoV-2 6LU7 and 6Y2E proteases and inhibition of SARS-CoV-2 M protease (Mpro) and Spike (S) glycoprotein [6–22].
Globally, millions of people rely on medicinal plants not only for their primary healthcare systems but also for income generation and livelihood improvement . Moreover, at least 25% and 50% of the pharmacopeia are derived from plant products and are originated from natural products, respectively . Nowadays, traditional healers from different habitats and geographical locations are showing new candidate combinations for the treatment of viral infections such as SARS-CoV .
Using traditional medicine has a long history in Ethiopia. About 80% of the Ethiopian population is still dependent on the use of folk medicine [25–27], due to its cultural acceptability, economic affordability, and efficacy against certain types of diseases compared to modern medicine . However, the plants and the associated indigenous knowledge in the country are gradually declining because of environmental degradation, deforestation, lack of documentation, and potential acculturation .
Common cold, influenza, and COVID-19 share common characteristics. All of them affect the respiratory tract and have modes of transmission: direct contact, droplets, and fomites. Cough, sneezes, fever, shortness of breath, sore throat, and headache are among the common symptoms of these diseases . Traditional healers from Ethiopia use medicines of plant origin to treat viral infections like the common cold, rabies, influenza, herpes simplex, herpes zoster, and hepatitis. Due to their fewer side effects, better patient tolerance, and relatively low cost, the use of medicinal plants is a common practice by the Ethiopian people.
Due to its ecological and cultural diversity, Ethiopia is a rich source of herbal medicine . Plant extracts contain a lot of active components, so they have a wide range of activities against microorganisms. That is, they act on multiple active sites of the pathogen . Therefore, a medicinal plant used to treat one viral infection may serve to fight other viral infections. This review, therefore, focuses on the identification of medicinal plants used by traditional healers of Ethiopia to treat viral diseases and extrapolates this knowledge for the fight of COVID-19.
2.1. Study Design and Setting
The location of Ethiopia is in the horn of Africa. Its boundaries are Eritrea to the North, Djibouti and Somalia to the East, Sudan and South Sudan to the West, and Kenya to the South. The current UN report shows that the Ethiopian population is estimated to be 115,855,859. Ethiopia’s population is equivalent to 1.47% of the world’s population. Around 21.3% of the population is an urban community. The population density in Ethiopia is 115/km2 (298 people/mi2) .The total land area is 1,104,300 km2 .
2.2. Search Strategies
The authors explored articles from PubMed, ScienceDirect, and Web of Science search engines using the following core search terms and phrases: “Traditional Medicine,” “Ethnobotanical study,” “Active components,” “Antiviral activities,” and “Ethiopia.” We used the search terms separately and in combination with Boolean operators like “OR” or “AND.” Besides, we searched for gray literature through the review of available references. Searching for relevant literature included in this systematic review was conducted from September 2020 to October 2020.
2.3. Inclusion and Exclusion Criteria
Studies that were written in the English language, reporting about the antiviral activity of traditional medicines, phytochemical analysis of medicinal plants, and candidate anti-COVID-19 medicinal plants in Ethiopia, Africa, China, Europe, and Western countries, were retrieved and included in this study. However, we excluded studies that did not contain antiviral medicinal plants.
2.4. Data Extraction
All authors contributed to the data extraction protocol preparation and evaluation. The data extraction protocol consists of the scientific, family, and local names, parts used, preparation methods, administration routes, diseases treated, and references.
2.5. Data Analysis
Ethnobotanical data were entered in an Excel spreadsheet and analyzed using Excel statistical software program. We tabulated and compiled quantitative data using descriptive statistics to identify the number and percentage of species and families of antiviral plants and expressed them in tables.
3. Results and Discussion
3.1. Search Results
From the total of 260 articles retrieved, only 46 (17.7%) of the studies met the eligibility criteria (Figure 1).
3.2. Identified Plants with Antiviral Activities
From the 46 articles reviewed, 111 plant species claimed to treat eleven viral infections. The most frequently reported viral diseases to be treated by the 111 plants were rabies (reported 36 times), hepatitis (30 times), common cold (26 times), herpes zoster (17 times), influenza (10 times), Herpes simplex virus (8 times), Wart (6 times), HIV-1 (5 times), Bursal viral diseases (once), flu (once), and Smallpox (once) (Table 1).
3.3. Taxonomic Diversity of Medicinal Plants Used for the Treatment of Viral Diseases in Ethiopia
We reviewed 162 plants which were grouped under 111 species and 57 families (Table 2). Among the families, Fabaceae was represented by 8 (7.2%) species, Solanaceae and Lamiaceae by 6 (5.4%) species each, Euphorbiaceae and Asteraceae by 5 (4.5%) species each, and Meliaceae, Vitaceae, Apiaceae, Anacardiaceae, Moraceae, Oleaceae, Cucurbitaceae, Rutaceae, and Acanthaceae by 3 (2.73%) species each, and the remaining 43 families were represented by 1 to 2 species (Table 2).
