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Table of Contents
REVIEW ARTICLES
Year : 2020  |  Volume : 8  |  Issue : 2  |  Page : 71-83

Prophylaxis and treatment aspect of COVID-19 with the use of Indian traditional plant-based medicine: A hypothetical review


1 Department of Pharmacognosy, Bhagwan Mahavir College of Pharmacy, Gujarat Technological University, Surat, India
2 Department of Pharmacognosy, B.K. Mody Govt. Pharmacy College, Gujarat Technological University, Rajkot, Gujarat, India

Date of Submission10-Jun-2020
Date of Decision18-Jun-2020
Date of Acceptance25-Jun-2020
Date of Web Publication07-Sep-2020

Correspondence Address:
Mr. Rakeshkumar P Prajapati
Department of Pharmacognosy, Bhagwan Mahavir College of Pharmacy, Gujarat Technological University, Surat, Gujarat.
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JISM.JISM_49_20

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  Abstract 

HCoV (human coronavirus) is a retrovirus containing an enveloped virus belongs to Coronaviridae family. Coronavirus (CoV) family is composed of numerous viral strains and responsible for the cause of common cold, breathing problem, and fever. The chronic CoV infection may cause pneumonia and severe acute respiratory syndrome coronavirus (SARS-CoV) in human beings. The known strains of HCoV are HCoV-OC-43, -229E, and -HKU1. The more extensively known strain is SARS-CoV which caused a worldwide threat with the sky-scraping number of deaths with high mortality rate in 2003. In the year of 2012, the World Health Organization (WHO) nominated a sixth type of HCoV infection recognized as Middle East respiratory syndrome coronavirus (MERS-CoV) which affected Middle East region of the world and showed a high fatality rate. In a similar way, currently coronavirus disease-2019 (COVID-19) has been pandemic and fatal worldwide, which has been originated at China during December 2019. At present, there is no vaccine or treatment to cure COVID-19 infection. In such a time, the pharmaceuticals should promote and encourage natural product drug discovery programs. They should inspire the academic organizations to perform committed research activities to develop natural and alternative therapeutics. Till the date numbers of Indian traditional plants have been reported showing their antiviral potential, immunemodulating potential, and respiroprotective effects. In this review, such kinds of potent antiviral traditional plants are listed and described in very detailed manner along with their active phytoconstituents as well as mechanism of actions. In the current pandemic situation of COVID-19, these traditional plants can be a rich source to develop and design novel natural medicines, therapies, or vaccines against HCoV-2.

Keywords: Coronavirus disease-2019, Coronaviridae, human coronavirus, Middle East respiratory syndrome coronavirus, novel natural medicines


How to cite this article:
Prajapati RP, Kalariya MV, Solanki N, Sanghani G, Jain V. Prophylaxis and treatment aspect of COVID-19 with the use of Indian traditional plant-based medicine: A hypothetical review. J Indian Sys Medicine 2020;8:71-83

How to cite this URL:
Prajapati RP, Kalariya MV, Solanki N, Sanghani G, Jain V. Prophylaxis and treatment aspect of COVID-19 with the use of Indian traditional plant-based medicine: A hypothetical review. J Indian Sys Medicine [serial online] 2020 [cited 2020 Sep 24];8:71-83. Available from: http://www.joinsysmed.com/text.asp?2020/8/2/71/294435




  Key Messages: Top


  • COVID-19 is a fatal epidemic disease caused by SARS-HCoV-2. Nowadays, it gets pandemic worldwide.


  • At present, there is neither available treatment to cure COVID nor any vaccine to prevent it.


  • This review emphasizes on Ayurvedic natural therapy for the management of this disease, with the use of antiviral potential containing Indian traditional plants and medicines derived from them. Such traditional medicines may offer a rich resource for novel antiviral drug development, whereas in silico screening will facilitate various chemical combinations to be investigated for novel drug designing and development.



