STRATEGIES OF TRADITIONAL SYSTEMS OF MEDICINE COMBATING WITH THE CURRENT PANDEMIC SITUATION OF COVID-19HTML Full Text
STRATEGIES OF TRADITIONAL SYSTEMS OF MEDICINE COMBATING WITH THE CURRENT PANDEMIC SITUATION OF COVID-19
Deepti Katiyar 1, Priya Bansal 2, Manish 3 and Abhishek Kumar * 2
Division of Pharmacognosy 1, Division of Pharmacology 2, KIET School of Pharmacy, KIET Group of Institutions, Delhi-NCR, Ghaziabad - 201206, Uttar Pradesh, India.
ABES Engineering College 3, Delhi-NCR, Ghaziabad - 201009, Uttar Pradesh, India.
ABSTRACT: Coronavirus disease (COVID-19) has become pandemic in no time in the world. Understanding the pathophysiological similarities with previously known viruses of the class gave opportunities to explore various molecular targets against COVID-19. Vaccines unavailability propose different research approaches of treatment, including various previously known and some new synthetic molecules, which are also associated with many unwanted effects. Phytochemical compounds and formulations also gain interest in this era, and all the traditional medicine systems were analyzed for any probable therapeutic possibilities. Hence author summarize the various approaches of herbal-based medicine against COVID-19 infection. Ayurveda, Siddha, Unani, Homeopathy, and Chinese medicine systems constitute major traditional herbal-based systems known worldwide. Previous literature were studied to recapitulated findings with modern multi-mechanistic approaches and propose the use of herbals against COVID-19. Scientists are identifying all the possible interventions associated with herbal-based systems to have efficacy against various mechanisms against viral infection. Various herbal extracts and formulations are utilized to increase the human body’s immune system to counter the pathophysiological changes due to COVID-19 infections. Promotion of these herbal-based medicines having a positive impact on the immune system is essential now. The review discussed the old and novel approaches revealing the efficacy of different phytoconstituents and herbal-based medicines against COVID-19. This review briefly highlighted the use of traditional herbal-based medicine systems against the novel coronavirus utilizing the modern approaches of multi-mechanistic targeting. A thorough investigation of different formulations from these systems is warranted through clinical studies for their global acceptance.
COVID-19, Traditional system, Herbal-based medicine, Ayurveda
INTRODUCTION: Increased understanding of genetics and virology revealed that similar pathogenicity shared by the three most severe coronavirus species SARS-CoV-2 (COVID-19), SARS (Severe Acute Respiratory Syndrome), and MERS (Middle East Respiratory Syndrome) resulting in similar symptoms profile of fever, cough, headache, fatigue, and shortness of breath that may progress to pneumonia, pulmonary embolism, organ failure, and even death 1, 2.
In addition, novel drug discovery approaches including, homology modeling and virtual screening, applying protein crystallography data to determine molecules of interest against SARS-CoV-23. The available drugs can be screened targeting different proteins involved in coronavirus adherence to human cells, viral replication, and various molecular functions. Viral spike (S) glycoprotein interaction with angiotensin-converting enzyme 2 (ACE-2) in the lung tissue that is resulting in severe inflammation and vascular permeability are well-reported targets for researchers 4. Viral capsid associated proteins like Spike, nucleocapsid (N), envelop (E), and membrane (M) glycoproteins with many accessory proteins comprise the attachment, viral replication, virions maturation, and further infection severity of SARS-CoV-2 5. Researchers have evaluated various flavonoid and non-flavonoid based natural products against viral fusion and interaction with human ACE-2 receptor 6. Previously available antiviral and antimalarial drugs are extensively studied against different viral targets to interfere with viral fusion and replication with promising results. Still, in many cases, the pharmacological limitation of using broad-spectrum antiviral and antimalarial has proven to be ineffective 7, 8. Currently, many targets are under extensive studies resulting in the repurposing of available molecules from natural products. Utilizing virtual screening methods, Vardan and Sahoo have investigated 18 naturally occurring potential ligands and found limonene and other compounds with interactive capacity (docking score-based) against S-protein, ACE-2, and RNA-dependent RNA polymerase 9.
Being a β-coronavirus SARS-CoV-2 on transcription produces large polypeptides which are cleaved by different proteases to produce desired proteins 10. SARS-CoV-2 possesses Papain-like protease (PLpro) and Main protease (Mpro), also known as 3-chymotrypsin-like protease (3CLpro), facilitating the cleavage of polypeptide 11. Small proteins produced by Mpro and PLpro mainly contribute to the generation of RNA polymerase, endoribonuclease, exoribonuclease, and other functional proteins contributing to complicated viral RNA replication and maturation of virus 11-13. Many researchers have screened different herbal extracts and phytochemicals against Mpro and PLpro. Previously, the presence of an apigenin moiety at position C-3' of ﬂavones, as biﬂavone in the leaf extract of Torreya nucifera had a Mpro inhibitory efficacy 13. Further, constituents obtained from fruit extract of Paulownia tomentosa tree are capable of targeting PLpro 11. Chandel and coworkers screened 19 phytoconstituents against Mpro and revealed an inhibitory potential and best ADME properties in Rhein, Withanolide D, Withaferin A, Enoxacin, and Aloe-emodin 14.
Coronaviruses are large enveloped viruses with RNA as genetic material. In addition to all probable targets discussed above, drug targeting to the RNA replication is a potential drug development approach. RNA-dependent RNA polymerase (RNAp) is an essential enzyme for viral replication 15. Targeting RNAp can bring vital changes that hinder the replication of RNA from RNA template (transcription) in CoV-2 virulence 16. Earlier, various RNAp inhibitors are developed as successful antiviral candidates against RNA viruses 17, 18.
Researchers utilized virtual screening tools to investigate various phytochemicals from traditional Chinese medicines and reported potency of theaflavin, quercetin and kaempferol against RNAp and proposed for further antiviral evaluation of these compounds counter to CoV-216, 19-21. Targeting RNA replication may interfere with virion assembly formation and further viral release. Like RNAp, viral helicase (a non-structural protein) is also an important component of RNA replication 22. Sensing the need of this era, the curiosity of researchers, new drug approaches are implemented utilizing available knowledge to explore drugs that can control the SARS-CoV-2 infection to control pandemic conditions until a vaccine can be made available.
Further, studies have suggested herbal medicines as sources of a suitable new drug or feasible alternatives to resistant-viable drugs against viral disease 23. Emphasizing the prevention of previous viral infections of SARS, other viral diseases, Chinese herbal medicines were suggested as an auxiliary approach against SARS-CoV-2 24. Ang and coworkers evaluated 28 traditional herbal formulations to be used against CoV-19 on the basis of available guidelines. They revealed that Glycyrrhizae Radix et Rhizoma, Armeniacae Semen Amarum, ephedrae Herba, and Gypsum Fibrosum are mostly used in these guidelines1. Various studies suggested the lacking of clinical evidence to warrant the efﬁcacy of traditional medicine. The Indian traditional system of medicine (Ayurveda and Siddha), the Unani medicine, and the Chinese herbal medicine system provide herbal preparations effective against various ailments, including viral infections 25, 26. Phytoconstituents specified in the literature are identified and evaluated for efficacy against various infectious diseases 27. Further, many treatment formulas and protocols based on Chinese herbal medicines are also investigated for preventive and curative measures against CoV-2 infection 27, 28. More trial-based evidence is required for these herbal-based preparations and specific phyto-constituents to make them globally accepted. In this review, we summarized the molecular aspects of phytoconstituents and traditional medicinal systems to evident their efficacy against molecular targets of CoV-2. The phytoconstituents are proposed with promising antiviral activity through variable mechanisms and are recommended further for preclinical and clinical studies for their safe and effective use in clinical practices.
