- Open Access
Role of ethno-phytomedicine knowledge in healthcare of COVID-19: advances in traditional phytomedicine perspective
Beni-Suef University Journal of Basic and Applied Sciences volume 11, Article number: 96 (2022)
Since the outbreak of the COVID-19 virus, ethnomedicinal plants have been used in diverse geographical locations for their purported prophylactic and pharmacological effects. Medicinal plants have been relied on by people around the globe for centuries, as 80% of the world’s population rely on herbal medicines for some aspect of their primary health care needs, according to the World Health Organization.
This review portrays advances in traditional phytomedicine by bridging the knowledge of ethno-phytomedicine and COVID-19 healthcare. Ethnomedicinal plants have been used for symptoms related to COVID-19 as antiviral, anti-infective, anti-inflammatory, anti-oxidant, antipyretic, and lung–gut immune boosters. Traditionally used medicinal plants have the ability to inhibit virus entry and viral assembly, bind to spike proteins, membrane proteins, and block viral replications and enzymes. The efficacy of traditional medicinal plants in the terms of COVID-19 management can be evaluated by in vitro, in vivo as well as different in silico techniques (molecular docking, molecular dynamics simulations, machine learning, etc.) which have been applied extensively to the quest and design of effective biotherapeutics rapidly. Other advances in traditional phytomedicines against COVID-19 are controlled clinical trials, and notably the roles in the gut microbiome. Targeting the gut microbiome via medicinal plants as prebiotics is also found to be an alternative and potential strategy in the search for a COVID-19 combat strategy.
Since medicinal plants are the sources of modern biotherapeutics development, it is essential to build collaborations among ethnobotanists, scientists, and technologists toward developing the most efficient and the safest adjuvant therapeutics against the pandemic of the twenty-first century, COVID-19.
COVID-19 is a pandemic disease of the twenty-first century declared by the World Health Organization and caused by a zoonotic virus, known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which created a catastrophe worldwide with its spread in late 2019. SARS-CoV-2 causing COVID-19 disease produces several symptoms in the human body, which are categorized by the World Health Organization under most common symptoms (fever, dry cough, tiredness), less common symptoms (aches and pains, sore throat, diarrhea, conjunctivitis, headache, loss of taste or smell, rash on skin), and serious symptoms (shortness of breath or difficulty breathing, chest pain or pressure, loss of speech or movement).
It is of great interest that the World Health Organization has been supporting research into traditional medicines for COVID-19 in Africa . Beyond their direct use for COVID-19, phytomedicine or medicinal plants are also used as dietary supplements for supportive therapy to improve immunity against viral infections . In Egypt, about 1/3 of 301 adult participants have mentioned using vitamins/zinc and immune-boosting drinks , made from traditionally used medicinal plants to reduce/prevent COVID-19 severity . In China, the USA, and South Asia, the demand for medicinal plants has increased due to the SARS-CoV-2 epidemic , and 91.50% of the Chinese COVID-19 cases have used traditional Chinese medicine that may have resulted significantly in improving symptoms, reducing mortality and reinfection rates . Concomitantly, research into phytomedicines and foods and COVID-19 has exploded.
Yang et al. have demonstrated that plant-based foods as alternative medicine can possess immunomodulatory and antiviral properties for the possible preventive strategy against COVID-19 . In England, East Kent Hospitals researchers are trialing Sambucol Black Elderberry liquid as a treatment for COVID-19 . Plant-based functional foods such as Allium cepa L., Allium sativum L., Curcuma longa L., Camellia sinensis (L.) Kuntze, Glycine max (L.) Merr., Mangifera indica L., and Abelmoschus esculentus (L.) Moench and plant spices such as Cinnamomum cassia (L.) J.Presl, Piper nigrum L., and herbs such as Ocimum basilicum L., and Tinospora cordifolia (Lour.) Merr. have been reported for potential antiviral and immunostimulatory properties against COVID-19 . In a preliminary inventory study, Pieroni et al. have provided a detailed overview of 193 plant species as “foods medicine” that are used in the 17 countries, regions, or cities for COVID-19 healthcare .
KTF (Korean Traditional foods) prepared with edible plants, herbs, and mushrooms have the potential to target ACE2 receptors or may disrupt any step of a virus infection pathway, improve gut–lung immunity, and support strong respiratory immunity, and KTF also have protective and immunomodulatory effects in preclinical and clinical studies, reviewed by Das et al. . Bellik et al.  have reviewed and demonstrated the roles of micronutrients and phytochemicals based on evidence from in vitro studies and controlled clinical trials against COVID-19 symptoms.
Singirikonda et al. identified edible dry fruits and seeds with demonstrated immune stimulation and antiviral efficacy as potential agents against COVID-19. These were seeds of Prunus amygdalus Batsch, fruits of Phoenix dactylifera L., fruits of Juglans nigra L., nuts of Arachis hypogea L., nuts of Corylus avellana L., seeds of Helianthus annuus L., fruits of Carya illinoinensis (Wangenh.) K.Koch, fruits of Castanea sativa Mill., fruits of Pistacia Vera L., nuts of Anacardium occidentale L., seeds of Prunus armeniaca L., fruits of Vitis vinifera L., fruits of Prunus domestica L., fruits of Ficus carica L., nuts of Euryale ferox Salisb., seeds of Linum usitatissimum L., seeds of Salvia hispanica L., seeds of Cucurbita pepo L., nuts of Areca catechu L., and kernel of Cocos nucifera L. . In addition, some medicinal herbs such as the powder of Curcuma longa L., seeds of Trachyspermum ammi (L.) Sprague, peel of Allium sativum L., and resin of Styrax benzoin and Boswellia species can be used as traditional fumigations to disinfect the environment .
For this review, we accumulated and summarized ethnomedicinal plant knowledge reported from the diverse geographical locations in the treatment and prevention of coronavirus disease (COVID-19); the literature search has conducted and collected until the end of June 2022 from the WHO COVID-19 database (https://search.bvsalud.org/global-literature-on-novel-coronavirus-2019-ncov/). Other relevant scientific literature available on Google Scholar, Semantic Scholar, and PubMed as well as the WHO COVID-19 database has been evaluated to perform further associated analysis. The use of traditional medicinal plants in the treatment of COVID-19-associated symptoms and clinical, preclinical, in vitro, in vivo, and in silico antiviral efficacy of traditional phytomedicines against SARS-CoV-2 has been selected for the review. This review aims to portray a bridge between advances in ethno-phytomedicine and COVID-19 healthcare. Further to be noted, the accepted botanical name was confirmed in the World Flora Online (http://www.worldfloraonline.org/) and in NCBI Taxonomy Browser (https://www.ncbi.nlm.nih.gov/taxonomy).
2 Main text
2.1 Ethnomedicine in COVID-19 management from diverse geographical locations
Ethnomedicine is a study of traditional medicine of particular culture that associates ideas and behaviors of how to treat illness and keep healthy . The knowledge of plant-based ethnomedicine or traditional medicine and their derivatives is pivotal for the discovery of new drugs  as well as beneficial to treating or preventing coronavirus disease (COVID-9) and related infectious symptoms . The knowledge of ethnomedicine is usually inherited verbally by people living in a culture . Ethnomedicines include medicinal plants used for the prophylactic or treatment of coronavirus disease notably because of their purported antiviral, anti-pyretic, anti-inflammatory, anti-oxidant, and immunostimulatory activities, as well as respiratory immunity-boosting activities. Bioactive compounds in medicinal plants can also enhance membrane integrity to prevent viral entry by binding to envelope proteins, regulating ion channels, and modulating enzymes . The active binding sites of SARS-CoV-2 that can be potential drug targets are chymotrypsin-like protease, RNA-dependent RNA polymerase, hemagglutinin esterase, papain-like protease, 2′-O-methyltransferase, helicase, spike receptor-binding domain, ACE2 receptor, and glucose-regulated proteins .
Ethno-phytomedicines or traditional medicinal plants are promising for the alternative management of SARS-CoV-2 as they can block and bind to ACE2 receptors, SARS-CoV helicase, and TMPRSS2 as well as inhibit SARS-CoV-2 entry and replication, reviewed by Ugwah-Oguejiofor and Adebisi . Phytochemicals in medicinal plants have also been demonstrated to exhibit several mechanisms against coronaviruses by targeting virus entry inhibition, viral replication enzymes inhibition, and blockage of virus release activity as well as inhibition of SARS-CoV-2 spike protein, PLpro, and 3CLpro [65, 72]. Examples include emodin and baicalin, which can target spike protein, and Iguesterin, Cryptotanshinone, Silvestrol, and Sotetsuflavone, which can target 3CLpro, PLpro, helicase, and RDRP, respectively . Lectins (mannose-specific) can inhibit binding of SARS-CoV-2 to host cell by targeting the glycans of SARS-COV-2 spike glycoprotein . Table 1 lists some potential SARS-CoV-2 inhibitory phytochemicals.