  •   Introduction Top


    The traditional and folklore systems of medicines have constantly played a very significant role in fulfilling the universal healthcare needs and desires. These systems are enduring to do so at present and also will play a key function in future prospect. Complementary and alternative medicines always propose a huge variety of herbs, which can solve numerous mysteries behind human pathologies. World Health Organization (WHO) reports that almost 80% of the total world’s population in developing countries relies on use of traditional plants and conventional therapies for their healthcare complications. The system of medicine which is believed to be an Indian in origin or the system of medicine, which reached to India from some other countries and assimilated in culture of India, is known as Indian System of Medicine. India has the exceptional peculiarity of having total six acknowledged systems of medicine in this category, which are Ayurveda, Siddha, Unani, Yoga, Naturopathy, and Homoeopathy.[1]

    Among them Ayurveda has legendary journey in Indian history. To promote Ayurvedic practice, a substantial research on pharmacognosy, ethnobotany, phytochemistry, ethnopharmacology, and clinical therapeutics has been carried out on Indian traditional plants. The existing modern system of medicine, Allopathy has progressively come across a picture over the years by observational efforts of scientists. However, the root of its development remains embedded in traditional medicine and natural therapies.[2]

    Traditional plants have been continuing to play a dominant role in improving health and quality to human life since long and have offered humans expensive plant-derived components such as beverages, cosmetics, and dyes. In recent times, the recognition of herbal medicine is merely depended on the natural chemical substances present in the herbal plant, which can maintain health and alleviate illness from the human body. With this background, the research activities on traditional plants have been amplified all over the world. Such kinds of researches have confirmed the enormous potential of medicinal plants used in various traditional systems. Herbal plants and their active phytochemicals have proven useful in the treatment of infectious and contagious conditions and were found as the only remedies accessible, till the discovery of antibiotics. Among these infectious diseases, particularly viral infections were observed as the principal cause of death in humans globally. A number of phytoconstituents obtained from several medicinal plants have been comprehensively investigated for antiviral activity. Based on this principle, an online search tools and operations were designed, which can be useful to identify a huge number of plant species containing the potent antiviral phytocompounds. Such kind of herbal remedies have been reported independently, in combinations or in a group across a vast number of citations studied. The ethnopharmacological investigations on such traditional plants and their phytochemicals always provide a big platform to investigators to satisfy their research desires throughout the world.[3]

    Viruses are the living chemicals accountable for a massive number of pathological complications together with cancer, whereas complex syndromes such as Alzheimer’s disease, herpes, and diabetes. have been also linked with viral infections. Furthermore, due to increased intercontinental journey and fast urbanization, pandemic outbreaks caused by budding, mutating, and re-budding viral strains characterize a severe threat to community health, predominantly when precautionary vaccines and antiviral treatments are not available. Many viral strains remain without efficient vaccination and very few antiviral agents are qualified for therapeutic and clinical practice till the date.

    Coronavirus disease-2019 (COVID-19) is recognized as an infectious condition caused by severe acute respiratory syndrome coronavirus 2 (SARS-HCoV-2).[4] First of all this disease was identified in December 2019 at Wuhan, the capital of China’s Hubei province and later on spread worldwide, consequential in the enduring 2019–2020 COVID pandemic.[5] Ordinary preliminary symptoms of COVID-19 infection include cough, sneezing, fever, and shortness of breath.[6] Other secondary symptoms may comprise fatigue, body ache, diarrhea, sore throat, and digestion complications.[7] The incubation period of HCoV 2 infection is characteristically approximately 5 days but may range from 2 to 15 days.[8] Although the most of the cases result in mild symptoms, but some progress more severe complications leading to pneumonia and other respiratory problems.[9] As on the date of April 27, 2020, approximately 3.04 million cases have been reported across 185 countries and territories, resulting in more than 2, 11, 000 deaths. Although more than 8,94,000 people have been recovered too.[10]

    Survey of literature suggests that considerable number of herbal plants, their phytochemicals, and their preparations naturally exist with antiviral potential against various types of viral strains. Most of such antiviral herbal plants contain bioactive components such as polyphenols, flavonoids, alkaloids, and volatile principles, which play a crucial role against viral infections. Therefore, there is the sky-scraping and urgent need to discover, investigate, and develop novel herbal remedies or antiviral agents to combat COVID-19.

    This review emphasizes the antiviral activities from several potent Indian folklore plants and herbal medicines derived from them. These natural medicines and their derived products can offer a rich resource for novel antiviral drug development, whereas in silico screening will facilitate more and more chemical combinations to be investigated with a nonclinical and randomized clinical trial, making drug development faster, cheaper, and safer.


      Possible Targets or Mechanisms of Antiviral Traditional Natural Agents Top


    The researches on antiviral herbal plants explored till date nurture the researchers and establish a vast scope to screen comprehensively a huge number of other plant species belonging to the same or other families and genus. In this review, the authors have made an effort is to enlist and describe such kinds of antiviral potential containing plants and their precise antiviral mechanisms with their scientific reports and evidences.