Methodology: The literature of traditional medicine is as old as human civilization. But pharmaceutical advances and scientific evidence are available since about two centuries. Authentic and reputed scientific search engines including Web of Science (https://webofknowledge.com), Google Scholar (https://scholar.google.com/), Pubmed Central (https://www.ncbi.nlm.nih.gov/ pmc/), Medline (https://www.nlm.nih.gov/), Scopus (https://www.scopus.com), and Science Direct (https://www.sciencedirect.com), were utilized for detailed literature survey.
A detailed bibliographic search was performed using these databases on different traditional medicine systems and all the approaches against viral infections. The literature survey includes published books, reports, conference proceedings, and articles in peer-reviewed journals from 1991 till 2020 that include reports of texts available on traditional medicines from many decades. After assessment of more than 200 literatures a total of 91 full-text references were included in this manuscript to summarize the correlation of phyto-constituents and herbal-based medicine systems with severe viral infections, including COVID-19.
Various interventions of traditional medicine systems and newer approaches of modern pharmacology are reviewed to explore the multi-mechanistic approaches of phytoconstituents against COVID-19 infection. Although the literature on herbal-based medicines and their antiviral efficacy is wide evidence but we tried to conclude the important implications related to combating COVID-19 conditions.
Strategies Adopted by Traditional Systems of Medicines against Covid-19:
3.1 Ayurvedic System of Medicine: Ayurveda mentions the concept of epidemics under the term of Janapadodhwamsa 30, explaining that some disruption in the balance between Vayu (Air), Jala (water), Desha (habitat), and Kala (seasons) results in such diseases which kill mass of people. Thus, the Ayurvedic interventions have been explored for the prophylaxis, treatment, and management of COVID-19 31, 32.
The Ministry of AYUSH, Government of India, has issued the guidelines for enhancing the immune system to combat the pandemic viral disease, which includes preventive health manoeuvre like general measures (drinking warm water; practicing yogasanas; adding spices like turmeric, coriander, cumin, and garlic while cooking food); ayurvedic immunity promoting measures (taking 1tsf of Chyavanprash in the morning; drinking herbal tea made from Tulsi (Basil), Dalchini (Cinnamon), Kalimirch (Black pepper), Shunthi (Dry Ginger) and Munakka (Raisin) - once or twice a daily and golden milk); Simple Ayurvedic procedures (Nasal application and oil pulling therapy) and steps to be taken during dry cough/sore throat (Steam inhalation with Pudina (Mint) leaves or Ajwain (Caraway seeds) and Lavang (Clove) powder with honey) 33. In addition to these guidelines, an expedient and tenable action plan for Ayurvedic involution has been presented for people under the following four categories 32:
(1) Unexposed Asymptomatic Group: This group includes basically the healthy people who neither exhibit any type of symptoms nor have any associated risk factor, and they are most appropriate for strengthening the immune system.
Here the pharmacological and non-pharmacological approaches are included as precautionary measures. A healthy lifestyle, adequate sleep, ample of physical activity, care of suppressible and insuppressible impulses, sadvritta (equilibrium between body, mind, social and spiritual well-being) and social distancing from the infected persons is important 34.
(2) Exposed asymptomatic (Quarantined): The Quarantined group consists of such people which do not manifest any symptoms but have a contact history. These can be prevented from the infection by giving Sanjeevani vati (consisting of 10% each of Embelia ribes, Acorus calamus, Tinospora cordifolia, Semecarpus anacardium and Aconitum ferox widely used in fever due to infection and also in communicable diseases) 35 and Chitrakadivati (consisting of 6.66% each of Plumbago zeylanichum, Apium graveolens, Piper nigrum and Piper chaba) and a blend of Guduchi (Tinospora cordifolia), Haridra (Curcuma longa) and Shunthi (Zingiber officinale). This option targets to conserve the agni and aam pachana so that the progress of pathogenesis can be stopped in its primary sanchayaprakopa-prasara stage 36. This group may also be administered with decoction containing some antivirals and broad-spectrum protease inhibitors like Zingiber officinale, Curcum alonga, Tinospora cordifolia, Ocimum sanctum, Adhatoda vasica, Glycyrrhiza glabra, Swertia chirata, Andrographis paniculata, Moringa oleifera, Trikatu (composed of dried Zingiber officinale, Piper nigrum and Piper longum) and Triphala (composed of Emblica officinalis, Terminalia bellerica, Terminalia chebula) 37-39.
(3) With Mild COVID-19 symptoms: This group includes SARSCoV-2 positive people exhibiting mild Upper Respiratory Tract Infection. They should be cautiously isolated and observed for any progress of the disease. An adequate therapy should be given to them in order to stop the symptoms and balance the disturbed doshas. Ayurvedic formulations such as Lakshmi Vilas Rasa 40, Sanjeevani vati 35, Pippali rasayana 41, Chitrakadi vati, Vyaghri haritaki, Gojihvaadi kashaya, Kantakaari avaleha, Talishadi, Dashamulkwath, Sitopaladi 42 and Yashtimadhu may be administered to patients in this stage. Those patients exhibiting the progression of infection may be quickly shifted to ICU 25.
(4) With Moderate to Severe COVID-19 Symptoms: This group consists of patients with high risk. Along with tertiary care, the victims can be given Ayurvedic medicines to decrease the impact of pathology and secure more time for intensive control 43, Pippali rasayana 41, Sanjeevanivati, Laghu Vasant Malati, Tribhuvan keerti rasa 44, Mrityunjaya rasa, Brihata Vata Chintamni rasa, and Siddha Makardhvajarasa are few of the Ayurvedic formulation which can be given during this stage. The Rasaaushadi show enhanced bioavailability due to the nanosize of their particles 45.
Besides the above plan, the Ayurveda professionals should be properly trained for screening the people for associated risk factors. They should also be provided with modern personal protection equipment and access to diagnostic facilities. Good networking of AYUSH healthcare authorities with local health authorities may help effective utilization of human resources in the AYUSH community during the current crisis 46.
3.2 Unani System of Medicine: The Unani System of Medicine refers to an epidemic as waba, which is thought to occur if such contagion or ajsam-i-khabitha find a place in air or water 47. It has also been stated that most epidemics develop in autumn season, especially if the preceding summer season was humid and the wind is still 48. Ibn Sina (980–1035 CE) stated, “epidemics spread from one person to another, and one city to another like a message” 47. Zakariya Razi (865–925 CE) stressed this fact and stated, “there will always be something common in patients of epidemics, whether a place, food, drink or travel history” 49. Thus, these Unani practitioners stressed on the fact that the transmission occurs through fomites. Although the microbial studies are not mentioned in this traditional system of medicine yet the Unani scholars could imagine and understand the concept of microorganisms transmitting the infections and transforming into epidemics 50.
Apart from isolation and quarantine, the epidemic management in Unani medicine includes the following measures:
(i) Sanitization of Surroundings: During the epidemic, the sanitization of the surroundings is very important because it is the channel that eases the spread of infection. The Unani texts mention the usage of medicinal herbs as decoction or distillate for spray (e.g., vinegar from sugarcane, Saccharum officinarum) or as fumigants (e.g., sandalwood - Santalum album and camphor - Cinnamomum camphora) to make the air free from impurities 50. Zakariya Razi enlists the aromatic drugs used as fumigants during epidemics such as, loban (Styrax benzoides, mastagi (Pistacia lentiscus), izkhar (Cymbopogon jwarancusa, zanjabeel (Zingiber ofﬁcinale), sibr (Aloe vera), and za'fran (Crocus sativus) 49. There is not much scientific data revealing the use of volatile oils as fumigants. The theory behind using essential oils for this purpose might be their antimicrobial potential due to their alcoholic content 51.