Shoaib and coauthors have summarized various ethnomedicinal plants and their phytochemicals to analyze the potency of COVID-19 treatment and prevention . The plant species Lycoris radiata (L'Hér.) Herb., Artemisia annua L., Pyrrosia lingua (Thunb.) Farw., and Lindera aggregata (Sims) Kosterm. showed the median effective concentration = 2.4–88.2 μg/mL against anti-SARS-CoV . Further noted, medicinal plants are the source of antiviral bioactive compounds against SARS-CoV-2 infections that can be determined by in vivo and in vitro assays . Extracts of two medicinal plants that are used in Colombian traditional medicine, Gliricidia sepium (Jacq.) Walp., and Piper tuberculatum Jacq. showed in vitro anti-SARS-CoV-2 activity .
In another study, Hafez Ghoran and coauthors summarized information on ethnomedicinal plants and demonstrated their phytochemical constituents for the potential discovery of novel therapeutics against COVID-19 . Another review study has reported 93 plant-derived antiviral compounds that are potential for the treatment of COVID-19 . Since the outbreak of SARS-CoV-2, many countries from diverse cultures have shared their knowledge of ethnomedicinal plants for the prospective treatment and prevention of COVID-19, and Table 2 compiles ethnomedicinal plants used against COVID-19 and related symptoms reported from diverse geographical locations.
2.1.1 Asian ethnomedicinal plants in COVID-19 healthcare
In Bangladesh, 15 medicinal plants (see Table 2) are reported in case studies to have been used as traditional home remedies for COVID-19 by people who tested positive for SARS-CoV-2 infection. Preparation of these plant species such as Cinnamomum verum J.Presl, Laurus nobilis L., and Syzygium aromaticum (L.) Merr. & L.M.Perry included being boiled in water and the vapor inhaled; certain edible species were used to prepare tea; and consumed as food, especially sour fruits such as Averrhoa carambola L., Citrus x aurantium L., Citrus limon (L.) Osbeck, and Mangifera indica L. .
As reported in Table 2, in Nepal, a total of 60 plant taxa have been cataloged that were used for the symptoms of COVID-19; whereas, in Thailand was the highest cataloged species with a total of 491 plant species, mainly reported to be used against COVID-19-related symptoms such as fever, cough, diarrhea, skin ash, headache, and muscle pain . Medicinal plants such as Eurycoma longifolia Jack, Coscinium fenestratum (Gaertn.) Colebr., and Eleutherine bulbosa (Mill.) Urb. have been used traditionally for stimulating immunity during the COVID-19 pandemic in Kalimantan, Indonesia .
The Adi community residing in Arunachal Pradesh, India, has reported the traditional uses of 39 plant species against asthma, bronchitis, cough, sinusitis, diabetes, malaria, typhoid, and jaundice in the search for immune-stimulatory agents against COVID-19 . Another study has reviewed a total of 55 ethnomedicinal plants of the Himalayas that were used against bronchitis which is a respiratory tract infection caused by influenza virus, rhinovirus, adenovirus, coronavirus, and respiratory syncytial virus; out of 55 only 6 plants (Hyoscyamus niger L., Justicia adhatoda L., Ocimum basilicum L., Plantago major L., Verbascum Thapsus L., Zingiber officinale Roscoe) have reported in vitro antiviral activity against viruses causing bronchitis .
2.1.2 African ethnomedicinal plants in COVID-19 healthcare
South African traditional medicinal plants have been used for COVID-19 symptoms such as coughs, colds, and fever and have exhibited antiviral activity against coronaviruses or similar viruses . Chikowe and coauthors reviewed and listed 306 Malawi medicinal plants, of which 127 plants have been implicated in management of at least one of the COVID-19-related symptoms or used for against viral infections. Among 127 medicinal plants, Azadirachta indica A.Juss. was the most frequently used traditional medicinal plant against COVID-19-related symptoms followed by Moringa oleifera Lam., Pyrenacantha kaurabassana Baill., and Sclerocarya birrea (A. Rich.) Hochst. .
In Morocco, the most commonly used medicinal plant against COVID-19 was Eucalyptus globulus Labill., which was reported in 3 different studies [25, 32, 44]. Eucalyptus globulus Labill., its essential oils, and active compounds have antiviral effects and anti-infective properties [16, 30]. In addition, the Moroccan people living in different prefectures, are reported to use medicinal plants for the prevention and treatment of COVID-19. A total of 46 medicinal plants were identified, of which 25 species (most cited species: Zingiber officinale Roscoe, Olea europaea L., Vitis vinifera L., and Allium sativum L.) strengthen the immune system, 18 species (most cited species: Eucalyptus globulus Labill., Trigonella foenum-graecum L., and Aloysia triphylla (L'Hér.) Britton) relieve respiratory infection symptoms caused by SARS-CoV-2, and 11 species (most cited species: Eucalyptus globulus Labill., Lavandula dentata L., and Eugenia caryophyllata (L.) Alston) cleanse/sanitize the area . Notably, polyherbal-based hydrotherapy obtained from African indigenous knowledge has been suggested to be used against COVID-19, including other infectious diseases in Nigeria .
As reported in Table 2, in Ethiopia, 32 herbal and non-herbal medicinal products and 15 plant species have been used in African traditional medicine to treat and prevent symptoms of COVID-19 . In another study, a total of 111 plant species have been identified which are used to treat viral infections by the traditional healers of Ethiopia and are suggested as potential therapeutics against COVID-19 . In West Africa, a total of 145 plant species have been identified that have been in use for the management of respiratory tract diseases during the COVID-19 pandemic, wherein Guiera senegalensis J.F.Gmel., Sterculia setigera Delile, Bridelia ferruginea Benth., Euphorbia hirta L., and Terminalia avicennioides Guill. & Perr. were the most cited plants .
In Cameroon, among 29 plant species, Citrus aurantiifolia (Christm.) Swingle, Zingiber officinale Roscoe, and Allium sativum L. were reported as the most commonly used for COVID-19 symptoms . A recent review on Cameroonian traditional medicinal plants published on March 2021 has recorded a total of 230 plant species as the potential sources of COVID-19 therapies. Among these species, 90 have been reported for traditional uses against at least 3 common COVID-19 symptoms, 30 species have been confirmed for having anti-COVID-19 phytochemicals, and 10, 52, and 14 species for immunostimulatory, anti-inflammatory, and antiviral properties, respectively .
2.1.3 South American ethnomedicinal plants in COVID-19 healthcare
Peru has reported a total of 17 plant species that have been in use in the treatment of respiratory symptoms during the COVID-19 pandemic. Among these, the most commonly used plant species were Eucalyptus globulus Labill., Piper aduncum L., Zingiber officinale Roscoe, Allium sativum L., Matricaria recutita L. .
2.1.4 Turkish ethnomedicinal plants in COVID-19 healthcare
In Turkey, a cross-sectional survey study was conducted among 389 participants wherein 153 (39.3%) participants reported to have used traditional and complementary medicine during COVID-19, especially, as herbal medicines and nutritional supplements such as vitamins . Medicinal plants such as Rosa canina L., Mentha × piperita L., Sambucus nigra L., Olea europaea L., Eucalyptus spp., Melissa officinalis L., and Origanum vulgare L. have been used in Turkish folk medicine for centuries to treat flu and have been suggested for potential use in COVID-19 treatment .
2.1.5 Sub-Saharan Africa ethnomedicinal plants in COVID-19 healthcare
A total of 99 plant species have been used as traditional medicines against three common symptoms of COVID-19, such as fatigue, fever, and coughs in 16 sub-Saharan Africa countries. Zingiber officinale Roscoe, Lippia javanica (Burm.f.) Spreng., Ocimum gratissimum L., Citrus limon (L.) Osbeck, and Artemisia afra Jacq. ex Willd. were found to be the most commonly used medicinal plants in several countries of the region .
Overall, from the compilation of the data in Table 2, it has been observed that the most cited plant species (marked bold) that were used against COVID-19 symptoms in diverse geographical locations are a total of 16 plants species which were cited at least two times. All of these plants and their derivatives have possessed antiviral activity validated by in vitro, in vivo, and in silico pharmacological evaluations (see Table 3).