    HCoV predominantly targets on Respiratory tract of humans and its chronic infection may destroy all the alveolar pneumocytes of the lungs and so may prove fatal for the entire human population. Its target and transmission are found similar to respiratory syncytial viruses (RSVs). Literature indicates that a noticeable number of phytomolecules from various traditional plants have been investigated against RSVs. Therefore, same plants can be effective against HCoV symptoms too. Another reported mechanism of antiviral activity against HCoV infection is by inhibiting viral attachment, penetration, and invasion cascade by interferon (IFN) production and stimulation.[11],[12]

    Numbers of early investigations showed that several phytoconstituents along with IFNs potentiates the antiviral actions. The combinations of IFN-β and glycyrrhizin, a saponin from Liquorice rhizome have been shown eliciting significant antiviral actions against coronavirus. Therefore stimulation of IFN-α and IFN-β expression is very imperative in prohibiting viral infections and developing resistance to host cells against viruses. This indicates the need for further investigation of the immunomodulation signaling pathways by various phytoconstituents per se or through a combined system in the form of plant extracts and their preparations in a virus-induced pathological condition. The perception of immunomodulation by traditional plants has been subjugated in vaccine discovery technology also, through reports emphasizing the immunemodulating potential of the extracts of traditional plants in combination with vaccines against viral infections.[13]

    Moreover another important group of plants showing antiviral action against multiple viruses available, clearly focusing on the multidisciplinary action of these phytochemicals. With that background, it will be quite appropriate to draw attention to certain traditional plant extracts and their phytocompounds, which originally had been linked for a different pathological situation altogether, but finally, did show convinced antiviral properties also. The phytoconstituents show quite diverse phytochemistry, yet work in synchronization to set up back the Homeostasis state lost during a pathological infection, thus diverting our interest to the holistic approach of therapy with the use of traditional herbal medicines.

    A thorough investigation of traditional plants and their derived formulations along with a bio-activity guided separation of therapeutically active phytocompounds can utterly give a better scheme with reference to the bioactive principles responsible for a varied antiviral action. Experiments and researches in this area are in advancement as collated from different research publications and literatures.


      Clinical Reports: Use of Indian Traditional Plants Showing Potent Antiviral Activity with Precise Mechanism Top


    Fig Fruit/Anjir (Ficus carica Linn.)

    Ficus carica is an Asian species of angiospermic flowering plant belongs to Moraceae family (Mulberry family). It is commonly known as fig tree. Fig fruit was traditionally used for the cure of dermatological infections and possible viral transmitted diseases.

    Houda et al.[14] investigated antiviral potential of the fig fruits. In their study, total five different extracts (methanol, hexane, ethyl acetate, hexane-ethyl acetate (v/v), and chloroform) of the air-dried fruits and evaluated them for their in vitro antiviral activity against herpes simplex type 1 (HSV-1), echovirus type 11 (ECV-11), and adenovirus (ADV). They determined the capacity of the extracts to inhibit viral replication. The antiviral assays were performed by the parameters such as inhibition of adsorption and penetration; intracellular inhibition and virucidal potential. Results of cytopathic effects were used to determine the antiviral potential. The results indicated that the hexane and hexane-ethyl acetate (v/v) extracts inhibited viral replication and multiplication by tested techniques at concentrations of 78mg/mL. Moreover, none of the tested extracts showed any toxic effect on Vero cells.

    The study suggests that Ficus carica fruits show the antiviral activity due to its chief active phytocontituents [Figure 1] such as 5-O-caffeoylquinic acids, ferulic acid; coumarins such as bergapten and psoralen; flavonoids such as quercetin-3-O-glucoside and quercetin-3-O-rutinoside. Moreover, the plant is also known for its elevated confrontation to stress conditions and high therapeutic value. So phytochemicals of the Ficus fruits can be an effective leading compound to target COVID infection.
    Figure 1: Antiviral phytoconstituents of Ficus carica

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    Buckwheat/Kuttu (Fagopyrum esculentum Moench.)