(ii) Dietary Modifications: During the situation of epidemics, it is advisable not to eat meat, sweets, and fruits with higher water content. Fish should be avoided entirely. The meat of birds found on the mountain may be consumed.
The reason being that the animals staying on land or water are more likely to be infected than those found at higher altitudes. Intake of citrus fruits such as lemon, oranges, and grapes is advisable. Oxymel (a mixture of honey and vinegar) containing Arq-e-gulab (rose water) has been suggested to provide protection during epidemics 48, 52. Fasting, overeating, and dry throat may cause adverse effects on the bodily constitution 47.
(iii) Health Promoting Herbs: The Unani Practitioners have prescribed single herbs as well as a combination of herbs for the protection of health during an epidemic. The following drugs have been advised:
(a) Antimicrobial drugs like Sirka (Acetic acid-vinegar) 48, 53, Turanjabeen (Alhagi pseudalhagi) 54, Anar (Punica granatum) 52, 55, Revand Chini (Rheum austral) 56, banafsha (Viola odorata) 57.
(b) Immunomodulatory herbs like Amaltas (Cassia ﬁstula) 52, 58, Za’fran (Crocus sativus) 59.
(c) Anti-inflammatory agents such as Toot (Morus nigra) 48, 60, Revand Chini (Rheum austral) (Pandith et al., 2018), Imli (Tamarindus indica) 61.
(d) Antioxidants like Arq-e-Gulab (Rosa damascene) 48, 62, Anar (Punica granatum) 52, 55, Amaltas (Cassia ﬁstula) 58.
(e) Anti-pyretic drug like Turanjabeen (Alhagi pseudalhagi) 54.
(f) For respiratory diseases, a solution of sumaq (Rhus coriaria L., decoction), rub-e-toot (Morus nigra L.), rub-e-jauz (Juglans regia L.), and arq-e-gulab (Rosa damascene) before sleep is advised48.
Considering the above facts, the Unani System of Medicine has summarized the following measures for symptoms of COVID-19, which resemble those of nazla-e-wabaiya mentioned Unani literature:
(a) Preventive Measures: General measures of isolation, quarantine, and social distancing must be followed. Infected persons should take precautions while sneezing or coughing.
Sanitization of environment, dietary modifications and health-promoting herbs should be used as mentioned above 50.
(b) Proposed Management: Al Asbab wa-Alamat prescribes the care of nazla-e-wabaiya through immunomodulatory, anti-inﬂammatory, and antipyretic drugs like the decoction of Unnab (Ziziphus jujube Mill., Rhamnaceae) 5 no., Behidana (Cydonia oblonga Mill., Rosaceae) 3g,Sapistan (Cordia dichotoma G. Forst., Boraginaceae) 9 no., and Khaksi (Sisymbrium adenophorum Tidestr., Brassicaceae) 5g. If the patients suffer from associated diarrhea, habb-ul aas (Myrtus communis L., Myrtaceae) and tabasheer (Bambusa bambos (L.) Voss, Poaceae) are also given. To allay thirst, Sheera tukhm e kahu (Lactuca sativa L., Compositae, seed paste) may be advised.
In case of pneumonia or pleurisy, Aloe vera L. sap (1 g), qairooti aarad karsana (10 g), C. sativus L. stamen (1g) are compressed, mixed, warmed moderately and applied on the chest and shielded with a cotton bandage 63, 64. A polyherbal Unani formulation - Qairooti aarad karsana consisting of Aarad e Karsana (Pisum sativum L., Leguminosae, ﬂour), Aarad e Hulba (Trigonella adscendens (Nevski) Afan. & Gontsch., Leguminosae, ﬂour) - 60g each, Kalonji (Nigella sativa L., Ranunculaceae, seeds), Asl-us-Soos (Glycyrrhiza glabra L., Leguminosae, root) – 24 g each, Aqarqarha (Anacyclus pyrethrum (L.) Lag., Compositae, root) - 18g, Roghan-e-Sosan (Iris ensata Tunb., Iridaceae, oil) and Bees Wax- both in equal amount, quantum satis, to make a paste is given for chest diseases 65.
3.3 Homeopathy System of Medicine: Previously, the uses of homeopathic intervention as preventive measure in various viral infections are evident 66. Understanding the pathophysiology and studies of various clinical cases helps to establish a correlation of symptoms with the extent of infection. The collected information can be utilized to discover specific homeopathic treatment regimen suitable for patient’s condition 67, 68. Based on the evidences of prophylactic and curative homeopathic medicine’s efficacy against previous viral epidemics like Spanish influenza, yellow fever, scarlet fever etc., proven 66, 68. Specific observations and studies on symptoms and particular patient conditions in various cases produce sufficient information on the homeopathic system’s efficacy against several epidemic diseases 69, 70. Clinical trials associated with specific viral infections and the efficacy of homeopathic medicines revealed a successful benefit in the health and recovery process 71, 72. Considering all previous studies facts and outcomes, homeopathic medicine system is suggested as adjuvant approaches along with critical care of COVID-19. Homeopathic medicine Arsenicum Album-30 is a preventive care drug for flu-like symptoms of COVID-19. Scientific publications from the Ministry of AYUSH and other government issue notes and guidelines on the utility of homeopathic medicine-induced preventive actions against infective disease by boosting immunity and reducing pathophysiological interventions 73-76.
3.4 Traditional Chinese Medicine: The involvement of traditional Chinese Medicine can help to decrease the severe symptoms of patients suffering from infectious diseases. The strategy for the management of viral infection involves the following:
(1) Prevention: According to TCM, Qi is the fundamental substance constituting the human body responsible for maintaining the primary functions. Thus, there are two types of Qi. Healthy Qi mentions the substances which maintain the normal functions of the body. Pathogenic Qi includes unhealthy matter.
As the lungs are very delicate, firstly, their function gets affected. The clinical evidence of COVID-19 patients classify ‘wet’, ‘heat’, and ‘congestion’ in their lungs. ‘Wet’ refers to component with sticky and heavy turbidity resulting into long duration of disease and damaging the lung function. ‘Heat’ cites the element with hot, dry, and rising turbidity that can produce the disease. ‘Congestion’ is an actuating component that can obstruct blood circulation and can result into manifestations such as pain.
Thus, the preventive strategy of TCM targets to protect the lungs. Yupingfeng San 77, is a traditional Chinese herbal formula used to protect lung Qi and avoid pathogenic Qi. This formulation comprises of 20 g Astragalus, 15 g Fanfeng and 15 g Astractylodes. These three herbs are mixed and boiled together in 1000 ml pure water. These are boiled to obtain 600 ml of the tincture. It is then given in the dosage of 200 ml orally once, three times a day. Earlier studies have exhibited that this formulation could manage the immune function of the body. Astragalus can upgrade lung Qi and can decrease phlegm. Fangfeng can alleviate the pathogenic Qi, remove dampness and allay pain. Atractylodes strengthen the spleen Qi, which can influence digestion and absorption 8.
(2) Treatment of Mild Infection: Fever, sweat, headache, cough, sore throat, thirst, red tongue tip, thin white or pale-yellow coating, and floating pulse are symptoms of mild infection. As per TCM theories, the pathogenic Qi, damages the lung Qi. The disruption in lung Qi results in lung heat and dampness, causing the typical symptoms of fever, sore throat, cough, and fatigue. So, such herbal formulations are used in mild infections, which can ‘clear the lung heat and dampness’ to heal it. Sangju yin and Yinqiao san are prescribed for clearing the lung heat, removing phlegm, soothing cough, regulating the lungs, and restoring normal lung function. Clinically Sangju yin is prescribed for patients with severe cough and Yinqiao san for patients with a high fever.
