Hrev_master The antiviral properties of edible medicinal plants: potential remedies against coronaviruses Takele Taye Desta,1 Kero Jemal,2 Rediet Sitotaw,1 Debissa Lemessa,3 Melesse Maryo,1,4 Alemtshay Teka,5 Tewodros Mulugeta1 1Department of Biology, College of Natural and Computational Science, Kotebe University of Education, Addis Ababa; 2Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa; 3Deparment of Plant Biology and Biodiversity Management, College of Natural and Computational Sciences, Addis Ababa University, Addis Ababa; 4Ethiopian Biodiversity Institute, Addis Ababa; 5Endod and Other Medicinal Plants Research Unit, Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia Abstract SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is an unparalleled challenge for the international community. Subsequently, an extraordinary effort has been made to contain SARS-CoV-2. However, this has been largely limited to behavioral changes and vaccination. To make the containment strategies effective, behavioral changes and vaccination need to be complemented with alternative preven- tion methods and curative treatments. This work reports the antiviral properties of some of the commonly known edible medicinal plants that can be used as poten- tial remedies to suppress coronaviruses. A growing body of evidence substantiates that edible medicinal plants with antiviral prop- erties that have been proven effective against sibling coronaviruses likely contain the spread of SARS-CoV-2, and they may also suppress the fatality of COVID-19 (coronavirus disease 2019). The secondary metabolites found in herbal medicines do not cause pathogens to develop drug resist- ance, which is a common problem in con- ventional medicines. The use of edible medicinal plants is much safer and causes less panic, thereby avoiding the fear associ- ated with the use of herbal medicines. Right dosages and mixtures of edible medicinal plants need to be rigorously investigated to circumvent unanticipated side effects and chronic health risks. Introduction Infections that are caused by pandemic contagions such as coronaviruses are imposing unprecedented challenges to glob- al health.1,2 For example, several coron- aviruses have threatened public health; among these is SARS-CoV (severe acute respiratory syndrome coronavirus 2), which shares a significant portion of its genomic structure and etiology with SARS-CoV-2.3 SARS-CoV-2 is highly infectious,4 howev- er, it is less fatal than SARS-CoV.5 SARS- CoV-2 is rapidly transmitted through coughing, sneezing, respiratory droplets, or aerosols4 and contagiously via infectious secretions.6 Hitherto, there is no effective treatment for COVID-19.4,7 Therefore, the most reli- able containment strategies are behavioral changes8 – such as social distancing, enhancing hygiene, and the use of personal protection equipment. Tremendous efforts have been made to develop vaccines5 and vaccination has commenced. However, vac- cination needs to be supported by comple- mentary preventive, suppressive, or cura- tive treatments. Moreover, based on the epi- demiology of COVID-19, SARS-CoV-2 may not last soon,9 and given the recent bunch of contagions we have faced novel coronaviruses could instantly emerge; therefore, prevention and treatment efforts need to be intensified and supported by alternative and complementary medica- tions. Although the impact of coronaviruses has been significantly decreased, Worldometers data for April 26, 202310 (https://www.worldometers.info/coron- avirus/) shows that there are ~687 million registered cases and ~6.9 million coron- avirus-related deaths. Still, a few new cases of coronavirus are registered daily in the Worldometers database. All-inclusive efforts need to be made to avoid the devas- tating impact of the coronavirus. Among the complementary strategies, the most envi- ronmentally friendly and safer one could be the use of edible medicinal plants. In the history of mankind, plants have been used as key ingredients for nourish- ment. Paleontological evidence shows that the omnivorous modern-day human once in the course of his evolutionary history was herbivorous.11 Consequently, plants make up the largest portion of the diet of modern humans. Accordingly, the digestive system microflora have developed symbiosis to digest and absorb plant-derived com- pounds.12 This has made plants ubiquitously consumed healthy foods. Some of these plants are not exclusively used as food but also as medicine. For example, an extensive list of medicinal plants with antiviral prop- erties of which some are edible was reviewed by Yasmin et al.13 Moreover, a long list of edible medicinal plants was pro- duced in the Traditional Chinese Medicine Systems Pharmacology Database,14-16 the Encyclopedia of Traditional Chinese Medicine,15 and SymMap.16 Several edible medicinal plants have been also used to treat diseases in India.17 Interestingly, Zhang et al.18 have screened Insilco Chinese medicinal plant databases and have pro- posed several traditional medicines (some of them might be edible) that can be used to contain SARS-CoV-2 or to treat COVID- 19. To increase the prudent use of medicinal plants, it is essential to compile relevant lit- erature on the most recent advancements in the treatment of coronaviruses and sibling respiratory syndromes with edible medici- nal plants as well as the ongoing debates regarding the use of conventional medicines versus traditional medicinal plants. Healthcare in Low-resource Settings 2023; volume 11:11205 Takele Taye Desta, Department of Biology, College of Natural and Computational Science, Kotebe University of Education, Addis Ababa, Ethiopia. E-mail: takele_taye@yahoo.com Key words: SARS-CoV-2, COVID-19, edible medicinal plants, the antiviral properties of phytochemicals, docking effect. Conflict of interest: the authors declare no potential conflict of interest, and all authors confirm accuracy. Ethics approval and consent to participate: not applicable. Informed consent: not applicable. Patient consent for publication: not applicable. Received for publication: 24 January 2023. Accepted for publication: 7 June 2023. This work is licensed under a Creative Commons Attribution 4.0 License (by-nc 4.0). ©Copyright: the Author(s), 2023 Licensee PAGEPress, Italy Healthcare in Low-resource Settings 2023; 11:11205 doi:10.4081/hls.2023.11205 Publisher's