The cases of COVID-19 are still increasing day-by-day worldwide, even after a year of its first occurrence in Wuhan city of China. The spreading of SARS-CoV-2 infection is very fast and different from other SARS-CoV infections possibly due to structural differences in S proteins. The patients with severe diseases may die due to acute respiratory distress syndrome (ARDS) caused by systemic inflammatory reactions due to the excessive release of pro-inflammatory cytokines and chemokines by the immune effector cells. In India too, it is spreading very rapidly, although the case fatality rate is below 1.50% (https://www.statista.com), which is markedly less than in other countries, despite the dense population and minimal health infrastructure in rural areas. This may be due to the routine use of many immunomodulator medicinal plants and traditional AYUSH formulations by the Indian people. This communication reviews the AYUSH recommended formulations and their ingredients, routinely used medicinal plants and formulations by Indian population as well as other promising Indian medicinal plants, which can be tested against COVID-19. Special emphasis is placed on Indian medicinal plants reported for antiviral, immunomodulatory and anti-allergic/anti-inflammatory activities and they are categorized for prioritization in research on the basis of earlier reports. The traditional AYUSH medicines currently under clinical trials against COVID-19 are also discussed as well as furtherance of pre-clinical and clinical testing of the potential traditional medicines against COVID-19 and SARS-CoV-2. The results of the clinical studies on AYUSH drugs will guide the policymakers from the AYUSH systems of medicines to maneuver their policies for public health, provide information to the global scientific community and could form a platform for collaborative studies at national and global levels. It is thereby suggested that promising AYUSH formulations and Indian medicinal plants must be investigated on a priority basis to solve the current crisis.

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Indian Medicinal Plants and Formulations and Their Potential Against COVID-19-Preclinical and Clinical Research

Withania somnifera is an important medicinal herb that has been widely used for the treatment of differentclinical conditions. The overall medicinal properties of Withania somnifera make it a viable therapeutic agentfor addressing anxiety, cancer, microbial infection, immunomodulation, and neurodegenerative disorders. Biochemicalconstituents of Withania somnifera like withanolideA, withanolide D, withaferin A and withaniamidesplay an important role in its pharmacological properties. Proteins like Withania somnifera glycoprotein and withanialectin like-protein possess potent therapeutic properties like antimicrobial, anti-snake venom poison and antimicrobial.In this review, we have tried to present different pharmacological properties associated with different extractpreparations, phytochemical constituents and protein component of Withania somnifera. Future insights in thisdirection have also been highlighted.

Unique Medicinal Properties of Withania somnifera: Phytochemical Constituents and Protein Component

Withania somnifera commonly known as Ashwagandha in India is used in many herbal formulations to treat various cardiovascular diseases. The key metabolite of this plant, Withaferin A was analyzed for its molecular mechanism through docking studies on different targets of cardiovascular disease. Six receptor proteins associated with cardiovascular disease were selected and interaction studies were performed with Withaferin A using AutoDock Vina. CORINA was used to model the small molecules and HBAT to compute the hydrogen bonding. Among the six targets, β1- adrenergic receptors, HMG-CoA and Angiotensinogen-converting enzyme showed significant interaction with Withaferin A. Pharmacophore modeling was done using PharmaGist to understand the pharmacophoric potential of Withaferin A. Clustering of Withaferin A with different existing drug molecules for cardiovascular disease was performed with ChemMine based on structural similarity and physicochemical properties. The ability of natural active component, Withaferin A to interact with different receptors associated with cardiovascular disease was elucidated with various modeling techniques. These studies conclusively revealed Withaferin A as a potent lead compound against multiple targets associated with cardiovascular disease.

Interaction Studies of Withania Somnifera's Key Metabolite Withaferin A with Different Receptors Assoociated with Cardiovascular Disease.

Visceral leishmaniasis (VL) is a vector-borne parasitic disease targeting tissue macrophages. It is among the most neglected infectious diseases. As available therapeutics for treatment of this disease have many side effects, there is a need for safer alternatives. One of the immunopathological consequences of active visceral leishmaniasis is suppression of protective T-helper (Th)-1 cells and induction of disease-promoting Th-2 cells, and thus the treatment of VL relies on immunomodulation. In the current study, herbal drugs derived as whole-plant extracts of Asparagus racemosus and Withania somnifera were used to treat Leishmania donovani-infected BALB/c mice. Keeping the scenario of immunosuppression during VL in mind, the potential of these drugs in the restoration of murine Th-1-type protective immune responses was evaluated. To investigate the propensity of these drugs to treat VL, liver parasite load, delayed-type hypersensitivity responses and parasite-specific immunoglobulin levels were studied. Various biochemical and haematological tests were also carried out. A positive-control group used the standard drug treatment of sodium stibogluconate. Treatment of infected mice with A. racemosus and W. somnifera in combination at the higher dose of 200 mg (kg body weight)−1 not only resulted in a successful reduction in parasite load but also generated protective Th1-type immune responses with normalization of biochemical and haematological parameters, suggesting their potential as potent anti-leishmanial agents.

Protection against experimental visceral leishmaniasis by immunostimulation with herbal drugs derived from Withania somnifera and Asparagus racemosus.

A comprehensive phytochemical, ethnomedicinal, pharmacological ecology and conservation status of Picrorhiza kurroa Royle ex Benth.: An endangered Himalayan medicinal plant

M. Mairaj Sid

Papers

Immunomodulatory Effect of Withania somnifera, Asparagus racemosus and Picrorhiza kurroa Roots