The formula of Sangjuyin consists of Mulberryleaf 15 g, Mint 6g, Chrysanthemum 10 g, Forsythia 10 g, Chinese bellflower6g, Reed root 15 g, Almond 9 g, and Licorice 3 g. Yinqiao contains san Forsythia 15 g, Burdock 6 g, Bamboo leaves 6 g, Chinese bellflower6g, Mint 6 g, Honeysuckle 15 g, Licorice 3 g, Nepeta 6 g, and Lighttempeh 5 g. The medicinal herbs are mixed and boiled together in 1000 ml pure water. These are boiled to obtain 600 ml of the tincture. They are then given in the dosage of 200 ml orally once, three times a day 8.
Few research investigations have also revealed that Yinqiao san may have antibacterial and antiviral activity. It may also improve the immune function of the upper respiratory tract 78.
Treatment of Severe Symptoms: The National Health Commission and the National Administration of Traditional Chinese Medicine of the People’s Republic of China developed clinical guidelines for the management of COVID-1979.If the infection could not be managed in mild condition, then the manifestations of infectious patients involve high fever, cough, phlegm, difficult breathing, sweating, chest tightness, fatigue, nausea, bloating, red or dark red tongue, yellow coating, slippery or weak pulse, failure of the respiratory system and other vital organs resulting into death. As stated by TCM, if primary care is ineffective, or the pathogenic Qi is too powerful, the healthy Qi will be impaired seriously, and lungs will stop functioning. The sputum will be produced increasingly, and the patient will be unable to breathe. Maxingshigantang (decoction) and Baihegujin tang can be used to comfort the healthy Qi, remove the pathogenic Qi and assist the lung to get rid of sputum and receive air 8.
Maxingshigan tang comprises Ephedra 15 g, Almond 10 g, Licorice 9 g, and Plaster 20 g. The formula for Baihegujin tang contains Shudihuang 15 g, Xuanshen 10 g, Dihuang 15 g, Angelica 15 g, White peony 6 g, Chinese bellflower 6g, Beimu 6 g, Licorice 3 g, Ophiopogon 6 g, Lily 6 g. These medicinal herbs are mixed and boiled together in 1000 ml pure water. These are boiled to obtain 600 ml of the tincture. They are then given in the dosage of 200 ml orally once, three times a day. Maxinshigan tang is basically used to clear lung fever and decrease phlegm. Baihegujin tang can revitalize the lung Qi. These two formulations are mixed together in case of severe infection, which results into healthy Qi and removal of the pathogenic Qi 8.
Recent Evidence of uses of Herbs for Covid-19: Currently, many research investigations are being carried out for finding the most potent drug candidate for COVID-19.
A review by Boone and Custonic, has stated the utility of herbs to combat COVID-19. Vitamin C (from oranges, kiwi, kale, and broccoli), Magnesium (from black beans, avocado, and whole grains), Moringa, Reishi, and Curcumin can be taken to augment our immune system. The natural drugs which can be beneficial for our respiratory system are licorice, sage, thyme, garlic, ginger, cinnamon, honey, orange, and marshmallow roots. Eucalyptus and sage infusion can be used in the form of inhalation for respiratory troubles. Eucalyptus, mullein, sage, garlic, licorice, and thyme have been reported to alleviate the symptoms of cough, shortness of breath, and pneumonia. Feverfew, yarrow, chamomile, holy basil, turmeric, nettle, and clove given in the form of tea/infusion/capsules exhibit anti-inflammatory properties. The study has also stated that most of the herbal drugs can be taken in the form of an infusion, decoction, extract, tincture, pills, capsules, pastilles, syrup, or honey infusion. Velvet tea (decoction of marshmallow root and licorice) is also highly beneficial 80.
Patanjali has proposed a treatment regime for the treatment of COVID-19. This includes few herbal medicines in combination with ICMR approved hydroxychloroquine. All these drugs were investigated for their potential against COVID-19. To search for most suitable herbal drug, more than 1000 phytoconstituents were screened in silico. They were studied for their binding affinities to COVID-19 essential proteins and host protein interactions. The study revealed that withanone from Ashwagandha, tinocordiside from Giloy, and scutellarein from Tusli docked very well in the bonding interface of ACE2-RBD complex 81.
FDA-approved antiviral phytochemicals were screened using PyRx virtual screening tool targeting the proteases of SARS-CoV-2. The study revealed that Rhein (-8.1) WithanolideD(-8), WithaferinA (-7.7), Enoxacin (-7.4), and Aloe-emodin (-7.4)exhibited ADME characteristics. Thus, these Phytoconstituents may be utilized as probable inhibitors against SARS-CoV2 Main Protease after their proper validation 14.
In another in-silico study, the potential of few herbal compounds was compared against COVID-19. Molecular docking analysis was done through AutoDock Vina, and the most suitable ligand was recognized on the basis of their binding energy. The research concluded by stating that ‘Quercetin, Hispidulin, Cirsimaritin, Sulfasalazine, Artemisin, and Curcumin exhibited better potential inhibition than Hydroxy-Chloroquine against COVID-19 main protease active site and ACE 82.
Research screened the potency of phytochemicals from Curcuma sp., Citrus sp., Alpinia galanga, and Caesalpinia sappan against SARS-CoV-2 through molecular docking using the MOE 2010 program. The study concluded indicating that flavonoids from Citrus sp. followed by galangin from galangal, brazilin from sappan wood, and curcumin from Curcuma sp exhibited potential as SARS-CoV2 inhibitor. Thus, these drugs can be consumed in daily life for prophylaxis of COVID-19 83.
Another recent study against the viral receptors using the molecular docking technique identified 6-gingerol as an excellent phytochemical possessing remarkable pharmacokinetic properties with the highest binding affinity ranging from -2.8764 KJ/mol to -15.7591 KJ/mol with various COVID-19 viral protein targets. Thus, 6-gingerol from ginger could be used a potent medicine for COVID-19 84.
Hesperidin, naringin, and pectin from citrus peels have also proved their potency against COVID-19 through a recent computational and experimental study 85.
Further, the compounds from Nigella sativa underwent docking studies through Molecular Operating Environment Software (MOE). The results were stated as “Nigelledine docked into 6LU7 active site gives energy complex about -6.29734373 Kcal/mol which is close to the energy score given by chloroquine (-6.2930522 Kcal/mol) and better than energy score given by hydroxychloroquine (-5.57386112 Kcal/mol) and favipiravir (-4.23310471 kcal/mol).
Docking into 2GTB active site showed that a- Hederin gives an energy score of about-6.50204802 kcal/mol, which is a better energy score given by chloroquine (-6.20844936 kcal/mol), hydroxyl-chloroquine (-5.51465893 kcal/mol)) and favipiravir (-4.12183571 kcal/mol).” Nigellidine and α-Hederin from Nigella sativa emerged to be the most suitable drug candidate against COVID-1986. A study expressed that the use of drugs such as Zingiber officinale, Scutellaria baicalensis, Nigella sativa, Hypericum perforatum, Glycyrrhiza glabra, Echinacea spp., Camellia sinensis, and Allium sativum, can help in improving the immune response. The phytoconstituents from these plants have shown inhibitory effects against the various targets of corona virus-like S protein. They can also restrain the replication of many viral enzymes like helicase, Plpro, 3CLpro, etc. 87
Additionally, the in silico evaluation of the constituents of essential oils of Eucalyptus and Corymbia species such as eucalyptol, 3-carene, alpha-terpineol, citronellol, d-limonene, o-cymene, and alpha-pinene showed that these phyto-molecules can be utilized as a potent inhibitor of coronavirus 88.
A recent study concluded that glyaspein, isorhamnetin, acetoside, and numerous flavonoids might be beneficial in the management of COVID-19 by a reduction in the cytokine storm of the host, controlling the immune reaction and safeguarding the organs 89.
