Novel Coronavirus (COVID-19) and Hopes around the Golden Spice “TURMERIC”: Fact sheet
Dr. H.N.Shivaprasad Ph.D.
Managing Director, Manipal Natural Pvt Ltd, INDIA
Write at : shiv@manipalnatural.com
The 2019 novel coronavirus (2019-nCoV, COVID-19) has spread in nearly 213 Countries, infected 1918138 patients, and resulted in 123,126 deaths worldwide (According to the current situational report from WHO, released on April 15, 2020).
Golden Spice Turmeric
Curcumin is the primary active compound in turmeric root, a traditional Indian medicine and cooking spice that has been valued for its healing properties for thousands of years in Ayurveda. Their medicinal and useful properties are mentioned in Indian Veda’s. Curcumin is the principal curcuminoid of the popular Indian spice turmeric. The other two curcuminoids are desmethoxycurcumin and bis-desmethoxycurcumin. The curcuminoids are polyphenols and are responsible for the yellow color of turmeric. Turmeric is one of the most extensively researched natural product of the modern age, with more than 3000 published research studies investigating its wide range of potential health benefits. A powerful antioxidant, curcumin is thought to support heart, brain, joint, and overall health by promoting healthy circulation and a healthy inflammatory response and by reducing oxidative stress. Accumulated evidence indicated curcumin plays an inhibitory role against infection of numerous viruses. These mechanisms involve either a direct interference of viral replication machinery or suppression of cellular signalling pathways essential for viral replication, such as PI3K/Akt, NF-κB.
Curcumin enhances immunity
“Immunity” is the body’s natural defence against disease-causing bacteria and virus. It is only due to the weak immunity that people are getting affected with the widespread coronavirus and other such pandemics. Many researchers have documented increased antibodies and immune boosting action when taken curcumin internally. Turmeric rhizome can be prepared in various ways and is reputed to alleviate asthma and coughs. Hot water extracts of the dried rhizome have been taken orally in Ayurvedic medicine to reduce inflammation. Turmeric is also regarded as a ‘rasayana’ herb, which is a branch of Ayurvedic medicine. Here turmeric is used to counteract ageing processes.
While announcing an extension to the nationwide lockdown till the 3rd May, 2020 to increase the social distancing amidst the coronavirus pandemic that is hitting the country and the world, the Indian Prime minister Shri Narendra Modi also recommended on a series of precautions that Indian citizens can take to boost their general immunity. The PM was seen recommending the AYUSH Ministry advisory on the matter. Ministry of AYUSH recommends the self-care guidelines for preventive health measures and boosting immunity with special reference to respiratory health. These are supported by Ayurvedic literature and scientific publications. AYUSH Ministry guidelines recommends to take Golden milk (made from Turmeric) once or twice daily.
Scientists focus around Turmeric to fight against COVID-19
According to scientist from University of Zulia, Venezuela and their publication posted 06.04.2020 as preprint in Research Square (DOI 10.21203/rs.3.rs-21206/v1); used strategies docking and molecular dynamics to analyze phytochemical compounds against FDA-approved antimalarial drugs recommended for the treatment of COVID-19. The evaluation was performed with the docking scores MolDock Score and Rerank Score calculated by Molegro Molecular. Preliminary results suggested that piperine, capsaicin, and curcumin have the best docking scores and that they are capable of promoting structural changes in the viral protease (3CL-protease) by inducing folding of the enzyme. Curcumin and capsaicin bring the enzyme to a more compact conformational state compared to the native state, compared to two anti-malarial drugs, chloroquine and Hydroxychloroquine. Scientist propose further studies and also mention the results are interesting because they can serve as a starting point for subsequent experimental.
Molecular docking study [Siti Khaerunnisa et al., Preprints, posted on 13.03.2020] revealed phytocompounds like kaempferol (sources: spinach, cabbage, dill), quercetin (sources: dill, fennel leaves, onion, chili pepper), luteolin-7-glucoside (sources: chili pepper, olive etc,) demethoxycurcumin (found in turmeric), naringenin (found in citrus fruits), apigenin-7-glucoside (found in celery leaves, olive etc,), curcumin (found in turmeric), catechin (source: amla, tea leaves, green tea), gingerol (from ginger), allicin (from garlic) and epicatechin-gallate (found in green tea) were the most recommended compounds found in medicinal plants that may act as potential inhibitors of COVID-19 Mpro (main protease).
In search of feasible interventions for the prevention and cure of novel coronavirus disease, a Principal Scientist from CSIR-Centre for Cellular and Molecular Biology made an attempt to identify (based on extensive literature search) some naturally occurring plant based substances and Ayurvedic medicinal herbs that could feasibly be tested as a matter of urgency for prevention as well as therapeutic option for COVID-19 in India and other parts of the world. He conclude in his publication as preprint posted on 24th March 2020 (doi: 10.20944/preprints202003.0353.v1) that dried rhizome of Curcuma longa L. i.e. turmeric, and its active ingredient curcumin may be effective in preventing as well as cure the COVID-19 pandemic due to its proven antiviral activities, this however need to be tested by appropriate clinical trials as research priority. Turmeric may act at an early step in SARS-CoV-2 infection by inhibiting its entry into the host cell as well as be effective in inhibiting the virus replication in human cells due to its anti-viral activities as demonstrated for HIV and AIDS, Zika and chikungunya and herpes simplex virus. It has also been shown that Zika and chikungunya virus incubated with curcumin loses its infectivity, this property of curcumin may also be explored for the possible inactivation of SARS-CoV-2 as a measure of urgency. Curcumin has been found to irreversibly inhibit Aminopeptidase N / CD13, indicating that curcumin could indeed be effective in preventing the Coronavirus infection by inhibiting its cell binding via CD13.