2.2 Traditional aromatherapy and essential oils for COVID-19 healthcare
Essential oils have been used for their pharmacological activities in different traditional medicines worldwide such as Arabian, Ayurvedic, Chinese, Iranian, Korean, American, and European Pharmacopoeias, and essential oils of Eucalyptus, Mentha, and Citrus have been registered for clinical trials . Plant-derived essential oils or volatile oils have antiviral compounds which may aid in the management of COVID-19 symptoms [59, 122]. Essential oils of aromatic plants that have virucidal activity can be a hope for effective anti-COVID-19 therapy development because essential oils have been shown to disrupt the viral membrane proteins. In recent times, the antiviral and virucidal properties of essential oils and their compounds have been reviewed (refer to [85, 120]). Furthermore, Saleem and Ezzat  have discussed and given perspectives on the antiviral activity of some essential oils on COVID-19 aspects. Aromatherapy and compounds in essential oils can also reduce inflammation, irritation, muscle aches, ameliorate headaches, insomnia, and indigestion, and protect the respiratory system, as well .
Carvacrol, a bioactive compound in essential oils that belongs to many aromatic plants, exerts immunomodulatory, anti-inflammatory, and antiviral properties as well as can be potential for COVID-19 therapeutics development . Compounds like anethole, cinnamaldehyde, carvacrol, geraniol, cinnamyl acetate, L-4-terpineol, thymol, and pulegone from essential oils of aromatic plants have the potential to inhibit spike proteins of the virus, assessed by molecular docking and the conceptual density functional theory . Eucalyptol-rich essential oils can be useful remedies for patients with mild infections caused by COVID-19, notably against respiratory infections . The possible mechanisms of essential oils from cinnamon to decrease oxidative stress and inflammation in patients with COVID-19 have been reviewed .
In silico approaches have also been employed to evaluate the potential antiviral efficacy of essential oil compounds against SARS-CoV-2 such as citronellol, alpha-terpineol, eucalyptol, d-limonene, 3-carene, o-cymene, and alpha-pinene found in essential oils of Eucalyptus and Corymbia species , as well as cuminal, carvacrol, myrtanol, and pinocarveol . Essential oil compounds of Brazilian plant species that are used in traditional medicine have shown anti-COVID-19 potential by a molecular docking study, see Table 4 . In addition, two controlled clinical trials have been registered to assess the efficacy of plant-derived essential oils against asymptomatic and symptomatic COVID-19 patients (Trial ID: CTRI/2021/07/034962) in India, and post-COVID-19 fatigue (ClinicalTrials.gov identifier: NCT04980573) in the United States. Above all else, active constituents in essential oils such as phenols, terpenoids, alkaloids, and phenylpropanoids possess potent antiviral properties and are safe for human use with fewer side effects .
2.3 Advances in traditional phytomedicines and their purported prophylactic and pharmacological effects on SARS-CoV-2
2.3.1 Role of ethnomedicinal plants for in silico evaluation against SARS-CoV-2
The antiviral activity of the extracts of medicinal plants and their bioactive compounds have been confirmed by in vitro, in vivo, and in silico assays to inhibit direct entry of the SARS-CoV-2 and ACE2 receptors as well as block the serine protease TMPRRS2. It is also reported that medicinal plants can inhibit papain-like or chymotrypsin-like proteases that are required in the life cycle of SARS-CoV-2 [4, 24]. Several plant biometabolites including extracts have been reported previously for in vivo and in vitro anti-coronavirus properties such as lectins, saikosaponins, emodin, quercetin derivatives, lectin, ethanolic, and water extract of the plant parts or whole plant . Traditional medicinal plants and their secondary metabolites have been evaluated by an in silico approach against coronavirus for the inhibition of hACE2 receptor that facilitates virus entry into host cells, also studied for inhibition of non-structural proteins 3CLpro and PLpro .
Molecular docking was conducted to investigate compounds of selected South African traditional medicinal plants and their potential inhibitory activities against SARS-CoV-2 RDRP, 3CLpro, and SARS-CoV-2 RBD. Among those investigated were arabic acid, which was isolated from Acacia senegal (L.) Willd.; and L-canavanine from Sutherlandia frutescens (L.) R.Br., reported for inhibition of SARS-CoV-2 3C-like main protease; and hypoxoside from Hypoxis hemerocallidea Fisch., C.A.Mey. & Avé-Lall. and uzarin from Xysmalobium undulatum (L.) W.T.Aiton, which were reported for inhibition of SARS-CoV-2 RBD and SARS-CoV-2 RNA-dependent polymerase . In addition, Attah and colleagues reviewed evidence-based antiviral and anti-SARS-CoV-2 properties of African traditional medicinal plants on the basis of in silico, in vitro, and in vivo approaches .
Phytochemicals of 3 Indian traditional medicinal plants, Mentha arvensis L., Coriandrum sativum L., and Ocimum sanctum L., were found to exhibit in silico high binding affinity to the nucleocapsid phosphoprotein (N) of SARS-CoV-2, which has a key role in replication, transcription, and viral genome assembly . A molecular docking analysis conducted by Khan and coauthors to evaluate anti-SARS-CoV-2 activity showed that EGCG (epigallocatechin gallate) exhibits very strong interactions through binding energies of − 9.30, − 8.66, and − 8.38, kcal/mole with the free enzyme of main protease ( 6Y2E), chimeric receptor-binding domain complexed with human ACE2 ( 6VW1), and NSP15 endoribonuclease ( 6VWW) encoded proteins of SARS-CoV-2, respectively . In a literature review study, an Angelica keiskei (Miq.) Koidz-derived bioactive compound, xanthoangelol E, showed strong inhibitory activity with IC50 value of 1.2 μM against SARS-CoV PLpro, and also quercetin was indicated as being a promising antiviral bioactive compound . Bioactive compounds of medicinal plants of Indian origin such as Cucurbitacin E and orientin can be promising candidates for the development of COVID-19 therapeutics, investigated against the structural targets of SARS-CoV-2 (Mpro and spike protein) and human ACE2 receptor .
Phytoconstituents of Withania somnifera (L.) Dunal, Tinospora cordifolia (Willd.) Miers, and Asparagus racemosus Willd. that have been proposed to play role in the traditional medicine application of Ayurveda, as a “Rasayana” for rejuvenation by boosting the immune system, have been assessed in silico for immunomodulatory potential as therapeutic adjuvants in COVID-19 management . Rivero-Segura and Gomez-Verjan  have performed an in silico screening of 100 phytochemicals isolated from the most commonly used medicinal plants of Mexico for the SARS-CoV-2, and found ten compounds (emodin anthrone, kaempferol, quercetin, aesculin, cichoriin, luteolin, matricin, riolozatrione, monocaffeoyl tartaric acid, aucubin) that meet lead-likeness criteria. Figure 1 demonstrates several mechanisms of actions of traditional phytomedicines and phytoconstituents to perform anti-SARS-CoV-2 efficacy.
2.3.2 Role of ethnomedicinal plants in clinical trials for the treatment of COVID-19
It is worth mentioning that the efficacy of 32 Indian traditional medicinal plants against COVID-19 is registered for controlled clinical trial investigation which includes species, such as Tinospora cordifolia (Willd.) Miers stem, Piper longum L. fruit, ZingiVir (polyherbo-mineral drug), Chyawanprash (an Ayurvedic health supplement which is made up of a super-concentrated blend of nutrient-rich herbs and minerals), Aayudh Advance (an herbal formulation consisting of essential oils), and Ashwagandha (W. somnifera) (see ). Another clinical trial has also been registered (trial no: PACTR202012898601759) to evaluate the antiviral effect of the seed extract of Silybum marianum (L.) Gaertn. for the treatment of patients with COVID-19 in Nigeria (https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=14547). Milk thistle or Silybum marianum (L.) Gaertn. is a common herbal medicine species used around the world with wide ethnomedicinal usage and good clinical support .
A phytomedicine named “Cospherunate,” which is a combination of 50 mg Artesunate/125 mg Amodiaquine (Artemisia spp. and Artemisia derivatives), has been registered for clinical trials (ClinicalTrials.gov Identifier: NCT04502342) in therapy for COVID-19 treatment in Guinea. Additionally, other registered clinical trial interventions using Artemisia spp. and Artemisia derivatives in COVID-19 therapy have been listed . Artemisia vulgaris L., that is a traditional Chinese herb, has been reported to exhibit numerous potential health benefits .