One of the strategies for the management of infection due to coronavirus state that the drugs and herbs should be given along with the balanced diet, nutraceuticals, nutritional supplements, vitamins and micronutrients. This would help in decreasing hospitalization and complications of the respiratory system 90.
Likewise, two different computational studies on phytoconstituents from official Siddha formulations: Nilavembu kudineer (Mentioned in the Siddha text Siddha Vaithiya Thirattu effective against Dengue and Chikunguniya virus) 91 and Kabasura Kudineer (used in treating viral fever and respiratory diseases) 92 have also been carried out. The results revealed that Benzene 123 Triol from Nilavembu Kudineer Chooranam could bind against the ACE2 receptor with a low glide score of -6.185 Kcal/mol. The in-silico analysis of Kabasura Kudineer showed that nine compounds possessed high binding affinity 92.
Ma Xing Shi Gan Decoction (MXSGD) – a combination of modern medicine and TCM was investigated for its mechanism for the treatment of COVID-19. Around 97 active components were screened, and 169 targets were projected. Some of these included Heat shock protein-90, RAC-alpha serine/threonine-protein kinase, Transcription factor AP1, Mitogen-activated protein kinase1, Cellular tumor antigen p53, Vascular endothelial growth factor A and Tumor necrosis factor. The study concluded by stating, “The therapeutic mechanisms of MXSGD on COVID-19 may primarily involve the following effects: reducing inflammation, suppressing cytokine storm, protecting the pulmonary alveolar-capillary barrier, alleviating pulmonary oedema, regulating the immune response, and decreasing fever” 93.
Respiratory Detox Shot, a lung toxin dispelling formula based on TCM was investigated in a study for its mechanism of action. TCM databases revealed the presence of 1071 known phyto-chemicals from the nine ingredients. Of these 157 qualified the drug-likeness screening and exhibited 339 anticipated targets in the constituent network. The molecular docking utilizing computational pattern recognition revealed that 118 phyto-molecules showed a high binding affinity with SARS-coronavirus-2, 3-chymotrypsin-like protease (3CL pro). The 3CL inhibition assay was used to validate the in vitro activity of 22 phytoconstituents of RDS. The study concluded that RDS may be used in general treatment for early stages of COVID-19 94.
An Ayurvedic Text has mentioned the use of herbal preparation containing Zingiber officinale and Citru medica for nasal rinse to manage the contagious fevers. Keeping this fact in mind, a in silico study was conducted to explore the potential of the components of these herbs in management of COVID-19. The findings revealed that the Phyto molecules in these plants had an attraction for virus spike protein and host’s ACE-2 receptor. This would finally lead to the decrement of viral load and detaching of SARS-CoV-2 from the nasal passages 95.
Balkrishna et al., have reported that a herbal preparation consisting of extracts of Tinospora cordifolia, Withania somnifera, and Ocimum sanctum might be beneficial against SARS-CoV-2. The computational studies have revealed that the phytochemicals of herbs present in coronil could inhibit the entry of SARS CoV-2 into the host cell and related cytokines’ production. It could hamper the interface of ACE-2 with SWT (wild-type S protein) and also with SD614G (more infectious variant). The elevated level of IL-6, IL-1β, and TNF-α in A549 cells also reduced after treatment with Coronil 96. In another research investigation, Balkrishna et al., performed the analytical evaluation of Divya-Swasari-Vati, which is a herbal medication containing calcium prepared for providing relief from the respiratory symptoms due to corona infection. The study identified and quantified eleven active marker phytocompounds gallic acid, methyl gallate, coumarin, proto-catechuic acid, ellagic acid, cinnamic acid, proto-catechuic acid, glycyrrhizin, glabridin, eugenol, piperine and 6-gingerol 97. Additionally, Balkrishna et al., conducted a survey to study the satisfaction of patients for Divya-Swasari-Coronil-Kit Against COVID-19. The study concluded that this kit possesses a positive and valuable inference on psychosomatic wellbeing and Quality of life 98.
Although, an array of herbal drugs has been suggested to be safe and efficacious for the management of COVID-19, but a research investigation targeted to unveil the associated toxic effects of some of these herbs such as Oleandrin, Datura, Ephedra, and Glycyrrhizin. According to Phoenix Biotechnology, Oleandrin could help in the treatment of COVID-19. But later FDA denied its approval as a dietary supplement due to its associated poisoning manifested by nausea, vomiting, and abdominal pain followed by debility, drowsiness, hyperkalemia, and cardiotoxicity. Datura seeds were also recommended for treatment of COVID-19, but in high doses, it exhibits indications such as hallucinations, thirst, blurred vision, and difficulty in speaking or swallowing followed by tachycardia, hyperthermia, seizures, and respiratory arrest 99.
CONCLUSION: Understanding the pathogenesis of CoV-2 and comparable information with previous viral infections propose opportunities to explore more treatment options. Phytochemical and herbal-based medicines are used and studied for their multi-mechanistic approaches against Co-V-2. Traditional medicinal systems provide immense knowledge and evidence for the efficacy of herbal-based preparations and phytoconstituents against various viral infections. Several researchers have evaluated different extracts, herbal-formulations and identified phytoconstituents against different mechanisms of viral attachment, endocytosis, unpacking, transcription, translation, viral replication, assembly formation, etc. and underlying and associated proteins and enzymes of CoV-2. Promising efficacy was evident on the basis of in-silico, and in-vitro studies proposed further investigations of these compounds and formulations. Hence, thorough investigation and evidence discussed above recommend further evaluation and investigation of herbal-based medicines for their safe and effective use against CoV-2.
DECLARATION OF COMPETING INTEREST: The authors declare that they have no competing interests.
ACKNOWLEDGEMENT: The authors would like to acknowledge the technical support from the KIET Group of Institutions, Delhi-NCR, Ghaziabad, for literature search.
AUTHOR CONTRIBUTIONS: Deepti Katiyar and Priya Bansal contributed for a review of traditional medicines and their correlation with previously reported antiviral efficacy. Abhishek Kumar and Manish reviewed the pharmacological and molecular targeting aspects of herbal compounds and formulations. Abhishek Kumar and Deepti Katiyar worked on the concept and design of the review.
FUNDING SUPPORT: The work is not supported by any funding.
- Ang L, Lee HW, Choi JY, Zhang J and Lee MS: Herbal medicine and pattern identification for treating COVID-19: a rapid review of guidelines.Integr. Integrative Medicine Research 2020; 100407.
- Biswas S, Chatterjee S, Dey T, Dey S, Manna S, Nandy A and Basak S: In-silico approach for peptide vaccine design for CoVID 19. 2020; 6: 1-10.
- Dhama K, Sharun K, Tiwari R, Dadar M, Malik YS, Singh KP and Chaicumpa W: COVID-19, an emerging coronavirus infection: advances and prospects in designing and developing vaccines, immunotherapeutics, and therapeutics. Human Vaccines & Immunotherapeutics 2020; 1-7.
- Cava C, Bertoli G and Castiglioni I: In-silico discovery of candidate drugs against covid-19. Viruses 2020; 12(4): 404.
- Jiang S, HillyerC and Du L: Neutralizing antibodies against SARS-CoV-2 and other human coronaviruses. Trends In Immunology 2020; 41(5): 355-59.
- Rane JS, Chatterjee A, Kumar A and Ray S: Targeting SARS-CoV-2 spike protein of COVID-19 with naturally occurring phytochemicals: an in-silco study for drug development. Chem Rxiv 2020. [cited 2020 Nov 29]; Available from: https://doi.org/10.26434/chemrxiv.1209v1.