Scientist from Indian Institute of Technology, Mumbai; Indian Council of Medical Research (ICMR), Kolkota; Mahatma Gandhi Central University, Motihari, performed molecular docking study using 10 potential naturally occurring flavonoids/non-flavonoids against the SARS-CoV-2 spike protein and compared their affinity with the FDA approved drug hydroxychloroquine (HCQ) and published result in preprint posted on 09.04.2020 in ChemRxiV. Spike glycoprotein found on the surface of SARS-CoV-2 (SARS-CoV-2S) is a class I fusion protein which helps the virus in its initial attachment with human Angiotensin converting enzyme 2 (ACE2) receptor and its consecutive fusion with the host cells. The attachment is mediated by the S1 subunit of the protein via its receptor binding domain. Upon binding with the receptor the protein changes its conformation from a pre-fusion to a post-fusion form. The membrane fusion and internalization of the virus is brought about by the S2 domain of the spike protein. Interestingly, the docking analysis suggested that C-terminal of S1 domain and S2 domain of the spike protein are important for binding with these compounds. Kamferol, curcumin, pterostilbene, and HCQ interact with the C-terminal of S1 domain with binding energies of -7.4, -7.1, -6.7 and -5.6 Kcal/mol, respectively. Fisetin, quercetin, isorhamnetin, genistein, luteolin, resveratrol and apigenin on the other hand, interact with the S2 domain of spike protein with the binding energies of -8.5, -8.5, -8.3, -8.2, -8.2, -7.9, -7.7 Kcal/mol, respectively. Study suggested that, these flavonoid and non-flavonoid moieties have significantly high binding affinity for the two main important domains of the spike protein which is responsible for the attachment and internalization of the virus in the host cell and their binding affinities are much higher compared to that of HCQ.
Another group at Computational Biological Center, IBM Thomas J. Watson Research, New York, USA published in preprint posted on 31.03.2020 in ChemRxiV. They theoretically investigated the binding mechanism between the Mpro’s pocket (COVID-19, the main protease) and various marketed drug molecules being tested in clinics to fight COVID-19 that show promising outcomes. To inactivate the SARS-CoV-2 virus that causes COVID-19, the main protease (Mpro) that performs key biological functions in the virus has been the focus of extensive studies. They revealed an important ligand-binding mechanism for the Mpro that the binding stability of a ligand inside the Mpro pocket can be significantly improved if the partial ligand occupies the so-called “anchor” site of the Mpro. Along with the high-potent drugs/molecules (such as nelfinavir and curcumin) revealed in this study, the newly discovered binding mechanism paves the way for further optimizations and designs of Mpro’s inhibitors with a high binding affinity.
Curcumin has multifaceted function in curbing inflammation including, IL6, TNF- α, IL- 1β etc. and was also known to the protection over liver and gastrointestinal (GI) tract damage, which is common in COVID-19 pathological condition. Interestingly researchers found curcumin, forms the most stable (-7.1 kcal/mol) complex with SARS-CoV-2’s Mpro among the tested drugs. Researchers also mention a vital information on curcumin that there are some evidences that orally administered curcumin accumulates in sufficient quantity in the GI tract and liver. Besides the lung, the SARS-CoV-2 virus also infects the GI tract, causing the patients to experience also diarrhea. GI track and liver are immune privileged and may provide a shelter for SARS-CoV-2 virus from attacks by the immune system. Virus from the GI tract would be shedding off even after the lung tissue is free of viral infection, which could pose a great threat to infect others in shared bathrooms or via the aerosol formed in sewage system. Additionally, the GI system also expresses a high level of ACE2 receptors and TMPRSS2, which is critical for the SARS-CoV-2 infection. To prevent the GI system from providing a protective shelter for the SARS-CoV-2 virus, it is beneficial to take curcumin to curb the virus infection in the GI system during the drug treatment regime, and even after the viral infection being tampered in the lung.
Scientists from CSIR-CFTRI, (Council of Scientific and Industrial Research — Central Food Technological Research Institute) Mysore, India, based on in silico study (preprint posted on 10.04.2020 in ChemRxiV), designed to enhance the therapeutic activities of hydroxychloroquine by using curcumin as an adjunct drug against SARS-CoV2 receptor proteins: main-protease and S1 receptor binding domain (RBD). The webserver (ANCHOR) showed the higher protein stability for both receptors with disordered score (<0.5). The molecular docking analysis revealed that the binding energy (-24.58 kcal/mol) of hydroxychloroquine was higher than curcumin (-20.47 kcal/mol) for receptor main-protease, whereas binding energy of curcumin (-38.84 kcal/mol) had greater than hydroxychloroquine (-35.87 kcal/mol) in case of S1 receptor binding domain. Therefore, this study suggested that the curcumin could be used as combination therapy along with hydroxychloroquine for disrupting the stability of SARS-CoV2 receptor proteins.