In Thailand, Andrographis paniculata (Burm. f.) Nees has been approved for a pilot clinical trial in the treatment of mild COVID-19 symptoms , and another traditional herb, Boesenbergia rotunda (L.) Mansf., known as finger root, has been planned for human trial as the active ingredients in the plant were reported to eliminate SAS-CoV-2 in hamster experiments .
In Iran, the Food and Drug Administration has approved the use of four traditional herbal medicines in the treatment of COVID-19 , and clinical studies of licorice extracts, mallow (Malva sylvestris L.), echinacea, ginger, mixed with sage, fennel, and St. John’s wort, and Fluherb (grass extracts, plantain, isop, licorice, and turmeric, suspension) have been carried out to investigate effects in COVID-19 therapy . Furthermore, the herbal medicine Xagrotin, which is a combination of several local plants from the Zagros Mountains located in Kurdistan, has entered into clinical trial to evaluate outcome of patients with early-stage COVID-19 (https://clinicaltrials.gov/ct2/show/NCT05017493).
2.3.3 Role of ethnomedicinal plants in human gut microbiome against COVID-19
Targeting gut microbiota (GM) to prevent and treat COVID-19 has been viewed as an alternative strategy  as GM plays an important role in the maintenance of host homeostasis, and GM can modulate ACE2 which is expressed in intestinal cells and is crucial for the entry of SARS-CoV-2 into the host cells . Dysbiosis of GM or altered oral microbiome has a correlation with the severity and hospitalization of COVID-19 in patients compared to healthy individuals [125, 130] as well to produce pro-inflammatory cytokines . A systematic review has found imbalanced intestinal and respiratory microbiomes in hospitalized COVID-19 patients . Hence, COVID-19, as well as the post-COVID-19 gastrointestinal (GI) complications, has bidirectional interactions between the gut and lung microbial dysbiosis .
Medicinal plants that have supportive roles in immune stimulation and maintenance of a balanced gut microbiome may be effective strategies for the management of COVID-19  as a healthy gut microbiota is essential for a strong antiviral immunity . However, plant-based ethnomedicines are mostly ingested orally, and the efficacy of medicinal plants is regulated by the role of GM or GM-derived metabolites [105, 118]. Figure 2 illustrates how medicinal plants and the gut microbiome have potential roles in the attenuation of SARS-CoV-2 causing COVID-19. In general, orally administrated ethnomedicinal plants or ethnomedicinal phytochemicals are digested by gut microbiota-derived digestive enzymes (β-glucuronidase, β-glucosidase, and galactosidase) that facilitate biotransformation into the absorbable bioactive components with potent bioactivities and then enter the body and induce pharmacological effects [14, 124]. Hence, traditional phytomedicines have the ability to change the composition of GM and its secretions which later induce physiochemical changes as well .
It is worth noting that the potential role of GM in traditional Chinese herbal medicines for the attenuation of SARS-CoV-2 has been demonstrated earlier (see ). On the other hand, Chen et al. have reviewed and listed the roles of medicinal plants to include ACE2 inhibition in the GI tract, support in restoration of the GI flora for the regulation of intestinal mucosal barrier and respiratory immunity, and the attenuators of the specific complexities that caused by COVID-19 disease .
2.3.4 Role of ethnomedicinal plants as immunomodulation against COVID-19
As ethnomedicinal plants are potential and promising sources of immunomodulators against COVID-19, ethnomedicinal plants such as Panax ginseng C.A.Mey., Achillea millefolium L., Andrographis paniculata (Burm. f.) Nees, Asperagus racemosus Willd., Bauhinia variegate L., Hyptis suaveolens (L.) Poit., Cleome gynandra L., Alternanthera tenella Colla, Abutilon indicum (L.) Sweet, Heracleum persicum Desf. ex Fisch., C.A.Mey. & Avé-Lall., Lagenaria siceraria (Molina) Standl., and Chlorophytum borivilianum Santapau & R.R.Fern. are considered immunomodulators and reported for enhancing the body’s stamina to fight against COVID-19 . Notably, Silveira and colleagues have identified a total of 39 herbal medicines that were found to be very promising for COVID-19 patients, and out of 39 species they suggested Althaea officinalis L., Commiphora molmol (Engl.) Engl. ex Tschirch, Glycyrrhiza glabra L., Hedera helix L., and Sambucus nigra L. for safety and use as adjuvants in the treatment of early/mild symptoms of COVID-19 . The mechanisms underlying immunomodulatory activities of medicinal plants and their bioactive phytoconstituents are (1): activation of NK cells, macrophages, neutrophils and eosinophils, (2): simulation of signaling molecules (NF-kB, JNK, P38, ERK), (3): expression of cytokines (TNF-α, IL-6, IL-8), (4): expression of chemokines (CCL4, CCL8), (5): promotion of T-lymphocytes, transformation to T-helper cells, (6): inhibition of pro-inflammatory chemicals . Figure 3 portrays the recent advances in traditional phytomedicines against SARS-CoV-2.
Ang et al.  have found 9 guidelines of herbal formulas (mostly based on clinical results) recommended for the medical observation period of COVID-19, of which 8 were issued by the Chinese provincial government for 12 herbal formulas and 1 was issued by the Korean Pulmonary Association of Traditional Medicine for 2 herbal formulas. Antiviral traditional medicinal plants have broad-spectrum activities such as viral attachment inhibition of the host cell, viral replication inhibition, downregulation of translation of viral proteins and virus-induced pro-inflammatory/inflammatory signaling pathways in the host cell, suppression of RNA replication, as well as activities as antioxidants to inhibit virus-induced oxidative stress .
Numerous in silico studies on traditional medicinal plants and secondary metabolites have been performed in the search for potent COVID-19 therapeutics, of which only a few have in vitro or in vivo antiviral activity; some of these are registered for controlled clinical trials. The reliance on ethnomedicinal plants is suddenly advanced due to the outbreak of a new coronavirus, SARS-CoV-2, as medicinal plants can target and inhibit viral 3CLPro, spike proteins, main protease, RDRP, and host TMPRSS2 protease, ACE2 receptor. Moreover, ethno-phytomedicine has roles in the gut microbiome and immunomodulatory activity for the potential biotherapeutic efficacy against COVID-19. We have identified 16 plant species (A. sativum, A. paniculata, A. herba-alba, A. vulgaris, A. indica, C. sinensis, C. limon, C. longa, E. globulus, E. hirta, G. glabra, M. indica, N. sativa, P. guajava, S. aromaticum, and Z. officinale) that are the most commonly used traditional phytomedicine for COVID-19 prevention and treatment in various geographical locations. These plant species have reported in vitro, in vivo, and in silico antiviral efficacy with diverse mechanisms (such as inhibition or blocking viral entry into host cells, viral RNA polymerase and RNA replication, viral DNA synthesis, viral hemagglutination, viral assembly, disruption of viral membrane proteins, enhancing cytotoxic T cells, natural killer (NK) cells, and phagocytosis). Due to these advances in understanding, there should be enhanced recognition for extensive biological research of ethnomedicines for developing plant-based COVID-19 eradication strategies.
According to the above discussions, the necessity to build collaborations among those with ethnomedicinal plants knowledge, scientists, and technologists to develop the most efficient and the safest adjuvant therapeutics against the pandemic of the twenty-first century, COVID-19, has been realized.