- Dyall J, Coleman CM, Hart BJ, Venkataraman T, Holbrook MR, Kindrachuk J, Johnson RF, Olinger GG, Jahrling PB and Laidlaw M: Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection. Antimicrobial Agents and Chemotherapy 2014; 58(8): 4885-93.
- Xu J and Zhang: Traditional Chinese medicine treatment of COVID-19.Complementary Therapies in Clinical Practice 2020; 39: 101165.
- Vardhan S and Sahoo SK: Searching inhibitors for three important proteins of COVID-19 through molecular docking studies preprint. 2020; 2004: 08095.
- Ul Qamar MT, Alqahtani SM, Alamri MA and Chen L-L: Structural basis of SARS-CoV-2 3CLpro and anti-COVID-19 drug discovery from medicinal plants. Journal of Pharmaceutical Analysis 2020;10: 313-19.
- Cho JK, Curtis-Long MJ, Lee KH, Kim DW, Ryu HW, Yuk HJ and Park KH: Geranylated flavonoids displaying SARS-CoV papain-like protease inhibition from the fruits of Paulownia tomentosa. Bioorganic & Medicinal Chemistry 2013; 21(11): 3051-57.
- Elmezayen AD, Al-Obaidi A, Şahin AT and Yelekçi K: Drug repurposing for coronavirus (COVID-19): in-silico screening of known drugs against coronavirus 3CL hydrolase and protease enzymes. Journal of Biological Structure and Dynamics 2020; 1-12.
- Ryu YB, Jeong HJ, Kim JH, Kim YM, Park JY, Kim D, Naguyen TTH, Park SJ, Chang JS and Park KH: Biflavonoids from Torreya nucifera displaying SARS-CoV 3CLpro inhibition. Bioorganic & Medicinal Chemistry 2010; 18(22): 7940-47.
- Chandel V, Raj S, Rathi B and Kumar D: In-silico identification of potent COVID-19 main protease inhibitors from FDA approved antiviral compounds and active phytochemicals through molecular docking: A Drug Repurposing Approach. 2020; 2020030349. Available from: http://doi.org/10.20944/preprints202003.0349.v1.
- Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, Zhao X, Huang B, Shi W and Lu R: A novel coronavirus from patients with pneumonia in China 2019. New England Journal of Medicine 2020; 382: 727-33.
- Lung J, Lin YS, Yang YH, Chou YL, Shu LH, Cheng YC, Liu HT and Wu CY: The potential chemical structure of anti‐SARS‐CoV‐2 RNA‐dependent RNA polymerase. Journal of Medical Virology 2020; 92(6): 693-97.
- Gordon CJ, Tchesnokov EP, Feng JY, Porter DP and Götte M: The antiviral compound remdesivir potently inhibits RNA-dependent RNA polymerase from Middle East respiratory syndrome coronavirus. Journal of Biological Chemistry 2020; 295(15): 4773-79.
- Zhang L and Liu Y: Potential interventions for novel coronavirus in China: A systematic review. Journal of Medical Virology 2020; 92(5): 479-90.
- Cassidy L, Fernandez F, Johnson JB, Naiker M, Owoola AG and Broszczak DA: Oxidative stress in Alzheimer’s disease: a review on emergent natural polyphenolic therapeutics. Complementary Therapies in Medicine 2019; 49: 102294.
- Khan H, Sureda A, Belwal T, Çetinkaya S, Süntar İ, Tejada S, Devkota HP, Ullah H and Aschner M: Polyphenols in the treatment of autoimmune diseases. Autoimmunity Reviews 2019; 18(7): 647-57.
- Zhang DH, Wu KL, Zhang X, Deng SQ and Peng B: In silico screening of Chinese herbal medicines with the potential to directly inhibit 2019 novel coronavirus. Journal of Integrative Medicine2020; 18(2): 152-58.
- Keum YS and Jeong YJ: Development of chemical inhibitors of the SARS coronavirus: viral helicase as a potential target. Biochemical Pharmacology 2012; 84(10): 1351-58.
- Ganjhu RK, Mudgal PP, Maity H, Dowarha D, Devadiga S, Nag S and Arunkumar G: Herbal plants and plant preparations as remedial approach for viral diseases. Virusdisease 2015; 26(4): 225-36.
- Luo H, Tang QL, Shang YX, Liang SB and Yang M: Robinson N and Liu Jp: Can Chinese medicine be used for prevention of corona virus disease 2019 (COVID-19)? A review of historical classics, research evidence and current prevention programs. Chinese Journal of Integrative Medicine 2020; 1-8.
- Rastogi S: Viral epidemics and traditional health care systems: It’s time to act honestly, proactively and collectively. Annals of Ayurvedic Medicine 2020; 9: 1-5.
- Vellingiri B, Jayaramayya K, Iyer M, Narayanasamy A, Govindasamy V, Giridharan B, Ganesan S, Venugopal A, Venkatesan D and Ganesan H: COVID-19: A promising cure for the global panic. Science of the Total Environment 2020; 25: 138277.
- Gomathi M, Padmapriya S and Balachandar V: Drug studies on Rett syndrome: from bench to bedside. Journal of Autism and Developmental Disorders 2020; 1-25.
- Yu S, Wang J and Shen H: Network pharmacology-based analysis of the role of traditional Chinese herbal medicines in the treatment of COVID-19. Annals of Palliative Medicine 2020; 9(2): 437-46.
- Zhang D, Zhang X, Peng B, Deng S, Wang Y, Yang L, Zhang K, Lin C and Wu K: Molecular Basis for Treating COVID-19 with Official Chinese Herbal Formula LCTE.2020 May. [cited 2020 November 23] Available from: http://doi.org/10.21203/rs.3.rs-20828/v1.
- Jyotirmoy S and Rekha SD: Concept of Epidemic Diseases in Ayurveda. International Journal of Health Research and Medico Legal Practice 2016; 2(01): 24.
- Patwardhan B, Chavan-Gautam P, Gautam M, Tillu G, Chopra A, Gairola S and Jadhav S: Ayurveda rasayana in prophylaxis of covid-19. Current Science 2020; 118: 1158-60.
- Rastogi S, Pandey DN and Singh RH: COVID-19 Pandemic: A pragmatic plan for Ayurveda Intervention. Journal of Ayurveda and Integrative Medicine2020 April. [cited 2020 November 24]. Available from: http://doi.org/10.1016/j.jaim.2020.04.002
- AYUSH T: Ayurveda’s immunity boosting measures for self care during COVID 19 crisis. YaN The Ministry of Ayurvedic, Unani, Siddha and Homeopathy (AYUSH), editor. 2020.
- Hotchkiss RS and Opal SM: Activating immunity to fight a foe—a new path. New England Journal of Medicine 2020; 382(13): 1270-72.
- Rani P, Sharma K and Kumar A: Probable mode of action of Sanjivani vati-a critical review. International Journal of Health Sciences and Research 2018; 8: 295-07.
- Tripathi J and Singh R: Possible correlates of free radicals and free radical mediated disorders in ayurveda with special referance to bhutagni vyapara and ama at molecular Level. Ancient Science of Life 1999; 19(1-2): 17.
- Panche AN, Chandra S and Diwan AD:Multi-target β-protease inhibitors from Andrographis paniculata: in-silico and in-vitro Plants 2019; 8(7): 231.
- Rege A and Chowdhary AS: Evaluation of Ocimum sanctum and Tinospora cordifolia as probable HIV protease inhibitors. International Journal of Pharmaceutical Sciences Review and Research 2014; 25(1): 315-18.
- Rege A and Chowdhary A: Evaluation of some medicinal plants as putative HIV-protease inhibitors. Indian Drugs 2015; 50: 24-28.
- Singh A: Regulatory and Pharmacological Basis of Ayurvedic Formulations.CRC Press. Florida, United States 2017.