Solanaceae was represented by n = 12, 7.41% plants, followed by Euphorbiaceae (by n = 11, 6.8% plants), Fabaceae and Lamiaceae (by n = 9, 5.6% plants each), Alliaceae and Phytolaccaceae (by n = 8, 4.9% plants each), Acanthaceae (by n = 7, 4.3% plants), Myrtaceae and Zingiberaceae (by n = 6, 3.7% plants each), Asteraceae and Moraceae (by n = 5, 3.09% plants each), and the remaining 43 families by 1 to 4 plants (Table 2).
3.4. Medicinal Plants with Antiviral Active Components
A range of active compounds with potential antiviral agents for future drug development has been identified from plants . People in Ethiopia use different medicinal plants to treat different viral infections even without knowing their active components (Table 1). However, different literature shows that 56 (50.4%) of the plants reviewed contained components with antiviral activity (Table 3).
Flavonoids are secondary metabolites with antiviral properties . The Ethiopian medicinal plants Acacia abyssinica, Acacia etbaica, and Acacia nigra , Moringa borziana , Acanthus polystachyus , Azadirachta indica , and Osyris quadripartite  were reported to contain flavonoids.
Reports show that tannins block virus attachment, entry, and cell-to-cell spread by binding to viral glycoproteins on viruses and the surfaces of infected cells . The Ethiopian medicinal plants Acacia abyssinica, Acacia etbaica, and Acacia nigra  and Acanthus polystachyus  are reported to have tannins so that they can be good candidates to fight COVID-19.
Many terpenoids of plant origin have antiviral activities against severe acute respiratory syndrome coronavirus . Medicinal plants reviewed in the present study may possess terpenoids. Studies among some of these medicinal plants show that they possess these secondary metabolites. Some of the medicinal plants with terpenoid active components were Acacia abyssinica, Acacia etbaica, and Acacia nigra  and Osyris quadripartite .
Polyphenols have demonstrated potent antiviral activities. For example, the polyphenol in green tea controls viruses such as hepatitis C, chikungunya, hepatitis B, herpes simplex virus type 1, influenza A, vaccinia, adenovirus, reovirus, vesicular stomatitis, and Zika (ZIKV) . Acacia abyssinica, Acacia etbaica, and Acacia nigra , Acanthus polystachyus , and Azadirachta indica  of the present review contained polyphenols in their extracts.
Acanthus polystachyus  contained saponins that possess various biological activities, including antiviral action . Ocimum basilicum, Ocimum lamiifolium, Ocimum urticifolium, and Olea europaea subsp. cuspidate , Osyris quadripartite , and Acokanthera schimperi  contain ursolic acid which is a pentacyclic triterpenoid with potent antiviral activities .
Another plant secondary metabolite with antiviral activity is oleanolic acid . It is reported from Syzygium aromaticum , Ocimum basilicum, Ocimum lamiifolium, Ocimum urticifolium, and Olea europea subsp cuspidate , Osyris quadripartite , Acokanthera schimperi , Dregea schimperi , Euphorbia abyssinica , and Phytolacca dodecandra . Oleanolic acid has a binding affinity for SARS-CoV-2 M protease and Spike (S) glycoprotein .
The plant metabolite quercetin inhibits viral entry into target cells via interaction with viral HA protein . Medicinal plants from Ethiopia, Allium cepa , Lepidium sativum , Azadirachta indica , Osyris quadripartite , Amaranthus hybridus Linn , Clematis hirsute , Carissa edulis , Ricinus communis , and Ruta chalepensis , are reported to contain quercetin.
Epigallocatechin-3-O-gallate (EGCG) is known to inhibit a variety of DNA and RNA viruses . It is found in Camellia sinensis  and Allium cepa . Allicin exhibits antiviral, antifungal, and antiparasitic activities . This phytochemical is reported from Allium sativum [14, 17], a medicinal plant used to treat viral infections by people in Ethiopia.
In vitro and in vivo results show that apigenin exhibits antiviral activities . It is found in Capsicum annuum , Citrus aurantium [5, 10, 14, 15], Citrus limon [5, 10, 14, 15], and Allium cepa [14, 17]. Reports show that kaempferol has antiviral activities against influenza A virus (H1N1 and H9N2), human immunodeficiency virus (HIV) 1, and JEV . Many medicinal plants used to treat viral infections in Ethiopia such as Citrus aurantium L., Citrus limon (L.) Burm. f., Capsicum annuum L., Eucalyptus globulus, Osyris quadripartite, Amaranthus hybridus Linn., Clematis hirsute, Ricinus communis L., Ruta chalepensis L., Carissa edulis, Phaseolus vulgaris also contain this active component [10, 11, 13, 22, 80, 83, 84, 91, 92, 95].
Lycorine is a compound with broad antiviral activity. It is reported to possess anti-SARS-CoV activity . It is possessed in Ethiopian medicinal plants traditionally used to treat viral infections, for example, in Crinum abyscinicum Hochst. ex A. Rich. .
Traditional healers in Ethiopia have knowledge of medicinal plants with potential antiviral activity. Literature shows that the majority of the plants prescribed by traditional healers in Ethiopia have antiviral compounds. Therefore, these medicinal plants should be researched for anti-COVID-19 properties.
All related data have been presented within the manuscript. The dataset supporting the conclusions of this article is available from the authors on request.
Conflicts of Interest
The authors declare that they have no conflicts of interest.
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