    Fagopyrum esculentum is an annual crop plant belongs to family Polygonaceae and widely grows in North India. For long time cultivation of buckwheat was declined, but recent interest and demand in traditional food products have led to recurrence in its cultivation and collection. At present, it is believed as the most significant alternative crop source and a valuable raw material for preparation of functional foods and nutraceuticals. It is a rich source of starch and many other important nutritive compounds, such as proteins, dietary fibers, antioxidants, and trace minerals. Proteins of buckwheat have unique amino acids composition, which have beneficial pharmacological activities.[15]

    Li and Zhang evaluated buckwheat seeds for their pharmacological actions. Results of their study showed that the seeds showed significant blood cholesterol-lowering effect, antidiabetic effect, and anti-inflammatory effect as well. The buckwheat seeds also reported to show antiviral action by suppression of viral replication by inhibiting reverse transcriptase enzyme. Further the bioactive constituents [Figure 2] such as fagoyrin (naphthodianthrone derivative) and flavonoids viz., rutin, and quercitrin were isolated from the seeds and proved responsible for their pharmacological properties.[16]
    Figure 2: Active phytoconstituents of Fagopyrum esculentum

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    Pomegranate Fruit (Punica granatum Linn.)

    Punica granatum is a flowering deciduous shrub in the family Lythraceae, subfamily Punicoideae, which is 5–8 m tall in height and mainly found in the Himalayan territory and in the northern region of India.

    Houston et al.[17] evaluated antiviral potential of Punica granatum fruit rinds against Herpes Simplex Virus-1 (HSV-1) in 2017. In the study they prepared the extract of pomegranate fruit rinds and administered along with zinc salts. They determined virucidal assays and antiviral effects on epithelial Vero cells. MTS assay was conducted to determine the cytotoxic effects with the help of commercial kit. Zinc salts such as zinc sulfate, zinc citrate, zinc stearate, and zinc gluconate showed similar elevated virucidal action with the fruit rind extract against HSV-1 by extent up to fourfolds. Along with the varying concentrations of zinc sulfate, the fruit rind extract showed the highest potentiation factor of 5.5. Punicalagin [Figure 3], a potent phytocompound of the pomegranate fruits had eightfold higher virucidal activities than an equal mass of the fruit rind extract. Punicalagin significantly reduced antiviral activity even compared to the rind extract (EC50 = 0.56 μg/mL), a value comparable to standard antiviral drug aciclovir (EC50 = 0.18 μg/mL). Moreover, no cytotoxic sign was observed with any test drug.
    Figure 3: Punicalagin: an active antiviral phytoconstituent of Punica granatum

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    Thus the antiviral activity of pomegranate fruits has noticeable potential as a novel curative agent against HSV and other viral infections.

    Ginseng/Man Root (Panax ginseng Mey.)

    Panax ginseng is fleshy roots containing perennial plant, belonging to family Araliaceae. In India, it is grown commercially in Himachal Pradesh, Tripura, Uttarakhand, and Maharashtra. Traditionally this plant has been known as a potent immunomodulator drug.

    Lee et al.[18] investigated ginseng (Korean red species) root extract for evaluation of antiviral effects on RSV infection through in vitro and in vivo assays. The results of the study showed that the root extract improved the survival of pneumocytes of lungs against RSV infection by inhibiting viral replication. In addition, the root extract suppressed the expression of inflammatory cytokine genes (IL-6 and IL-8) and the production of reactive oxygen species in pneumocyte cultures. In addition, the in vivo effects of the ginseng extract showed an elevated level of IFN-γ by producing dendritic cells subsequent to RSV infection. Thus, this study concludes that the consumption of ginseng may show favorable effects in the prophylaxis and treatment of RSV infection.

    Bitter glycosides, panaxosides, and ginsenosides were found to be present as bioactive phytocompounds in ginseng root [Figure 4]. However, the accurate possible underlying antiviral mechanism of ginseng and its constituents are yet to be discovered.
    Figure 4: Active antiviral glycosides of Panax ginseng

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    Plum Fruit (Prunus domestica Linn.)

    Prunus domestica, commonly referred to as plum, is a species of flowering plants belonging to Rosaceae family and usually found in the semi-arid Environment of North-West India.