- Bisht D, Sharma Y and Mehra B: A clinical study to evaluate the efficacy of Pippali Rasayana in certain respiratory disorders. AYU (An international quarterly journal of research in Ayurveda) 2009; 30(3): 337.
- Makhija IK, Shreedhara CS and Ram HA: Mast cell stabilization potential of Sitopaladi churna: An ayurvedic formulation. Pharmacognosy Research 2013; 5(4): 306.
- Rastogi S and Srivastav P: Ayurveda in critical care: Illustrating Ayurvedic intervention in a case of hepatic encephalopathy. Ayush 2011; 32(3): 345.
- Panigrahi HK: Efficacy of Ayurvedic medicine in the treatment of uncomplicated chronic sinusitis. Ancient Science of Life 2006; 26(1-2): 6.
- Sharma R and Prajapati P: Nanotechnology in medicine: Leads from Ayurveda. J Journal of Pharmacy and Bioallied Sciences 2016; 8(1): 80-81.
- Math SB, Moirangthem S and Kumar CN: Public health perspectives in cross-system practice: past, present and future. Indian J of Medical Ethics 2015; 12(3): 131-36.
- Sina I and Al Qanoon Fil Tib: Mataba Munshi Naval Kishore, Lucknow, India 2007; 522..
- Razi Z and Kitab Al-Mansoori: Central Council for Research in Unani Medicine. Ministry of Health and Family Welfare, New Delhi, Govt. of India 1991; 1: 326-28.
- Parvez A, Ahmed Z, Anwar N and Ahmed K: Razi’s unique approach to Amraz-e-Wabaiya (Infectious Diseases): An overview. International Journal of Herbal Medicine 2016; 4(6): 176-78.
- Nikhat S and Fazil M: Overview of Covid-19; its prevention and management in the light of Unani medicine. Science of the Total Environment 2020 April. [cited 2020 December 1]; 728, 138859. Available from: http://doi.org/10.1016/j.scitotenv.2020.138859.
- Kim J, Jang M, Shin E, Kim J, Lee SH and Park CG: Fumigant and contact toxicity of 22 wooden essential oils and their major components against Drosophila suzukii (Diptera: Drosophilidae). Pesticide Biochemistry and Physiology 2016 ;133: 35-43.
- Alam MA, Haider N, Ahmed S, Alam MT, Azeez A and Perveen A: Tahlab (Spirulina) and few other medicinal plants having anti-oxidant & immunomodulatory properties described in Unani medicine-A review. International Journal of Pharmacy and Pharmaceutical Sciences 2013; 4(11): 4158.
- Ho CW, Lazim AM, Fazry S, Zaki UKHH and Lim SJ: Varieties, production, composition and health benefits of vinegars: A review. Food Chemistry 2017; 221: 1621-30.
- Imani G, Dastan D, Imani B and Mehrpooya M: Effects of cinnamon extract on complications of treatment and eradication of Helicobacter pylori in infected people. Journal of Herbmed Pharmacology 2019; 9(1): 55-60.
- Bassiri-Jahromi S: Punica granatum (Pomegranate) activity in health promotion and cancer prevention. Oncology Reviews 2018; 12(1).
- Pandith SA, Dar RA, Lattoo SK, Shah MA and Reshi ZA: Rheum australe, an endangered high-value medicinal herb of North Western Himalayas: a review of its botany, ethnomedical uses, phytochemistry and pharmacology. Phytochemistry Reviews 2018; 17(3): 573-09.
- Parsley NC, Kirkpatrick CL, Crittenden CM, Rad JG, Hoskin DW, Brodbelt JS and Hicks LM: PepSAVI-MS reveals anticancer and antifungal cycloviolacins in Viola odorata. Phytochemistry 2018; 152: 61-70.
- Rahmani AH: Cassia fistula Linn: Potential candidate in the health management. Pharmacognosy Research 2015; 7(3): 217.
- Zeinali M, Zirak MR, Rezaee SA, Karimi G and Hosseinzadeh H: Immunoregulatory and anti-inflammatory properties of Crocus sativus (Saffron) and its main active constituents: A review. Iranian Journal of Basic Medical Sciences 2019; 22(4): 334.
- Lim SH and Choi C-I: Pharmacological properties of Morus nigra(black mulberry) as a promising nutraceutical resource. Nutrients 2019; 11(2): 437.
- Komakech R, Kim Yg, Matsabisa GM and Kang Y: Anti-inflammatory and analgesic potential of Tamarindus indica (Fabaceae): a narrative review. Integrative Medicine Research 2019; 8(3): 181.
- Sharafati FS, Saholi M and Sharafati RS: Chemical composition, antioxidant and antibacterial activity of Bunium persicum, Eucalyptus globulus, and Rose Water on multidrug-resistant Listeria species. Journal of Evidence-Based Integrative Medicine 2018; 23: 1-7.
- Bughdadi I: Kitab al Mukhtarat Fil Tib. Part I, New Delhi: Central Council of Research in Unani Medicine 2005.
- Kirmani N: Sharah Al asbab wal Alaamat (Urdu translation). Aijaz Publication House, New Delhi 2007; 6: 164-70.
- India Ministry of H Family W India, Department of Indian Systems of M Homoeopathy, India, Department of Ayurveda, Y Naturopathy, U.S., Homoeopathy, 1983. National formulary of Unani medicine. Govt. of India, Ministry of Health and Family Welfare, Dept. of Health, New Delhi.http://www.worldcat.org/oclc/12161296 (accessed 1 June, 2020).
- Jacobs J: Homeopathic prevention and management of epidemic diseases. Homeopathy 2018; 107(03): 157-60.
- Hahnemann S: The lesser writings of Samuel Hahnemann. B. Jain Publishers, Noida, India 2002.
- Thomas M, Suresh A and Thiagaraj AP: Development of homoeopathic genus epidemicus for secondary level prevention of dengue virus infection at Kannur, Kerala. 2018 April. [cited november 10]: Available from: https://www.researchgate.net/publication/326464077.
- Dewey W: Homeopathy in influenza: a chorus of fifty in harmony. J Am Inst Homeopath 1921; 11: 1038-43.
- Teixeira MZ: Homeopathy: a preventive approach to medicine? International Journal of High Dilution Research 2009; 29: 155-72.
- Golden I: Large scale homœoprophylaxis: results of brief and long-term interventions. American Journal of Homeopathic Medicine. 2019 May. [cited 2020 December 2]. Available from: https://www.ccrhindia.nic.in/showimg. aspx?ID=15677.
- Nayak D, Chadha V, Jain S, Nim P, Sachdeva J, Sachdeva G, Vivekanand K, Khurana A, Raheja SM and Manchanda RK: Effect of adjuvant homeopathy with usual care in management of thrombocytopenia due to dengue: a comparative cohort study. Homeopathy 2019; 108(03): 150-57.
- Bellavite P, Signorini A, Marzotto M, Moratti E, Bonafini C and Olioso D: Cell sensitivity, non-linearity and inverse effects. Homeopathy 2015; 104(02): 139-60.
- Chakraborty P, Lamba C, Nayak D, John M, Sarkar D, Poddar A, Arya J, Raju K and Prusty A: Effect of individualized homoeopathic treatment in influenza like illness: A multicenter, single blind, randomized, placebo controlled study. Indian Journal of Research in homoeopathy 2013; 7(1): 22-30.
- Gupta J, Rao MP, Raju K, Prasad R, Arya J, Mondal B, Sadanandan G, Singh M, Singh V and Nayak C: Management of early years of simple and mucopurulent chronic bronchitis with pre-defined homeopathic medicines-a Prospective Observational Study with 2-Years Follow-Up. International Journal of High Dilution Research 2019; 18: 3-4.