note: all claims expressed in this article are solely those of the authors and do not necessarily represent those of their affili- ated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guar- anteed or endorsed by the publisher. [page 22] [Healthcare in Low-resource Settings 2023; 11:11205] Non -co mmerc ial us e o nly [Healthcare in Low-resource Settings 2023; 11:11205] [page 23] Materials and Methods While organizing this report, the pur- sued pieces of literature were looked through using Google Scholar, and the key- words “medicinal plants and coronavirus” were used as search items. As a result, the findings that identified medicinal plants that have been widely used for human consump- tion and have been used to treat coron- aviruses and sibling respiratory syndromes were discussed in this report. Results and Discussions The unique importance of medicinal plants Interestingly, medicinal plants have been validated and used for a long time to produce several drugs with potent antiviral properties.19 Traditionally, plant substances have been used as medicine for more than 5000 years.20 This shows that there is an enriching pool of traditional knowledge and wisdom aligned with the utilization of medicinal plants. Several studies have been conducted on the pharmacological proper- ties of herbal medicines; however, the num- ber of good quality clinical studies is limit- ed (see for instance the review by Eng et al.21 and the references listed in Supplementary Table 1),22-44 which con- strains the broader use of edible medicinal plants. However, Chinese and Koreans have developed guidelines for traditional medi- cines, for example, to treat COVID-19.7 Medicinal plants possess several natural compounds with phytomedicinal properties, subsequently, they are usually broad-spec- trum.9,17 Therefore, they can be used to treat coinfections9 and comorbidities that aggra- vate the fatality of the disease in question. Since the bioactive compounds of medici- nal plants are readily absorbable, they can be used to prevent several infections affect- ing different parts of the body and related physiological functions. Edible medicinal plants are safe to use Besides affordability and being ubiqui- tous and highly diverse, edible medicinal plants with reasonable assumptions may not have side effects or long-lasting health risks, provided that the right dose and appropriate pharmacological procedures are adopted.45 Edible medicinal plants could be wild and/or semi-domesticated types, com- monly or rarely consumed. Since edible medicinal plants are part of our daily meals,2,17 their basic characteristics are widely known by the general populace, which may then help to reduce the adverse impact of unforeseen effects. Therefore, the use of edible medicinal plants lowers the fear and skepticism prevailing against herbal medicines. Interestingly, medicinal plants are less susceptible to drug resistance usually devel- oped by pathogens that are repeatedly exposed to a conventional drug17, and when there is inappropriate (indiscriminate), irregular, and irrational (improper) use of antibiotics.46,47 Medicinal plants have a lot of secondary metabolites and phytochemi- cals, and these substances provide medici- nal plants with several therapeutic roles.47 The activity of secondary metabolites (either in the intermediate or end-product form) found in the crude extracts of medic- inal plants suppresses the development of drug resistance in the microbes.46 This spe- cial attribute of medicinal plants and the side effect of using synthetic drugs may have conferred medicinal plants with broad- spectrum uses. Medicinal plants are readily biodegrad- able; therefore, they do not cause environ- mental pollution. Herbal medicines are widely used16, and their utilization is gain- ing importance.45 For example, 80 percent of the world’s population mainly relies on medicinal plants.48 Interestingly, herbal medicines contain several active substances Review Figure 1. The mode of action of extracts of medicinal plants on viruses causing respiratory syndromes. Medicinal plant extracts can inhibit the invasion of viruses into the animal’s cells, and the infected cells sensitize themselves against the entry of the virus (IFN-pro- duction) (1). Medicinal plant extracts may have viral hemagglutinin or neuraminidase activity (2). Medicinal plant extracts may inhibit the replication of viral RNA (3). Medicinal plant extracts may block the synthesis of viral proteins (4). Medicinal plant extracts may inhibit the spread of the virus in the host (5). Medicinal plant extracts may block the activity of viral proteins and enzymes (6, 7). Medicinal plants' phytochemicals can be extracted using various methods (8). Non -co mmerc ial us e o nly [page 24] [Healthcare in Low-resource Settings 2023; 11:11205] with therapeutic roles.21-44 However, the interaction of these substances may some- times produce undesirable consequences. Therefore, understanding the pharmacolog- ical properties, interactions, side effects, and underlying molecular mechanisms (docking effect) of edible medicinal plants is inevitable to enhance their utilization.21 Bioactive phytochemicals and their antiviral properties Bioactive phytochemicals with anti- microbial properties possessed by edible medicinal plants are used to cure and/or induce/enhance/modulate the immune response.17,49 The preventive and curative capacity of edible medicinal plants inhibits, attenuates, docks, or suppresses the entry and cellular fusion, replication, infectivity, or fatality of the pathogens (Figure 1).50 It is, therefore, vital to understand where and how phytochemicals specifically interact with or interrupt the life cycle of viruses, such as at the point of entry, replication, assembly, or release.45 However, the use of edible medicinal plants largely relies upon the knowledge and wisdom of traditional healers in the less developed world, and it is usually documented using the information retrieved from less rigorous field surveys and has not often been validated by clinical studies.51 This shows that carefully man- aged clinical studies should be carried out to avoid potential risks associated with the use of medicinal plants. 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J Ethnobiol Ethnomedicine 2018;14:1-21. Review Online supplementary materials Table 1. Non -co mmerc ial us e o nly