    Bose et al.[19] evaluated fruits of Prunus domestica for its antiviral potential against infection of hepatitis C virus (HCV). The results of the study showed that the fruits significantly inhibited HCV entry and revealed its hepatoprotective effects. Further they isolated and identified flavonoid, rutin [Figure 5], as bioactive phytocompound present in the fruits. They reported that rutin, as bioactive compound of plum fruit, inhibited HCV-LP binding to hepatoma cells. Rutin also significantly inhibited cell-culture derived HCV (HCVcc) entry into hepatoma cells. In addition, it was found to be quite safe to hepatoma cells without inducing any toxicity sign.
    Figure 5: Active antiviral phytochemicals of Prunus domestica

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    In addition to this, the phenolic compounds [Figure 5] such as gallic acid and chlorogenic acid were also isolated and showed as active phyochemicals of the plum fruits. Thus, plum fruits and their active phytocompounds may be dominant source for the development of natural therapeutic agents against HCoV 2 in the management of COVID-19.

    Garlic Bud (Allium sativum Linn.)

    Allium sativum is one of the prominent legendary of all plants in history of India. It is an aromatic bulb crop belongs to family Liliaceae (Alliaceae) and grown throughout the country. It has been shown that garlic has various pharmacological properties on a vast number of diseases. It possesses biopotent sulfur containing phytochemicals, that is, alicin, and diallyl disulfide [Figure 6].
    Figure 6: Potent bioactive phytochemicals of Allium sativum

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    Mehrbod et al.[20] investigated antiviral potential of the garlic extract. In the study, Madin-Darbey Canine Kidney (MDCK) cells were treated with minimum effective cytotoxic concentration of the garlic extract and 100 TCID50 (50% Tissue Culture Infectious Dose) of the virus during infection at different time intervals. To determine the viral titers hemagglutination (HA) and TCID50 bio-assays were performed. The antiviral action of the extract was investigated at 1, 8, and 24h after treatment on the culture. For the measurement of the amount of viral genome developed at different times after treatment, RNA extraction, reverse transcription-polymerase chain reaction (RT-PCR) and free band densitometry software were performed for evaluation. The results of the study showed the antiviral potential of garlic and concluded that the bioactive compounds present in the garlic extract reacted with thiol groups of the enzymes such as alcohol dehydrogenase and thioredoxin reductase and inactivated them.

    This study indicates that the garlic extract shows high selectivity index with inhibitory effects on the penetration and proliferation of virus in cell culture. However, further research is needed to isolate its active phytochemicals and to find out their precise mechanism responsible for its antiviral action.

    Kalmegh Root/Green Chirata [Andrographis paniculata (Burm.) Nees]

    Andrographis paniculata is called as Kalmegh, King of Bitter of India. From ancient period of time the stems of this plant have been used for its predominant hapatoprotective action. It is an annual herb belonging to Acanthaceae family. It is indigenous to India and Sri Lanka. Andrographolide [Figure 7], a diterpenoid derived bitter glycoside, is a chief potent phytoconstituent of this plant.
    Figure 7: Andrographolide: the antiviral bitter phytocompound of Andrographis paniculata

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    Gupta et al.[21] investigated antiviral properties of andrographolide against various viral infections. The results of the study showed that andrographolide suppressed the viral genome replication by promoting production of IFN-α. It also inhibited viral HO-1 gene expression and viral NS3/4A protease activity. Moreover, andrographolide also showed positive effects on immunomodulation by increasing the production of cytotoxic T cells, natural killer (NK) T cells, histocytes, and antibody-dependent cell-mediated cytotoxicity (ADCC).

    Mulethi/Liquorice Rhizome (Glycyrrhiza glabra Linn.)

    Glycyrrhiza glbra is a flowering plant of the bean family Fabaceae and commonly known as Mulethi. It is a perennial leguminous herb indigenous to the Western Asia and Southern Europe. Glycyrrhizin [Figure 8], a saponin glycoside is the chief phytocompound of this plant.
    Figure 8: Bioactive saponin glycosides of Glycyrrhiza glbra

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    Cinatl et al. reported that glycyrrhizin showed significant antiviral action by inhibiting viral replication. During the study, it was reported that EC50 value for glycyrrhizin was 316–625mg/L, which was added two times during the incubation time period of 7 days. The study concluded that glycyrrhizin showed antiviral potential via inducing production of IFN-α/ β and also showed immunomodulating property.[13],[22]

    However, the precise mode of glycyrrhizin’s antiviral action against HCoV is uncertain yet. It is hypothesized that glycyrrhizin influences cellular signaling pathways of various enzymes such as protein kinase C and casein kinase II. It activates transcription factors such as activator protein 1 and nuclear factor as well. Furthermore glycyrrhizin and its aglycone moiety, glycyrrhetinic acid, upregulate the expression of nitrous oxide synthatase and production of nitrous oxide in macrophages. The report indicated that nitrous oxide inhibits replication of several viral strains

    Ephedra/Ma Huang Stem (Ephedra sinica Stapf.)

