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.


Introduction
Viral diseases are responsible for the global morbidity and mortality of human beings [1]. e pandemic COVID-19 is among such viral outbreaks challenging the healthcare systems around the world [2]. 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 [3]. 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 [4]. Because they contain various active components, medicinal plants can be alternatives to prevent and combat COVID-19 [5].
Globally, millions of people rely on medicinal plants not only for their primary healthcare systems but also for income generation and livelihood improvement [23]. Moreover, at least 25% and 50% of the pharmacopeia are derived from plant products and are originated from natural products, respectively [24]. Nowadays, traditional healers from different habitats and geographical locations are showing new candidate combinations for the treatment of viral infections such as SARS-CoV [5].
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][26][27], due to its cultural acceptability, economic affordability, and efficacy against certain types of diseases compared to modern medicine [28]. 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 [29].
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 [30]. 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 [31]. Plant extracts contain a lot of active components, so they have a wide range of activities against microorganisms.
at is, they act on multiple active sites of the pathogen [32]. erefore, a medicinal plant used to treat one viral infection may serve to fight other viral infections. is 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.

Study Design and Setting.
e 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. e 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. e population density in Ethiopia is 115/km 2 (298 people/mi 2 ) [33]. e total land area is 1,104,300 km 2 [34].

Search Strategies.
e 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.

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.

Data Extraction.
All authors contributed to the data extraction protocol preparation and evaluation. e data extraction protocol consists of the scientific, family, and local names, parts used, preparation methods, administration routes, diseases treated, and references.

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.

Medicinal Plants with Antiviral Active Components.
A range of active compounds with potential antiviral agents for future drug development has been identified from plants [77]. 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).
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 [100]. e Ethiopian medicinal plants Acacia abyssinica, Acacia etbaica, and Acacia nigra [5] and Acanthus polystachyus [78] 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 [101]. 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 [5] and Osyris quadripartite [91].
Acanthus polystachyus [78] contained saponins that possess various biological activities, including antiviral action [103]. Ocimum basilicum, Ocimum lamiifolium,   Evidence-Based Complementary and Alternative Medicine 5  Rabies [38] Evidence-Based Complementary and Alternative Medicine 7  Evidence-Based Complementary and Alternative Medicine 9 (i) Root is crushed and pounded, mixed with water; one-third of the tella cup is given to humans (liver problem); Phytolacca dodecandra root is crushed and pounded, mixed with water; one-third of a cup is given to humans (ii) Dried root of Phytolacca dodecandra powder and one-two cups of domestic alcohol (malakia) are taken orally (for rabies) (iii) Chopped root and leaves mixed with honey are given orally (for rabis) (iv) Fresh root of Phytolacca dodecandra is pounded, mixed with water, one arake glass of the solution is given for 7-10 days (for humans) Oral (i) Liver problem (hepatitis), (ii) Rabies [41,42,48,70] 10

Evidence-Based Complementary and Alternative Medicine
Evidence-Based Complementary and Alternative Medicine  12
Lycorine is a compound with broad antiviral activity. It is reported to possess anti-SARS-CoV activity [6]. It is possessed in Ethiopian medicinal plants traditionally used to treat viral infections, for example, in Crinum abyscinicum Hochst. ex A. Rich. [57].

Conclusions
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. erefore, these medicinal plants should be researched for anti-COVID-19 properties.

Data Availability
All related data have been presented within the manuscript. e dataset supporting the conclusions of this article is available from the authors on request.

Conflicts of Interest
e authors declare that they have no conflicts of interest.