Availability of data and materials
Angiotensin-converting enzyme 2
Transmembrane serine protease 2
- 3CLPro/Mpro :
- PLPro :
RNA-dependent RNA polymerase
Absorption, distribution, metabolism, excretion, and toxicity
Abd EI-Wahab A, EI-Adawi H, EI-Demellawy MM (2009) In vitro study of the antiviral activity of Zingiber officinale. Planta Med. https://doi.org/10.1055/s-0029-1234649
Adeleye OA, Femi-Oyewo MN, Bamiro OA et al (2021) Ethnomedicinal herbs in African traditional medicine with potential activity for the prevention, treatment, and management of coronavirus disease 2019. Future J Pharm Sci 7:72. https://doi.org/10.1186/s43094-021-00223-5
Adhikari B, Marasini BP, Rayamajhee B et al (2021) Potential roles of medicinal plants for the treatment of viral diseases focusing on COVID-19: a review. Phytother Res 35(3):1298–1312. https://doi.org/10.1002/ptr.6893
Ahmad SR (2021) Medicinal plants—derived natural products and phytochemical extract as potential therapies for coronavirus: future perspective. Biomed Pharmacol J. https://doi.org/10.13005/bpj/2181
Ahmadi Badi S, Tarashi S, Fateh A, Rohani P, Masotti A, Siadat SD (2021) From the role of microbiota in gut-lung axis to SARS-CoV-2 pathogenesis. Mediat Inflamm. https://doi.org/10.1155/2021/6611222
Ahmed MN, Jahan R, Nissapatorn V, Wilairatana P, Rahmatullah M (2022) Plant lectins as prospective antiviral biomolecules in the search for COVID-19 eradication strategies. Biomed Pharmacother 146:112507. https://doi.org/10.1016/j.biopha.2021.112507
Alagu Lakshmi S, Shafreen RMB, Priya A, Shunmugiah KP (2021) Ethnomedicines of Indian origin for combating COVID-19 infection by hampering the viral replication: using structure-based drug discovery approach. J Biomol Struct Dyn 39(13):4594–4609. https://doi.org/10.1080/07391102.2020.1778537
Alam MA, Parra-Saldivar R, Bilal M et al (2021) Algae-derived bioactive molecules for the potential treatment of SARS-CoV-2. Molecules 26(8):2134. https://doi.org/10.3390/molecules26082134
Alam S, Sarker MdMR, Afrin S, Richi FT, Zhao C, Zhou J-R, Mohamed IN (2021a) Traditional herbal medicines, bioactive metabolites, and plant products against covid-19: update on clinical trials and mechanism of actions. Front Pharmacol 12:671498. https://doi.org/10.3389/fphar.2021.671498
Alhazmi HA, Najmi A, Javed SA, Sultana S, Al Bratty M, Makeen HA, Meraya AM, Ahsan W, Mohan S, Taha MME, Khalid A (2021) Medicinal plants and isolated molecules demonstrating immunomodulation activity as potential alternative therapies for viral diseases including covid-19. Front Immunol 12:637553. https://doi.org/10.3389/fimmu.2021.637553
Amber R, Adnan M, Tariq A, Mussarat S (2017) A review on antiviral activity of the Himalayan medicinal plants traditionally used to treat bronchitis and related symptoms. J Pharm Pharmacol 69(2):109–122. https://doi.org/10.1111/jphp.12669
Al Rawi AAS, Al Dulaimi HSH, Al Rawi MAA (2019) Antiviral activity of mangifera extract on influenza virus cultivated in different cell cultures. J Pure Appl Microbiol 13(1):455–458. https://doi.org/10.22207/JPAM.13.1.50
Amparo TR, Seibert JB, Silveira BM, Costa F, Almeida TC, Braga S, da Silva GN, Dos Santos O, de Souza G (2021) Brazilian essential oils as source for the discovery of new anti-COVID-19 drug: a review guided by in silico study. Phytochem Rev Proc Phytochem Soc Europe 20(5):1013–1032. https://doi.org/10.1007/s11101-021-09754-4
An X, Bao Q, Di S, Zhao Y, Zhao S, Zhang H, Lian F, Tong X (2019) The interaction between the gut Microbiota and herbal medicines. Biomed Pharmacother 118:109252. https://doi.org/10.1016/j.biopha.2019.109252
Ang L, Lee HW, Kim A, Lee MS (2020) Herbal medicine for the management of COVID-19 during the medical observation period: a review of guidelines. Integr Med Res 9(3):100465. https://doi.org/10.1016/j.imr.2020.100465
Asif M, Saleem M, Saadullah M et al (2020) COVID-19 and therapy with essential oils having antiviral, anti-inflammatory, and immunomodulatory properties. Inflammopharmacol 28:1153–1161. https://doi.org/10.1007/s10787-020-00744-0
Aswandi A, Kholibrina CR (2021) Ethnopharmacological properties of essential oils from natural forests in Northern Sumatra. IOP Conf Ser Earth Environ Sci 715:012077
Attah AF, Fagbemi AA, Olubiyi O et al (2021) Therapeutic potentials of antiviral plants used in traditional african medicine with COVID-19 in focus: a Nigerian perspective. Front Pharmacol 12:596855. https://doi.org/10.3389/fphar.2021.596855
Azimi M, Mojahedi M, Mokaberinejad R, Hasheminasab FS (2021) Ethnomedicine knowledge of iranian traditional healers and the novel coronavirus disease 2019 (COVID-19). J Adv Med Biomed Res 29(135):238–245
Battistini R, Rossini I, Ercolini C et al (2019) Antiviral activity of essential oils against hepatitis a virus in soft fruits. Food Environ Virol 11(1):90–95. https://doi.org/10.1007/s12560-019-09367-3
Belhaj S, Zidane L (2021) Medicinal plants used to boost immunity and decrease the intensity of infection caused by SARS-COV-2 in morocco. Ethnobot Res App 21:1–17. https://doi.org/10.32859/era.21.41.1-17
Belmouhoub M, Aberkane B, Bachir bey M (2021) Ethnopharmacological survey on medicinal plants used by Algerian population to prevent SARS-CoV-2 infection. Ethnobot Res App 22:1–13. https://doi.org/10.32859/era.22.38.1-13
Bellik Y, Bey MB, Fatmi W, Kouidri M, Souagui Y, Ammar Selles SM (2020) Micronutrients and phytochemicals against COVID-19: mechanism and molecular targets. Ann Phytomed Int J 9(2):15–29. https://doi.org/10.21276/ap.2020.9.2.3
Benarba B, Pandiella A (2020) Medicinal plants as sources of active molecules against COVID-19. Front Pharmaco 11:1189. https://doi.org/10.3389/fphar.2020.01189
Benkhaira N, Ibnsouda Koraichi S, Fikri-Benbrahim K (2021) Ethnobotanical survey on plants used by traditional healers to fight against COVID-19 in Fez city, Northern Morocco. Ethnobot Res App 21:1–18. https://doi.org/10.32859/era.21.27.1-18
Bloomberg News (2020) Herbal Covid treatment cleared, vaccine registration opens. https://www.bangkokpost.com/thailand/general/2043519/herbal-covid-treatment-cleared-vaccine-registration-opens. Accessed 5 Oct 2021
Boozari M, Hosseinzadeh H (2021) Natural products for COVID -19 prevention and treatment regarding to previous coronavirus infections and novel studies. Phytother Res 35(2):864–876. https://doi.org/10.1002/ptr.6873
Borkotoky S, Banerjee M (2021) A computational prediction of SARS-CoV-2 structural protein inhibitors from Azadirachta indica (Neem). J Biomol Struct Dyn 39(11):4111–4121. https://doi.org/10.1080/07391102.2020.1774419
Borse S, Joshi M, Saggam A et al (2021) Ayurveda botanicals in COVID-19 management: an in silico multi-target approach. PLoS ONE 16(6):e0248479. https://doi.org/10.1371/journal.pone.0248479
Brezáni V, Veronika L, Sherif TSH, Kateřina B, Pavel N, Pavel K, Petr M, Stefano D, Jan H, Karel Š (2018) Anti-infectivity against herpes simplex virus and selected microbes and anti-inflammatory activities of compounds isolated from Eucalyptus globulus Labill. Viruses 10(7):360. https://doi.org/10.3390/v10070360
Bouafia M, Amamou F, Gherib M et al (2021) Ethnobotanical and ethnomedicinal analysis of wild medicinal plants traditionally used in Naâma, southwest Algeria. Vegetos 34:654–662. https://doi.org/10.1007/s42535-021-00229-7
Chaachouay N, Douira A, Zidane L (2021) COVID-19, prevention and treatment with herbal medicine in the herbal markets of Salé Prefecture, North-Western Morocco. Eur J Integr Med 42:101285. https://doi.org/10.1016/j.eujim.2021.101285