- Mathie RT, Baitson ES, Frye J, Nayak C, Manchanda RK and Fisher P: Homeopathic treatment of patients with influenza-like illness during the 2009 A/H1N1 influenza pandemic in India. Homeopathy 2003; 102(03): 187-92.
- Lau JT, Leung P, Wong E, Fong C, Cheng K, Zhang S, Lam C, Wong V, Choy K and Ko W: The use of an herbal formula by hospital care workers during the severe acute respiratory syndrome epidemic in Hong Kong to prevent severe acute respiratory syndrome transmission, relieve influenza-related symptoms, and improve quality of life: a prospective cohort studyournal of Alternative and Complementary Medicine 2005; 11(1): 49-55.
- Liu L-S, Lei N, Lin Q, Wang W-L, Yan H-W and Duan X-H: The Effects and Mechanism of Yinqiao Powder on Upper Respiratory Tract Infection. Int J Biotechnol Wellness Ind 2015; 4(2): 57-60.
- Deng SQ and Peng HJ: Characteristics of and public health responses to the coronavirus disease 2019 outbreak in China.Journal of Clinical Medicine 2020; 9(2): 575.
- Boone HA, Čustović A, Hotić S, Latinović D and Sijerčić A: How to Fight COVID-19 Using a Healthy Lifestyle Approach. 2020 July. [cited 2020 November 23]: Available from: https://doi.org/10.13140/RG.2.2.24337. 58725.
- Balkrishna A: Indian traditional ayurvedic treatment regime for novel coronavirus, COVID-19. 2020.
- Sekiou O, Ismail, B, Zihad B and Abdelhak D: In-silico identification of potent inhibitors of COVID-19 main protease (Mpro) and angiotensin converting enzyme 2 (ACE2) from natural products: Quercetin, Hispidulin, and Cirsimaritin exhibited better potential inhibition than hydroxy-chloroquine against COVID-19 main protease active site and ACE2. ChemRxiv. Preprint. 2020. https://doi.org/10.26434/chemrxiv.12181404.v1.
- Utomo RY and Meiyanto E: Revealing the potency of citrus and galangal constituents to halt SARS-CoV-2 infection. Preprints 2020, 2020030214 (doi: 10.20944/ preprints202003.0214.v1).
- Rathinavel T, Palanisamy M, Palanisamy S, Subramanian A and Thangaswamy S: Phytochemical 6-Gingerol–A promising Drug of choice for COVID-19. International Journal of Advanced Research in Science, Engineering and Technology 2020; 6(4): 1482-89.
- Meneguzzo F, Ciriminna R, Zabini F and Pagliaro M: Hydrodynamic cavitation-based rapid expansion of hesperidin-rich products from waste citrus peel as a potential tool against COVID-19. Processes 2020; 8: 549.
- Bouchentouf S and Missoum N: Identification of compounds from Nigella sativa as new potential inhibitors of 2019 novel coronasvirus (Covid-19): Molecular Docking Study. Chem Rxiv. Preprint. 2020.https://doi.org/ 10.26434/chemrxiv.12055716.v1
- Boozari M and Hosseinzadeh H: Natural products for COVID-19 prevention and treatment regarding to previous coronavirus infections and novel studies. Phytotherapy Research 2020; 1–13.
- Panikara S, Shobaa G, Arunc M, Sahayarayand JJ, Nanthinia AUR, Chinnathambie A, Alharbie SA, Nasiff O and Kimg HJ: Essential oils as an effective alternative for the treatment ofCOVID-19: Molecular interaction analysis of protease (Mpro) with pharmacokinetics and toxicological properties. Journal of Infection and Public Health 142021; 601–610. https://doi.org/10.1016/j.jiph. 2020.12.037
- Sha Li, Chien-Shan Cheng, Cheng Zhang, Guo-Yi Tang, Hor-Yue Tan, Hai-Yong Chen, Ning Wang, Agnes Yuen-Kwan Lai and Yibin Feng: Edible and herbal plants for the prevention and management ofCOVID-19. Frontiers in Pharmacology 2021; 12.
- Gasmi A, Chirumbolo S, Peana M, Noor S, Menzel A, Dadar M and Bjørklund G: The role of diet and supplementation of natural products in COVID-19 Prevention. Biological Trace Element Research: 1-4 .https://doi.org/10.1007/s12011-021-02623-3
- Walter TM, Justinraj CS and Nandini V: Effect of Nilavembu kudineer in the Prevention and Management of COVID–19 by inhibiting ACE2 Receptor. Siddha Papers 2020; 15: 1-8.
- Gangarapu K, KM K and MS S: In-silico computational screening of kabasura kudineer-official siddha formulation and JACOM-Novel Herbal Coded Formulation Against SARS-CoV-2 Spike protein 2020. https://doi.org/10.1016/jaim.2020.05.009
- Wang Y, Ma J, Wang S, Zeng Y, Zhou C, Ru Y,Zhang L, Lu Z, Wu M and Li H: Utilizing integrating network pharmacological approaches to investigate the potential mechanism of Ma Xing Shi Gan Decoction in treating COVID-19. European Review for Medical and Pharmacological Sciences 2020; 24(6): 3360-84.
- Zhang ZJ, WU WY, Hou JJ, Zhang LL, Li FF, Gao L, Wu XD, Shi JY, Zhang R and Long HL: Active constituents and mechanisms of Respiratory Detox Shot, a traditional Chinese medicine prescription, for COVID-19 control and prevention: network-molecular docking-LC-MSE analysis. Journal of Integrative Medicine 2020; 18(3): 229-41.
- Haridas M, Sasidhar V, Nath P, Abhithaj J, Sabu A and Rammanohar P: Compounds of Citrus medica and Zingiber officinale for COVID-19 inhibition: in-silico evidence for cues from Ayurveda. Future Journal of Pharmaceutical Sciences 2021; 7(13): 1-9.
- Balkrishna A, Haldar S, Singh H, Roy P and Varshney A:Coronil, a Tri-Herbal Formulation, Attenuates Spike-Protein-Mediated SARS-CoV-2 Viral Entry into Human Alveolar Epithelial Cells and Pro- Inflammatory Cytokines Production by Inhibiting Spike Protein-ACE-2 Interaction. Journal of Inflammation Research 2021; 14: 869–88.
- Balkrishna A, Verma S, Sharma P, Tomer M, Srivastava J and Varshney A: comprehensive and rapid quality evaluation method for the ayurvedic medicine divya-swasari-vati using two analytical techniques: UPLC / QToF MS and HPLC–DAD Pharmaceuticals 2021; 14: 297.
- Balkrishna A, Raj P, Singh P and Varshney A: Influence of patient-reported treatment satisfaction on psychological health and quality of life among patients receiving divya-swasari-coronil-kit against COVID-19: Findings from a Cross-Sectional “SATISFACTION COVID” Survey Patient Preference and Adherence 2021; 15: 899-09.
- DiPietro MA and Mondie C: Toxicity of herbal medications suggested as treatment for COVID-19: A narrative review Journal of the American College of Emergency Physicians Open 2021; 2: e12411; 1-7.
How to cite this article:
Katiyar D, Bansal P, Manish and Kumar A: Strategies of traditional systems of medicine combating with the current pandemic situation of Covid-19. Int J Pharm Sci & Res 2021; 12(6): 2982-94. doi: 10.13040/IJPSR.0975-8232.12(6).2982-94.
All © 2013 are reserved by the International Journal of Pharmaceutical Sciences and Research. This Journal licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.
D. Katiyar, P. Bansal, Manish and A. Kumar *
Division of Pharmacology, KIET School of Pharmacy, KIET Group of Institutions, Delhi-NCR, Ghaziabad, Uttar Pradesh, India.
19 December 2020
11 May 2021
13 May 2021
01 June 2021