In 1960, coronaviruses belonged to the Coronaviridae family where “enveloped positive sense single-stranded ribonucleic acid (RNA) viruses” were described. Corona is derived from Latin, it signifies “crown” or “halo”, has a unique “appearance under two-dimensional transmission electron microscopy” and appears to have club-mold spike peplomers covering their surfaces. Within the Coronaviridae subfamily, α and β coronaviruses are transmitted to people. The β coronavirus strain originated from a “bat species (Rousettus leschenaultii)”. The β coronavirus strains are MERS-CoV, SARS CoV, and SARS-CoV-2. SARS-CoV-2, responsible for COVID-196 and identified “in December 2019 in Wuhan, China”, was declared as a pandemic by WHO in March 2020. COVID 19 clinical manifestations range from mild cold-like symptoms to severe respiratory distress leading to death. Globally, 4,088,848 people have been diagnosed with COVID-19 as of 12 May 2020. Researchers revealed that COVID-19 exists in two forms, S and L forms. The COVID-19 S strain is less virulent than the L strain and less adaptable to the human receptor and differs in their virulence due to their gene mutations (i.e., the L form is mutated). “This is due to the fast spreading virus which works by injecting its genome into the genes of another and multiplies. Therefore, it depends on other organisms for its growth and hence eliminating the disease-causing agent becomes challenging and it is becoming an important topic for research among drug developers, researchers, and scientists. Traditional medicine is playing a vital role in meeting the global healthcare needs. Siddha is a unique system of medicine, which originated from Tamil Nadu and has its origin in the Tamil language. Literally, the word “Siddha” means “established truth”. Siddha medicine is claimed to alleviate the root cause of the disease by maintaining the balance between Vatham, Pitham, and Kapam. There are several Siddha formulations, such as Kudineer, Mattirai, Choornam, Parapam, Chenduram, Karuppu, and Mezhugu. The aim of the present review is to explore some of the herbal and herbo mineral formulations used to prevent or treat COVID-19.
Siddha Formulations
The Siddha medicines chosen for the management of COVID-19 depend on its pharmacological action, which is mentioned in articles published in journals and book references that can help healthcare professionals and researchers for patient care.Adathodai Manapagu
This preparation is based on the juice of Adhatoda vasica (AV) leaf. Adhatoda vasica belongs to the Acanthaceae family. The plants contain "quinazoline alkaloids (vasicine, 7-hydroxy vasicine, vasicinone, 3-deoxy vasicine, vasicol, vascoline, vascolinone, triterpenes, anisotine), betaine, steroid carbohydrates and alkanes. In the flowers, triterpenes (a-amyrin) and flavonoids (apigenin, astragalin, kaempferol, quercetin, vitexin) have been found. Crude extract of Justicia adhatoda acts against influenza virus by reducing hemagglutination (HA). In two unique layouts of simultaneous and post-treatment, the assay shows antiviral activity in the non-cytotoxic range. Methanolic extract of A.V. adhatoda at a concentration of 10 mg/mL revealed 100% relaxation in HA simultaneously and post-treatment. The aqueous extract of J. adhatoda showed reduction of HA by 33% and 16.67%, respectively, in simultaneous assay. These results showed that the aqueous and methanolic extracts of J. adhatoda have strong antiviral activity that can inhibit viral attachment and/or viral replication, and can be used for viral prevention. The compound vasinin shows excellent antiviral properties in DOCK assay.Kabasura Kudineer
The Siddha classical formulation Kabasura Kudineer Choornam contains 15 ingredients of herbs (Zingiber officinale, Piper longum Syzygium aromaticum, Tragia involucrata, Anacyclus pyrethrum, Hygrophila auriculata, Terminalia chebula, Avea, Coleus amboinicus, Saussurea lappa, Tinospora cordifolia, Clerodendron serratum, Andrographis paniculata, Sida acuta, and Cyperus rotundus)”. The mechanism of action of the phytocompounds present in Kabasura Kudineer Siddha formulation attracts/binds to multiple amino acids at different locations of the viral protein, which matches with the well-known antimalarial drug, Artemisinin. It showed the synergistic activity of the phytocompounds to not only bind to the viral proteins but also modulate the immune system to fight against viral replication. The active molecules of the related medicinal plants, Trichosanthes cucumerina, T. cordifolia, H. auriculata, A. pyrethrum, A. paniculata, avi, S. lappa, C. serratum, S. aromaticum, and Z. officinale, can inhibit viral pathogenesis at various levels spanning from prevention to cure. It showed that the functionally significant formulations against the corona viral proteins showed more efficient inhibitory effect against viral replication.Thontha Sura Kudineer
Thontha Sura Kudineer Choornam contains 10 ingredients of herbs (Z. officinale, avi, A. paniculata, T. cordifolia, Elettaria cardamomum, Solanum xanthocarpum, T. cucumerina, Tephrosia purpurea, Mollugo cerviana, and Vitis vinifera) were studied for antiviral activity. By in silico docking analysis. The phytocompounds present in The Thontha Sura Kudineer had promising activity against the viral spike glycoprotein, which prevents the spike protein from binding with the host cell receptor. Nilavembu Kudineer (NVK) “Nilavembu Kudineer is a polyherbal formulation with A. paniculata as the main ingredient that controls all types of fevers associated with body pain. Other ingredients include Vetiveria zizanioides, V. zizanioides, Santalum album, T. cucumerina, C. rotundus, Zingiber officinale, Piper nigrum and M. cerviana. All these plants are traditionally used as antipyretics, in the treatment of “inflammations, arthritis, rheumatism, gastric ulcers, jaundice and general debilitating conditions”. Nilavembu Kudineer controls fever extensively through its management effects on temperature, inflammation control, body pain, and it also acts to improve immunity. All the components of this formulation contain bioactive molecules that show excellent activity against dengue, chikungunya, herpes simplex virus (HSV), and influenza virus.Vajra Kandi Chenduram