Chandramouli V, Niraj SK, Nair KG, Joseph J, Aruni W (2021) Phytomolecules repurposed as Covid-19 inhibitors: opportunity and challenges. Curr Microbiol 78(10):3620–3633. https://doi.org/10.1007/s00284-021-02639-x
Chang JS, Wang KC, Yeh CF, Shieh DE, Chiang LC (2013) Fresh ginger (Zingiber officinale) has anti-viral activity against human respiratory syncytial virus in human respiratory tract cell lines. J Ethnopharmacol 145(1):146–151. https://doi.org/10.1016/j.jep.2012.10.043
Chen Z, Lv Y, Xu H, Deng L (2021) Herbal medicine, gut microbiota, and COVID-19. Front Pharmacol 12:646560. https://doi.org/10.3389/fphar.2021.646560
Chhibber-Goel J, Gopinathan S, Sharma A (2021) Interplay between severities of COVID-19 and the gut microbiome: implications of bacterial co-infections? Gut Pathog 13:14. https://doi.org/10.1186/s13099-021-00407-7
Chikowe I, Mtewa AG, Tembo D, Smith D, Ibrahim E, Mwamatope B, Maroyi A (2021) Potential of Malawi’s medicinal plants in Covid-19 disease management: a review. Malawi Med J 33(2):85–107. https://doi.org/10.4314/mmj.v33i2.4
Cortés-Rojas DF, de Souza CR, Oliveira WP (2014) Clove (Syzygium aromaticum): a precious spice. Asian Pac J Trop Biomed 4(2):90–96. https://doi.org/10.1016/S2221-1691(14)60215-X
Das G, Heredia JB, de Lourdes PM et al (2021) Korean traditional foods as antiviral and respiratory disease prevention and treatments: a detailed review. Trends Food Sci Technol 116:415–433. https://doi.org/10.1016/j.tifs.2021.07.037
De Meyer E, Van Damme P, de la Peña E, Ceuterick M (2022) “A disease like any other” traditional, complementary and alternative medicine use and perspectives in the context of COVID-19 among the Congolese community in Belgium. J Ethnobiol Ethnomed 18(1):29. https://doi.org/10.1186/s13002-022-00530-y
Dibazar SP, Fateh S, Daneshmandi S (2015) Immunomodulatory effects of clove (Syzygium aromaticum) constituents on macrophages: in vitro evaluations of aqueous and ethanolic components. J Immunotoxicol 12(2):124–131. https://doi.org/10.3109/1547691X.2014.912698
Din M, Zia F, Khalil AT, Ali M, Shinwari ZK (2021) Functional Food Plants and their Potential Antiviral and Immunomodulatory Properties: the Covid-19 Perspective. Proc Pak Acad Sci Part B 58(Special Issue B):1–10
Dwarka D, Agoni C, Mellem JJ, Soliman ME, Baijnath H (2020) Identification of potential SARS-CoV-2 inhibitors from South African medicinal plant extracts using molecular modelling approaches. S Afr J Bot 133:273–284. https://doi.org/10.1016/j.sajb.2020.07.035
El Alami A, Fattah A, Chait A (2020) Medicinal plants used for the prevention purposes during the Covid-19 pandemic in Morocco. J Anal Sci Appl Biotechnol 2(1):4–11
El-Darier SM, Rashed SA, Fayez A, Hassanein SS, Sharaby MR, Noran MT, Heba M, Mohamed A (2021) Medicinal plant-derived compounds as potential phytotherapy for COVID-19: future perspectives. J Pharmacogn Phytother 13(3):68–81
FB/MG (2020) Iran finds herbal medicines effective in COVID-19 treatment. https://www.tehrantimes.com/news/454442/Iran-finds-herbal-medicines-effective-in-COVID-19-treatment#. Accessed 8 Oct 2021
Flórez-Álvarez L, Martínez-Moreno J, Zapata-Cardona MI, Galeano E, Alzate-Guarin F, Zapata W (2022) In vitro antiviral activity against SARS-CoV-2 of plant extracts used in Colombian traditional medicine. Vitae. https://doi.org/10.17533/udea.vitae.v29n1a347854
Fongnzossie Fedoung E, Biwole AB, Nyangono Biyegue CF et al (2021) A review of Cameroonian medicinal plants with potentials for the management of the COVID-19 pandemic. Adv Tradit Med. https://doi.org/10.1007/s13596-021-00567-6
Frost R, Bhamra SK, Pendry B, Heinrich M (2021) Covid-19 and herbal practice: a UK practitioner survey. Adv Integr Med. https://doi.org/10.1016/j.aimed.2021.09.003
Grigore A, Cord D, Tanase C, Albulescu R (2020) Herbal medicine, a reliable support in COVID therapy. J Immunoassay Immunochem 41(6):976–999. https://doi.org/10.1080/15321819.2020.1862867
Gupta S, Mishra KP, Ganju L (2017) Broad-spectrum antiviral properties of andrographolide. Arch Virol 162(3):611–623. https://doi.org/10.1007/s00705-016-3166-3
Gyuris A, Szlávik L, Minárovits J, Vasas A, Molnár J, Hohmann J (2009) Antiviral activities of extracts of Euphorbia hirta L. against HIV-1, HIV-2 and SIVmac251. In Vivo 23(3):429–432
Hafez Ghoran S, El-Shazly M, Sekeroglu N, Kijjoa A (2021) Natural products from medicinal plants with anti-human coronavirus activities. Molecules 26(6):1754. https://doi.org/10.3390/molecules26061754
Haidara M, Diarra ML, Doumbia S, Denou A, Dembele D, Diarra B, Sanogo R (2020) Medicinal plants from West Africa for the management of respiratory diseases that may appear during the Covid-19. Int J Biol Chem Sci 14(8):2941–2950 (Article in French)
Hasan A, Biswas P, Bondhon TA, Jannat K, Paul TK, Paul AK, Jahan R, Nissapatorn V, Mahboob T, Wilairatana P, Hasan MN, de Lourdes PM, Wiart C, Rahmatullah M (2022) Can Artemisia herba-alba be useful for managing COVID-19 and comorbidities? Molecules 27(2):492. https://doi.org/10.3390/molecules27020492
Heiat M, Hashemi-Aghdam MR, Heiat F et al (2021) Integrative role of traditional and modern technologies to combat COVID-19. Expert Rev Anti Infect Ther 19(1):23–33. https://doi.org/10.1080/14787210.2020.1799784
Hossain S, Jahan R, Hasan A, Jannat K, Bondhon TA, Rahmatullah M (2020) Spices and plants as home remedies for COVID-19: a survey in Rajbari District, Bangladesh. J Nat Ayurvedic Med 4(3):000268
Jadhav AK, Karuppayil SM (2021) Andrographis paniculata (Burm. F) Wall ex Nees: antiviral properties. Phytother Res. https://doi.org/10.1002/ptr.7145
Jahan R, Paul AK, Jannat K, Rahmatullah M (2021) Plant essential oils: possible COVID-19 therapeutics. Nat Prod Commun 16(2):1
Javed H, Meeran MFN, Jha NK, Ojha S (2021) Carvacrol, a plant metabolite targeting viral protease (Mpro) and ACE2 in host cells can be a possible candidate for COVID-19. Front Plant Sci 11:601335. https://doi.org/10.3389/fpls.2020.601335
Karataş Y, Khan Z, Bilen C, Boz A et al (2021) Traditional and complementary medicine use and beliefs during COVID-19 outbreak: a cross-sectional survey among the general population in Turkey. Adv Integr Med. https://doi.org/10.1016/j.aimed.2021.09.002
Kaur M, Devi G, Nagpal M, Singh M, Dhingra GA, Aggarwal G (2020) Antiviral essential oils incorporated in nanocarriers: strategy for prevention from COVID-19 and future infectious pandemics. Pharm Nanotechnol 8(6):437–451. https://doi.org/10.2174/2211738508666201016151850
Khabour OF, Hassanein SFM (2021) Use of vitamin/zinc supplements, medicinal plants, and immune boosting drinks during COVID-19 pandemic: a pilot study from Benha city. Egypt Heliyon 7(3):e06538. https://doi.org/10.1016/j.heliyon.2021.e06538
Khadka D, Dhamala MK, Li F et al (2021) The use of medicinal plants to prevent COVID-19 in Nepal. J Ethnobiol Ethnomed 17:26. https://doi.org/10.1186/s13002-021-00449-w
Khan T, Khan MA, Mashwani ZU, Ullah N, Nadhman A (2021) Therapeutic potential of medicinal plants against COVID-19: the role of antiviral medicinal metabolites. Biocatal Agric Biotechnol 31:101890. https://doi.org/10.1016/j.bcab.2020.101890
Khan MF, Khan MA, Khan ZA, Ahamad T, Ansari WA (2021) In-silico study to identify dietary molecules as potential SARS-CoV-2 agents. Lett Drug Des Discov 18(6):562–573
Kshirsagar SG, Rao RV (2021) Antiviral and immunomodulation effects of Artemisia. Medicina (Kaunas) 57(3):217. https://doi.org/10.3390/medicina57030217