    Ephedra sinica is a gymnospermic plant native to Asia belongs to family Ephedraceae. Ephedra has long been considered as a potent traditional plant for the cure of viral infections of the respiratory tract such as influenza, bronchitis, and asthma.

    Wei et al.[23] investigated ephedra stem for the screening of antiviral potential. The results of the study showed that among nine major alkaloidal principles of ephedra stem, L-methyl ephedrine (LMEP), L-ephedrine (LEP), and D-pseudoephedrine (DPEP) [Figure 9] inhibited the proliferation of influenza A virus in vitro in very significant manner. It was observed that the inhibitory effect at 24hr after the treatment was more apparent than that at 48hr. They also inhibited the genes relevant to mRNA expression cascade pathways such as toll-like receptor (TLR3), TLR4, and TLR7 signaling pathways, which were accompanied by the downregulation of Tumor Necrosis factor-α (TNF-α) level and the upregulation of IFN-β level in the cell supernatant. Thus the ephedra alkaloids inhibited viral replication and modulated inflammatory response and so showed the antiviral effect in vitro. Further, the clinical investigations showed that LEP and DPEP significantly relieved lung injury and virus load in the pneumocytes of lungs. LEP and DPEP also inhibited the mRNA expression levels of TNF-α, TLR3, TLR4, TLR7, MyD88, NF-κB p65, and RIG-1 as well as the protein expression levels of TLR4, TLR7, MyD88, and NF-κB p65 and markedly increased thymus index, the level of IL-10 in serum and the expression level of IFN-γ. LEP and DPEP had shown protective effects on the influenza virus-infected mice, which may be associated with their abilities of effectively healing lung injury, improving the immunoglobulin level in infected mice. The overall study confirmed that the ephedra alkaloids have high potential as antiviral agents, as effective and inexpensive natural substances.
    Figure 9: Antiviral alkaloidal principles of Ephedra sinica

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    Dalchini Bark [Cinnamomum cassia (L.) D.Don]

    Cinnamomum cassia is the dried bark of a small bushy evergreen tree belongs to family Lauraceae. In India, it is grown in North Eastern States and in the evergreen tracts along the high ranges of the Western Ghats. It is a very popular traditional remedy due to its active volatile principles.

    Literature shows that Cinnamomum cassia shows the antiviral property. Fatima et al.[24] formulated silver nanoparticles with the help of cinnamon bark and evaluated them against highly pathogenic avian influenza virus subtype H7N3. They used ultraviolet–visible (UV–Visible) absorption spectroscopy, scanning electron microscopy, and Fourier transforms infrared spectroscopy (FT-IR) to characterize the synthesized nanoparticles. Cinnamon bark extract and its nanoparticles were tested against H7N3 influenza A virus in Vero cells. The cell viability was determined by dimethyl thiazol-2-diphenyl tetrazolium bromide (MTT) assay. The results showed that the silver nanoparticles formulated from cinnamon bark extract showed the antiviral potential and were found to be effective in prophylaxis and treatment. Further, the cinnamon bark extract and its nanoparticles were evaluated for their cytotoxic effects in Vero cells to determine its safety profile, in which they were found nontoxic to Vero cells up to a concentration of 500 μg/mL.

    Therefore the cinnamon bark nanoparticles can be a hopeful remedy for the treatment against various viral infections. Phytochemical investigations reveal the presence of volatile principles [Figure 10] such as cinnamaldehyde, cinnamyl acetate, and cinnamic acid in the cinnamon bark, as the therapeutically active compounds. Thus this study encourages the development of traditional medicine-based novel drug delivery system to target COVID-19.
    Figure 10: Therapeutically active volatile principles of Cinnamomum cassia

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    Simdalu/Fishwort/Chameleon Plant (Houttuynia cordata Thunb.)

    Ethnobotanically Houttuynia cordata is an important plant of Northeastern region of India, belongs to family Saururaceae. It was selected by microbiologists to tackle HCoV responsible for SARS problem as it was traditionally used for the treatment of pneumonia and other lung disorders.