Pharmaceutical researchers from Faculty of Pharmacy, Universitas Gadjah Mada, Indonesia, conducted molecular docking using the MOE 2010 program. The selected protein targets are RBDS (PDB ID:6LXT), PD-ACE2 (PDB ID: 6VW1), and SARS-CoV-2 protease (PDB ID:6LU7). The affinities of bonds formed is represented as a docking score. The SARS-CoV-2 virus that causes COVID-19 has important proteins used for its infection and development, namely the protease and spike glycoprotein. The RBD (Receptor Binding Domain) of spike glycoprotein (RBD-S) can bind to the ACE2 (Angiotensin Converting Enzyme-2) receptor at the protease domain (PD) (PD-ACE2) of the host cell, thereby leading to a viral infection. This study aims to reveal the potential of compounds contained in Curcuma sp., Citrus sp., Alpinia galanga, and Caesalpinia sappan as anti SARS-CoV-2 through its binding to 3 protein receptors. The results show that hesperidin, one of the compounds in Citrus sp., has the lowest docking score for all three protein receptors representing the highest affinity to bind the receptors. Moreover, all of the citrus flavonoids possess good affinity to the respected receptors as well as curcumin, brazilin, and galangin, indicating that those compounds perform inhibitory potential for the viral infection and replication. In general, the results of this study indicate that Citrus sp. exhibit the best potential as an inhibitor to the development of the SARS-CoV-2, followed by galangal, sappan wood, and Curcuma sp. that can be consumed in daily life as prophylaxis of COVID-19.
The study was published in preprints.org on 12.03.2020 (doi:10.20944/preprints202003.0214.v1)
According to article published in International Journal of Cardiology (April 6, 2020), The therapeutic time for COVID-19 infection is much longer than 14 days, but long-time viral stimulation is prone to suddenly elicit intensive immunological reactions, cytokine storm and immune-cell infiltration in vivo; however, some immunocytes especially macrophages and neutrophils can produce numerous reactive oxygen species (ROS). Generally, a certain level of ROS is important for regulating immunological responses and for clearing viruses, but excessive ROS will oxidize cellular proteins and membrane lipids and quickly destroy not only virus-infected cells but also normal cells in lung and even in heart, resulting in multiple organ failure. Thus scientists propose potential anti-oxidative therapy (Vitamin C & E and also curcumin as antioxidant) to alleviate cardiogenic casualties caused by COVID-19.
Turmeric, the golden colored strongly flavoured spice, is having a “moment.” This ancient spice, celebrated for centuries as both food and medicine, has resurfaced within the health and nutrition communities; thanks to curcumin, the healing substance which supplies its vibrant color. Turmeric is one of nature’s most powerful healers. As mentioned above list of turmeric research worldwide happening against COVID-19 issue, propose that turmeric as “the Golden Wonder Herb”
According to Chapter “Turmeric, the Golden Spice” From Traditional Medicine to Modern Medicine published in Book (Herbal Medicine: Biomolecular and Clinical Aspects. 2nd edition), in Sanskrit, turmeric has at least 53 different names. I have listed those below and pretty interesting to go through them once
In Sanskrit, turmeric has at least 53 different names, including anestha (not offered for sacrifice or homa), bhadra (auspicious or lucky), bahula (plenty), dhirgharaja (long in appearance), gandhaplashika (which produces good smell), gauri (to make fair), gharshani (to rub), haldi (that draws attention to its bright color), haridra (dear to hari, Lord Krishna), harita (greenish), hemaragi (exhibits golden color), hemaragini (gives the golden color), hridayavilasini (gives delight to heart, charming), jayanti (one that wins over diseases), jawarantika (which cures fevers), kanchani (exhibits golden color), kaveri (harlot), krimighni or kashpa (killer of worms), kshamata (capability), laxmi (prosperity), mangalprada (who bestows auspiciousness), mangalya (auspicious), mehagni (killer of fat), nisha (night), nishakhya (known as night), nishawa (clears darkness and imparts color), patwaluka (perfumed powder), pavitra (holy), pinga (reddish-brown), pinja (yellow-red powder), pita (yellow), pitika (which gives yellow color), rabhangavasa (which dissolves fat), ranjani (which gives color), ratrimanika (as beautiful as moonlight), shifa (fibrous root), shobhna (brilliant color), shiva (gracious), shyama (dark colored), soubhagaya (lucky), survana (golden color), survanavara (which exhibits golden color), tamasini (beautiful as night), umavara (Parvati, wife of Lord Shiva), vairagi (who remains free from desires), varavarnini (which gives fair complexion), varna datri (enhancer of body complexion), varnini (which gives color), vishagni (killer of poison), yamini (night), yoshitapriya (beloved of wife), and yuvati (young girl).