Kulkarni SA, Nagarajan SK, Ramesh V, Palaniyandi V, Selvam SP, Madhavan T (2020) Computational evaluation of major components from plant essential oils as potent inhibitors of SARS-CoV-2 spike protein. J Mol Struct 1221:128823. https://doi.org/10.1016/j.molstruc.2020.128823
Lawal IO, Omogbene TO (2021) Nigerian polyherbal-based hydrotherapy: a panacea to infectious diseases. Herba Polonica 67(2):65–79. https://doi.org/10.2478/hepo-2021-0007
Luo L, Jiang J, Wang C, Fitzgerald M, Hu W, Zhou Y, Zhang H, Chen S (2020) Analysis on herbal medicines utilized for treatment of COVID-19. Acta Pharm Sin B 10(7):1192–1204. https://doi.org/10.1016/j.apsb.2020.05.007
Maharani R, Fernandes A (2021) The potential of herbal medicine from Kalimantan, Indonesia, to stimulate human immunity during the COVID-19 pandemic: a brief overview. Ann Phytomed 10(1):S115–S120
Malekmohammad K, Rafieian-Kopaei M (2021) Mechanistic aspects of medicinal plants and secondary metabolites against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Curr Pharm Des. https://doi.org/10.2174/1381612827666210705160130.10.2174/1381612827666210705160130
Mhatre S, Srivastava T, Naik S, Patravale V (2021) Antiviral activity of green tea and black tea polyphenols in prophylaxis and treatment of COVID-19: a review. Phytomedicine 85:153286. https://doi.org/10.1016/j.phymed.2020.153286
Muthumanickam S, Kamaladevi A, Boomi P, Gowrishankar S, Pandian SK (2021) Indian ethnomedicinal phytochemicals as promising inhibitors of rna-binding domain of SARS-CoV-2 nucleocapsid phosphoprotein: an in silico study. Front Mol Biosci 8:637329. https://doi.org/10.3389/fmolb.2021.637329
Oladele JO, Ajayi EI, Oyeleke OM et al (2020) A systematic review on COVID-19 pandemic with special emphasis on curative potentials of Nigeria based medicinal plants. Heliyon 6(9):e04897. https://doi.org/10.1016/j.heliyon.2020.e04897
Omrani M, Keshavarz M, Nejad Ebrahimi S, Mehrabi M, McGaw LJ, Ali Abdalla M, Mehrbod P (2021) Potential natural products against respiratory viruses: a perspective to develop anti-COVID-19 medicines. Front Pharmacol 11:586993. https://doi.org/10.3389/fphar.2020.586993
Orege JI, Adeyemi SB, Tiamiyu BB, Akinyemi TO, Ibrahim YA, Orege OB (2021) Artemisia and Artemisia-based products for COVID-19 management: current state and future perspective. Adv Tradit Med. https://doi.org/10.1007/s13596-021-00576-5
Panikar S, Shoba G, Arun M et al (2021) Essential oils as an effective alternative for the treatment of COVID-19: molecular interaction analysis of protease (Mpro) with pharmacokinetics and toxicological properties. J Infect Public Health 14(5):601–610. https://doi.org/10.1016/j.jiph.2020.12.037
Phumthum M, Nguanchoo V, Balslev H (2021) Medicinal plants used for treating mild covid-19 symptoms among Thai Karen and Hmong. Front Pharmacol 12:699897. https://doi.org/10.3389/fphar.2021.699897
Pieroni A, Vandebroek I, Prakofjewa J et al (2020) Taming the pandemic? The importance of homemade plant-based foods and beverages as community responses to COVID-19. J Ethnobiol Ethnomed 16:75. https://doi.org/10.1186/s13002-020-00426-9
Prasad A, Muthamilarasan M, Prasad M (2020) Synergistic antiviral effects against SARS-CoV-2 by plant-based molecules. Plant Cell Rep 39(9):1109–1114. https://doi.org/10.1007/s00299-020-02560-w
Prasansuklab A, Theerasri A, Rangsinth P, Sillapachaiyaporn C, Chuchawankul S, Tencomnao T (2021) Anti-COVID-19 drug candidates: a review on potential biological activities of natural products in the management of new coronavirus infection. J Tradit Complement Med 11(2):144–157. https://doi.org/10.1016/j.jtcme.2020.12.001
Quinlan MB (2011) Ethnomedicine. In: A companion to medical anthropology (eds M. Singer and P.I. Erickson). https://doi.org/10.1002/9781444395303.ch19
Rastogi S, Pandey DN, Singh RH (2020) COVID-19 Pandemic: a pragmatic plan for Ayurveda Intervention. J Ayurveda Integr Med. https://doi.org/10.1016/j.jaim.2020.04.002
Reichling J (2021) Antiviral and virucidal properties of essential oils and isolated compounds—a scientific approach. Planta Med. https://doi.org/10.1055/a-1382-2898.10.1055/a-1382-2898
Researchers at East Kent Hospitals (2021) East Kent researchers’ trial black elderberry liquid as a treatment for Covid-19. https://www.ekhuft.nhs.uk/patients-and-visitors/news-centre/latest-news/east-kent-researchers-trial-black-elderberry-liquid-as-a-treatment-for-covid-19/. Accessed 27 Sept 2021
Rivero-Segura NA, Gomez-Verjan JC (2021) In silico screening of natural products isolated from mexican herbal medicines against covid-19. Biomolecules 11(2):216. https://doi.org/10.3390/biom11020216
Rouf R, Uddin SJ, Sarker DK et al (2020) Antiviral potential of garlic (Allium sativum) and its organosulfur compounds: a systematic update of pre-clinical and clinical data. Trends Food Sci Technol 104:219–234. https://doi.org/10.1016/j.tifs.2020.08.006
Saied AA, Metwally AA, Madkhali NAB, Haque S, Dhama K (2021) Egypt’s COVID-19 recent happenings and perspectives: a mini-review. Front Public Health 9:696082. https://doi.org/10.3389/fpubh.2021.696082
Salem MA, Ezzat SM (2021) The use of aromatic plants and their therapeutic potential as antiviral agents: a hope for finding anti-COVID 19 essential oils. J Essent Oil Res 33(2):105–113. https://doi.org/10.1080/10412905.2021.1886187
Sargin SA (2021) Potential anti-influenza effective plants used in Turkish folk medicine: a review. J Ethnopharmacol 265:113319. https://doi.org/10.1016/j.jep.2020.113319
Shakil SSM, Gowan M, Hughes K, Azam MNK, Ahmed MN (2021) A narrative review of the ethnomedicinal usage of Cannabis sativa Linnaeus as traditional phytomedicine by folk medicine practitioners of Bangladesh. J Cannabis Res 3(1):8. https://doi.org/10.1186/s42238-021-00063-3
Sharma A, Rani S (2021) Immunity booster plants from traditional knowledge in north Indian plains to mitigate COVID-19 infestation. J Indian Bot Soc 101(1):16–30
Sharifi-Rad J et al (2017) Biological activities of essential oils: from plant chemoecology to traditional healing systems. Molecules (Basel, Switzerland) 22(1):70. https://doi.org/10.3390/molecules22010070
Shoaib A, Azmi L, Shukla I, Alqahtani SS, Alsarra IA, Shakeel F (2021) Properties of ethnomedicinal plants and their bioactive compounds: possible use for COVID-19 prevention and treatment. Curr Pharm Des 27(13):1579–1587. https://doi.org/10.2174/1381612826666201106092021
Silveira D, Prieto-Garcia JM, Boylan F et al (2020) COVID-19: is there evidence for the use of herbal medicines as adjuvant symptomatic therapy? Front Pharmacol 11:581840. https://doi.org/10.3389/fphar.2020.581840
Singh RK, Lego YJ, Sureja AK, Srivastava RC, Hazarika BN (2021) People and plant: learning with Adi community on ethnomedicinal practices and conservation in Arunachal Pradesh, India. Indian J Tradit Knowl 20(1):74–82
Singh RS, Singh A, Kaur H et al (2021) Promising traditional Indian medicinal plants for the management of novel Coronavirus disease: a systematic review. Phytother Res 35(8):4456–4484. https://doi.org/10.1002/ptr.7150
Singirikonda S, Khan MS, Das K, Tejashwini R, Jothi A (2021) Edible dry fruits and seeds in combating second wave of COVID-19 pandemic. Ann Phytomed 10:S130–S145. https://doi.org/10.21276/ap.covid19.2021.10.1.13
Soon L, Ng PQ, Chellian J et al (2019) Therapeutic potential of Artemisia vulgaris: an insight into underlying immunological mechanisms. J Environ Pathol Toxicol Oncol 38(3):205–216. https://doi.org/10.1615/JEnvironPatholToxicolOncol.2019029397