    Lau et al.[25] investigated the immunological and antiviral potential of the plant against SARS-virus. Results of the study showed that aqueous extract of Houttuynia stimulated the proliferation of mouse splenic lymphocytes in a significant and dose-dependent manner. It was observed that the extract raised the proportion of CD4+ and CD8+ T cells in the assay of flow cytometry. Moreover, the extract significantly promoted the secretion of IL-2 and IL-10 by mouse splenic lymphocytes. In antiviral assay, the plant extract showed significant inhibitory effects on 3C-like protease (3CLpro) and RNA-dependent RNA polymerase. The reports of oral acute toxicity study revealed that Houttuynia was safe to experimental animals following oral administration at 16 g/kg body weight. Phytochemical studies on the plant suggested the presence of Houttuyin and Caffiec acid as bioactive phytoconstituents [Figure 11]. Thus the results of this study provided scientific data and evidence to support the competent and safe use of Houttuynia plant and its phytoconstituents to combat HCoV 2 infection.
    Figure 11: Pharmacologically active volatile principles of Houttuynia cordata

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    Indian Indigo (Isatis indigotica Fort.)

    Isatis indigotica, usually known as Asp of Jerusalem, is a flowering plant in the family Brassicaceae. This plant is indigenous to Southern Asia.

    Lin et al.[26] showed the antiviral action of Isatis indigotica against SARS-CoV. In this study, the indigo root extract and its major phytocompounds [Figure 12] aloe-emodin and hesperetin examined for anti-SARS-CoV action with the help of cell free and cell-based cleavage microbiological assays. The cleavage assays with the 3CLpro showed that the root extract and its phytocompounds showed an antiviral effect in a significant manner. The report of cell-based assay indicated that aloe-emodin and hesperetin dose-dependently inhibited cleavage activity of the 3CLpro in a dose-dependent manner. The IC50 value of aloe-emodin and hesperetin were 366 μM and 8.3 μM, respectively.
    Figure 12: Antiviral active phytochemicals of Isatis indigotica

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    This study evident the antiviral effect of the roots of Isatis indigotica, particularly against CoV and so this plant can also be recognized as a promising therapy for COVID-19.

    Katira/Milk Vetch (Astragalus membranaceus (Fisch.) Bunge)

    Astragalus membranaceus is a major traditional medicinal herb that belongs to Fabaceae family. It is primarily found in the temperate region as well as the alpine regions of the Himalayan territory. It has been commonly used in many herbal formulations in the practice of traditional medicine.

    Recently, Khan et al.[27] evaluated the antiviral activity of Astragalus membranaceus root extract against Avian influenza H9 virus. In the study toxicity profile of extract was investigated using chicken embryos and BHK-21 cell line. Different concentrations viz. 3.12, 6.25, 12.5, 25, 50, 100, 200, and 400 μg/mL of both aqueous and methanol extracts of the Astragalus roots were prepared and mixed with standard virus inoculum (4HA units) and incubated at 37°C prior for 30 min to inject the chicken embryos. Chorioallantoic fluid harvested 72h postinoculation and evaluated for virus growth using HA assay. Further, the same concentrations of both extracts without virus were injected in chicken embryos to evaluate embryotoxic activity. The cytotoxic activity of aqueous and methanol extracts was determined by MTT colorimetric assay. Three concentrations (400, 200 and 100 μg/mL) of aqueous and five concentrations (400, 200, 100, 50, and 25 μg/mL) of methanol extract showed antiviral action. None of the tested concentrations of aqueous and methanol plant root extracts caused chicken embryo mortality. Cell survival percentage of aqueous extract was higher than 50 at all of the tested concentrations except 400 μg/mL. Two concentrations (400 and 200 μg/mL) of methanol extract showed cytotoxicity.

    This study reveals that the roots of A. membranaceus show antiviral activity with least side effects and so may be used for the treatment of viral infections such as HCoV 2 infection. Moreover, phytochemical screening of the plant roots indicated the presence of flavonoids such as astragalin and astragaloside, as pharmacologically potent antiviral compounds [Figure 13].
    Figure 13: Pharmacologically active phytochemicals of Astragalus membranaceus

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    Elder Berry (Sambucus Species)

    Sambucus species are group of flower bearing plants belonging to family Adoxaceae. It is indigenous to entire Europe and North America. In India commonly found Sambucus species are Sambucus nigra and Sambucus Canadensis.