It is an herbal medicine used exclusively by Siddha practitioners for the management of several acute and chronic diseases ranging from fever to chronic inflammatory disorders and immune-mediated diseases. This formulation is composed of Shuddha Lingam, Veeram, Pooram and Rasa Sindhuram. The ingredients show antipyretic, anti-inflammatory and antioxidant activity. Vajra Kandi Chenduram through its antipyretic and anti-inflammatory activity may have the potential to prevent the release of inflammatory mediators and cytokine storm of COVID-19 which is a major cause of severe lung complication. Therefore, this formulation may be recommended as a safe and effective adjunctive therapy in the absence of any specific target treatment measures. Targeting key molecules within the inflammatory cytokine network, such as interleukin-6 (IL-6), is a novel strategy for COVID-19 induced “cytokine release syndrome (CRS)”. “Interleukin-6 inhibitors can ameliorate the severe damage to bronchial tissue caused by cytokine release in patients with severe COVID-19 infection. Several damages to bronchial tissue due to cytokine release are being reported in patients with severe COVID-19 infection.26 Several studies have indicated a “cytokine storm” with release of IL-6, IL-1, IL-2 and IL-8 along with 'tumor necrosis factor' α (THF α) and other inflammatory mediators.Visha Sura Kudineer
Visha Sura Kudineer (VSK) is a multi-herbal formulation from the Siddha literature "Kavya Sura Nool". The constituents were Azadirachta indica, Indigofera tinctoria, Z. officinale, Hemidesmus indicus, Aristolochia bracteata, V. zizanioides, Glycyrrhiza glabra, E. cardamomum, and Santalum album. Each constituent shows antiviral activity against wide range of viruses. "Aqueous leaf extract of A. indica provides antiviral activity against vaccinia virus, Chikungunya measles virus, dengue virus type-2 and HSV" type-1, it also has immune stimulant, anticomplement activity.32 Indigofera tinctoria shows inhibitory effect of HIV-1 (IIIb) and HIV-2.33 "Zingiber officinale has antiviral activity against human respiratory syncytial virus in human respiratory tract cell lines". Hemidesmus indicus antiviral activity was studied against Ranikhet virus. “A component of licorice root glycyrrhizic acid has antiviral activity by inhibiting the growth and cytopathic effect of several DNA and RNA viruses, such as vaccinia, HSV-1, Newcastle disease and vesicular stomatitis virus”. It also shows antiviral activity against flaviviruses such as dengue, Japanese encephalitis, yellow fever, mammalian tick-borne encephalitis, influenza and hepatitis A, B, C viruses. 34 Sandalwood oil, the essential oil of Santalum album L., shows antiviral activity against HSV-1 and HSV-2.33Management
Isolation is the best measure for prevention of COVID-19. No specific antiviral treatment or “vaccine is currently available.35 Hence, treatment of COVID-19 is associated with symptomatic care and oxygen therapy. Patients with mild infection lack early supportive management.'' However, in Siddha, this infection is adequately treated by a specific course of “treatment called a regimen. The treatment regimen used during the early days of infection includes one or more formulations namely Edathodai Manpagu, Kabasura Kudineer, Thontha Sura Kudineer, Vajra Kandi Chenduram, VSK and NVK. The dynamic active biomolecules in the above mentioned formulations act strongly against a wide range of viruses out of the six formulations, AV is common in four formulations, hence the treatment regimen should be in conjunction with Edathodai Manpagu. “However, the efficacy of corticosteroids, a commonly used anti-inflammatory agent, for treating COVID-19-induced CRS is controversial. There is an urgent need for novel therapies to treat COVID-19-induced CRS. The British Pharmacological Society has responded to concerns that the use of non-steroidal anti-inflammatory drugs (NSAIDs) may aggravate symptoms of the novel coronavirus infection, COVID-19. The World Health Organization issued a statement on March 18, 2020, that it is “aware of concerns over the use of ibuprofen for treating fever in people with COVID 19”.34 Hence at this time, the use of proven anti-inflammatory, antipyretic and immune-modulatory agents can provide immense help in the management of CRS. Vajra Kandi Chendooram shows all this activity; hence, it can be replaced with corticosteroids. Thereby Siddha medicines can assist in the next phase in the prevention of Phase-I coronavirus and prevent morbidity and mortality of COVID-19 patients. Hence, these medicines are safe to be administered at the prescribed dosage under the medical supervision of a Siddha doctor. Moreover, all the ingredients have been toxicologically tested and are safe for humans. Hence, the above Siddha formulation can be considered for public use during this global pandemic.Conclusion
“COVID-19 is spreading at a disturbing rate across the world. It has caused more infections and spread than SARS or MERS. The rapid spread of infection allows for extraordinary surveillance and quarantine protocols to prevent further transmission. No confirmed treatment or vaccination has been developed. Current treatment techniques are focused on indicative consideration oxygen treatment. Through this review work, all the ingredients of Siddha formulation have been scientifically explored for its pharmacological actions, toxicity evaluation, and are safe for humans. Further preclinical studies on the antiviral actions of the proven formulation may be required to scientifically confirm our hypothesis and are planned to be performed soon.
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AYURVEDIC MEDICINES