Spagnolello O, Pinacchio C, Santinelli L et al (2021) Targeting microbiome: an alternative strategy for fighting SARS-CoV-2 infection. Chemotherapy 66(1–2):24–32. https://doi.org/10.1159/000515344
Sriwilaijaroen N, Fukumoto S, Kumagai K et al (2012) Antiviral effects of Psidium guajava Linn (guava) tea on the growth of clinical isolated H1N1 viruses: its role in viral hemagglutination and neuraminidase inhibition. Antiviral Res 94(2):139–146. https://doi.org/10.1016/j.antiviral.2012.02.013
Tegen D, Dessie K, Damtie D (2021) Candidate anti-COVID-19 medicinal plants from Ethiopia: a review of plants traditionally used to treat viral diseases. Evid-based Complem Altern Med. https://doi.org/10.1155/2021/6622410
Thimmulappa RK, Mudnakudu-Nagaraju KK, Shivamallu C et al (2021) Antiviral and immunomodulatory activity of curcumin: a case for prophylactic therapy for COVID-19. Heliyon 7(2):e06350. https://doi.org/10.1016/j.heliyon.2021.e06350
Thumann TA, Pferschy-Wenzig EM, Moissl-Eichinger C, Bauer R (2019) The role of gut microbiota for the activity of medicinal plants traditionally used in the European Union for gastrointestinal disorders. J Ethnopharmacol 245:112153. https://doi.org/10.1016/j.jep.2019.112153
Tiwari V, Darmani NA, Yue BY, Shukla D (2010) In vitro antiviral activity of neem (Azardirachta indica L.) bark extract against herpes simplex virus type-1 infection. Phytother Res 24(8):1132–1140. https://doi.org/10.1002/ptr.3085
Tiwari S, Dubey NK (2020) Traditional medicinal plants as promising source of immunomodulator against covid-19. J Exp Biol Agric Sci 8(2):S126–S138. https://doi.org/10.18006/2020.8(Spl-1-SARS-CoV-2).S126.S138
Tsouh Fokou PV, Youmsi Fokouo RD (2020) Exploring the indigenous knowledge systems to respond to coronavirus infection 2019 in Cameroon. Ethnobot Res Appl 20:1–27
Ugwah-Oguejiofor CJ, Adebisi IM (2021) Potential medicinal plant remedies and their possible mechanisms against COVID-19 review. IFE J Sci 23(1):161–194. https://doi.org/10.4314/ijs.v23i1.16
Umeta Chali B, Melaku T, Berhanu N, Mengistu B, Milkessa G, Mamo G, Alemu S, Mulugeta T (2021) Traditional medicine practice in the context of COVID-19 pandemic: community claim in Jimma Zone, Oromia, Ethiopia. Infect Drug Resist 14:3773–3783. https://doi.org/10.2147/IDR.S331434
Valussi M, Antonelli M, Donelli D, Firenzuoli F (2021) Appropriate use of essential oils and their components in the management of upper respiratory tract symptoms in patients with COVID-19. J Herb Med 28:100451. https://doi.org/10.1016/j.hermed.2021.100451
Vandebroek I, Pieroni A, Stepp JR et al (2020) Reshaping the future of ethnobiology research after the COVID-19 pandemic. Nat Plants 6:723–730. https://doi.org/10.1038/s41477-020-0691-6
van de Sand L, Bormann M, Alt M et al (2021) Glycyrrhizin effectively inhibits SARS-CoV-2 replication by inhibiting the viral main protease. Viruses 13(4):609. https://doi.org/10.3390/v13040609
Verma S, Twilley D, Esmear T et al (2020) Anti-SARS-CoV natural products with the potential to inhibit SARS-CoV-2 (COVID-19). Front Pharmacol 11:561334. https://doi.org/10.3389/fphar.2020.561334
Villena-Tejada M, Vera-Ferchau I, Cardona-Rivero A et al (2021) Use of medicinal plants for COVID-19 prevention and respiratory symptom treatment during the pandemic in Cusco, Peru: a cross-sectional survey. PLoS ONE 16(9):e0257165. https://doi.org/10.1371/journal.pone.0257165
Vroh BTA (2020) Diversity of plants used in traditional medicine against the main symptoms of COVID-19 in sub-Saharan Africa: review of the literature. Ethnobot Res App 20:1–14
Wang RR, Gao YD, Ma CH et al (2011) Mangiferin, an anti-HIV-1 agent targeting protease and effective against resistant strains. Molecules 16(5):4264–4277. https://doi.org/10.3390/molecules16054264
Wang Y, Qin S, Jia J, Huang L, Li F, Jin F, Ren Z, Wang Y (2019) Intestinal microbiota- associated metabolites: crucial factors in the effectiveness of herbal medicines and diet therapies. Front Physiol 10:1343. https://doi.org/10.3389/fphys.2019.01343
Wang YQ, Li QS, Zheng XQ, Lu JL, Liang YR (2021) Antiviral effects of green tea EGCG and its potential application against COVID-19. Molecules 26(13):3962. https://doi.org/10.3390/molecules26133962
Wani AR, Yadav K, Khursheed A, Rather MA (2021) An updated and comprehensive review of the antiviral potential of essential oils and their chemical constituents with special focus on their mechanism of action against various influenza and coronaviruses. Microb Pathog 152:104620. https://doi.org/10.1016/j.micpath.2020.104620
WHO Africa (2020) WHO supports scientifically-proven traditional medicine. https://www.afro.who.int/news/who-supports-scientifically-proven-traditional-medicine. Accessed 27 Sept 2021
Wilkin PJ, Al-Yozbaki M, George A, Gupta GK, Wilson CM (2020) The undiscovered potential of essential oils for treating SARS-CoV-2 (COVID-19). Curr Pharm Des 26:5261–5277. https://doi.org/10.2174/1381612826666201015154611
Wipatayotin A (2020) Researchers pin hopes on 'herbal cure'. https://www.bangkokpost.com/thailand/general/2037759/researchers-pin-hopes-on-herbal-cure. Assessed 6 Oct 2021
Wu XM, Tan RX (2019) Interaction between gut microbiota and ethnomedicine constituents. Nat Prod Rep 36(5):788–809. https://doi.org/10.1039/c8np00041g
Wu Y, Cheng X, Jiang G et al (2021) Altered oral and gut microbiota and its association with SARS-CoV-2 viral load in COVID-19 patients during hospitalization. npj Biofilms Microbiomes 7:61. https://doi.org/10.1038/s41522-021-00232-5
Yadalam PK, Varatharajan K, Rajapandian K et al (2021) Antiviral essential oil components against SARS-CoV-2 in pre-procedural mouth rinses for dental settings during COVID-19: a computational study. Front Chem 9:642026. https://doi.org/10.3389/fchem.2021.642026
Yamamoto S, Saito M, Tamura A, Prawisuda D, Mizutani T, Yotsuyanagi H (2021) The human microbiome and COVID-19: a systematic review. PLoS ONE 16(6):e0253293. https://doi.org/10.1371/journal.pone.0253293
Yang F, Zhang Y, Tariq A et al (2020) Food as medicine: a possible preventive measure against coronavirus disease (COVID-19). Phytother Res 34:3124–3136. https://doi.org/10.1002/ptr.6770
Yashvardhini N, Samiksha S, Jha D (2021) Pharmacological intervention of various Indian medicinal plants in combating COVID-19 infection. Biomed Res Ther 8(7):4461–4475. https://doi.org/10.15419/bmrat.v8i7.685
Yeoh YK, Zuo T, Lui GC et al (2021) Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19. Gut 70:698–706. https://doi.org/10.1136/gutjnl-2020-323020
Zahra N (2017) A short review on ethnomedicinal uses and phytochemistry of silybum marianum. Nat Prod Chem Res 5:1–3
Zareie A, Soleimani D, Askari G et al (2021) Cinnamon: a promising natural product against COVID-19. Adv Exp Med Biol 1327:191–195. https://doi.org/10.1007/978-3-030-71697-4_15
Zhang Q, Yue S, Wang W et al (2021) Potential role of gut microbiota in traditional chinese medicine against COVID-19. Am J Chin Med 49(4):785–803. https://doi.org/10.1142/S0192415X21500373
Ethics approval and consent to participate
Consent for publication
The authors have no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
About this article
Cite this article
Nasir Ahmed, M., Hughes, K. Role of ethno-phytomedicine knowledge in healthcare of COVID-19: advances in traditional phytomedicine perspective. Beni-Suef Univ J Basic Appl Sci 11, 96 (2022). https://doi.org/10.1186/s43088-022-00277-1
- Traditional medicine
- Medicinal plants
- Gut microbiome