    Porter RS and Bode RF 2017 reported antiviral potential of Sambucus species such as Sambucus nigra, Sambucus canadensis, Sambucus ebulus, and Sambucus javanica. In addition to that Lectins were isolated from Sambucus species and proved responsible for its antiviral potential.[28] In addition, phytochemical reports of the plant revealed the presence of bioactive phenolic compounds, Quertin 3-0-glucoside and isorhamnetin [Figure 14].
    Figure 14: Antiviral flavonoids of Sambucus species

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    Moreover Hindol et al.[29] prepared a herbal antiviral formulation of Sambucus plants and investigated them against various viral strains. The authors identified the lectins as potential antiviral phytocompounds present in the plant. Lectins showed antiviral action through prevention of viral penetration to cells by binding to the virions and agglutinating virus particles. In addition, lectins masked the viral receptor sites present on the cell wall.

    Further during clinical trials, this herbal formulation was observed quite safe for daily consumption in both the routes of administrations, oral as well as parenteral.[30] And so with this background elderberry may be promoted as a natural remedy for COVID-19.

    Zaminkand/Yam Tuber (Dioscorea Species)

    Dioscorea is an annual type edible underground tuber. It is widely grown in North-eastern states, West Bengal, Bihar, Odisha, Madhya Pradesh and Uttar Pradesh in India. Recently diosgenin and yamogenin, the chief phytoconstituents of Dioscorea [Figure 15], were reported to show in vitro antiviral activities against hepatitis B virus and vesicular stomatitis virus. However, their effectiveness was variable in different stages of infections.[31]
    Figure 15: Antiviral potent saponins of Dioscorea species

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    Hood et al.[32] prepared the extracts from the tubers of different Dioscorea species such as D. alata L. var. purpurea, D. pseudojaponica and D. ecne. The authors evaluated their antiviral action by in vitro assay. During the study it was observed that dioscorea extracts effectively treated viral infections such as infection by a herpesvirus, a poxvirus, a picornavirus, an ADV, an orthomyxovirus, a paramyxovirus (e.g., RSV), a coronavirus (e.g., SARS), a papovavirus, a hepadnavirus, a flavivirus or a retrovirus. The extracts showed their antiviral effects via acting as antigenic polypeptide, such as a tumor antigen peptides or a nucleic acid encoding the polypeptide. This investigation proved that dioscorea tuber and its preparations can be utilized as a good source of nutraceuticals to prepare dietary supplements, functional foods, or health drinks to boost the immune system and resist viral infections such as HCoV.[33],[34],[35],[36],[37],[38]

    All the above mentioned investigational reports suggest that the enormous number of Indian traditional plants show significant antiviral potential against various viral strains including coronavirus, with exceptionally precise mechanism. Some more of such Indian folklore plants are listed in [Table 1]. Thus these all Indian traditional plants and their bioactive phytochemicals can be the most vital leads to find out novel therapeutic agents for COVID-19, by using in silico methods for drug design and discovery.
    Table 1: List of Indian traditional plants having antiviral potential along with their mechanisms

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      Future Prospect Top


    Reports confirm that the natural medicines derived from Indian traditional plants have contributed a very significant role in the treatment various kinds of viral infections so far. Furthermore, supplementary investigational studies should be carried out to examine the possibility of combination therapeutic treatments with novel natural agents or with standard existing antiviral therapeutic agents, as a multitarget therapy may be beneficial to lessen the risk of generating drug-resistant viral strains. Therefore there is a high need to emphasize on the development of competent therapeutic strategies against viral infections such as COVID-19 based on computational modeling and structure-activity relationships.


      Conclusion Top


    The current epidemic of COVID-19 in the entire world is creating an extensive challenge in the community health sector. Because of lack of precautionary vaccines and efficient antiviral treatments, Diagnosis, abolition, and treatment of viral diseases always appear quite difficult. This review enlists and elaborates several Indian traditional plants; those had appreciably improved symptoms of SARS pandemic and quality of life of human beings. Based on preceding experiences of treating SARS with Indian traditional herbal remedies, Ayurveda and the naturopathy encouraged the research and use of such Indian traditional plants to develop the antiviral remedies against HCoV-2.

    Acknowledgement

    The authors would like to acknowledge all the researchers and contributors, cited in the bibliography, whose investigations helped me a lot to prepare this review article.

    Financial support and sponsorship

    Nil.

    Conflicts of interest

    There are no conflicts of interest.



     
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        Figures

      [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11], [Figure 12], [Figure 13], [Figure 14], [Figure 15]
     
     
        Tables

      [Table 1]



     

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