COVID-19 pandemic: A pragmatic plan for ayurveda intervention.

Editor’s Note: National governments are deeply divided over whether traditional, complementary and integrative practices have value for human beings relative to COVID-19. We witness a double standard. Medical doctors explore off-label uses of pharmaceutical agents that may have some suggestive research while evidence that indicates potential utility of natural products, practices and practitioners is often dismissed. In this Invited Commentary, a long-time JACM Editorial Board member Bhushan Patwardhan, PhD, from the AYUSH Center of Excellence, Center for Complementary and Integrative Health at the Savitribai Phule Pune University, India and colleagues from multiple institutions make a case for the potential roles of Ayurvedic medicine and Yoga as supportive measures in self-care and treatment. Patwardhan is a warrior for enhancing scientific standards in traditional medicine in India. Patwardhan was recently appointed by the Ministry of AYUSH, Government of India, as Chairman of an 18 member expert group known as ‘‘Interdisciplinary AYUSH Research and Development Taskforce’’ for initiating, coordinating and monitoring efforts against COVID-19. He was last seen here in an invited commentary entitled ‘‘Contesting Predators: Cleaning Up Trash in Science’’ (JACM, October 2019). We are pleased to have this opportunity to share the recommended approaches, the science, and the historic references as part of the global effort to leave no stone unturned in best preparing our populations to withstand COVID-19 and future viral threats. – John Weeks, Editor-in-Chief, JACM (johnweeks-integrator.com)

Public Health Approach of Ayurveda and Yoga for COVID-19 Prophylaxis.

COVID-19 has ravaged the world and is the greatest of pandemics in modern human history, in the absence of treatment or vaccine, the mortality and morbidity rates are very high The present investigation identifies potential leads from the plant Withania somnifera (Indian ginseng), a well-known antiviral, immunomodulatory, anti-inflammatory and a potent antioxidant plant, using molecular docking and dynamics studies Two different protein targets of SARS-CoV-2 namely NSP15 endoribonuclease and receptor binding domain of prefusion spike protein from SARS-CoV-2 were targeted Molecular docking studies suggested Withanoside X and Quercetin glucoside from W somnifera have favorable interactions at the binding site of selected proteins, that is, 6W01 and 6M0J The top-ranked phytochemicals from docking studies, subjected to 100 ns molecular dynamics (MD) suggested Withanoside X with the highest binding free energy (ΔGbind = -8942 kcal/mol) as the most promising inhibitor During MD studies, the molecule optimizes its conformation for better fitting with the receptor active site justifying the high binding affinity Based on proven therapeutic, that is, immunomodulatory, antioxidant and anti-inflammatory roles and plausible potential against n-CoV-2 proteins, Indian ginseng could be one of the alternatives as an antiviral agent in the treatment of COVID 19 Communicated by Ramaswamy H Sarma

Sars-cov-2 host entry and replication inhibitors from Indian ginseng: an in-silico approach.

COVID-19 has ravaged the world and is the greatest of pandemics in human history, in the absence of treatment or vaccine the mortality and morbidity rates are very high The present investigation was undertaken to screen and identify the potent leads from the Indian Ayurvedic herb, Asparagus racemosus (Willd) against SARS-CoV-2 using molecular docking and dynamics studies The docking analysis was performed on the Glide module of Schrodinger suite on two different proteins from SARS-CoV-2 viz NSP15 Endoribonuclease and spike receptor-binding domain Asparoside-C, Asparoside-D and Asparoside -F were found to be most effective against both the proteins as confirmed through their docking score and affinity Further, the 100 ns molecular dynamics study also confirmed the potential of these compounds from reasonably lower root mean square deviations and better stabilization of Asparoside-C and Asparoside-F in spike receptor-binding domain and NSP15 Endoribonuclease respectively MM-GBSA based binding free energy calculations also suggest the most favourable binding affinities of Asparoside-C and Asparoside-F with binding energies of -6261 and -5519 Kcal/mol respectively with spike receptor-binding domain and NSP15 Endoribonuclease HighlightsAsparagus racemosus have antiviral potentialPhytochemicals of Shatavari showed promising in-silico docking and MD resultsAsparaoside-C and Asparoside-F has good binding with target proteinsAsparagus racemosus holds promise as SARS-COV-2 (S) and (N) proteins inhibitor Communicated by Ramaswamy H Sarma

In-silico investigation of phytochemicals from Asparagus racemosus as plausible antiviral agent in COVID-19.

COVID-19 pandemic: A pragmatic plan for ayurveda intervention

The Coronavirus disease (COVID-19) caused by the virus SARS-CoV-2 has become a global pandemic in a very short time span. Currently, there is no specific treatment or vaccine to counter this highly contagious disease. There is an urgent need to find a specific cure for the disease and global efforts are directed at developing SARS-CoV-2 specific antivirals and immunomodulators. Ayurvedic Rasayana therapy has been traditionally used in India for its immunomodulatory and adaptogenic effects, and more recently has been included as therapeutic adjuvant for several maladies. Amongst several others, Withania somnifera (Ashwagandha), Tinospora cordifolia (Guduchi) and Asparagus racemosus (Shatavari) play an important role in Rasayana therapy. The objective of this study was to explore the immunomodulatory and anti SARS-CoV2 potential of phytoconstituents from Ashwagandha, Guduchi and Shatavari using network pharmacology and docking. The plant extracts were prepared as per ayurvedic procedures and a total of 31 phytoconstituents were identified using UHPLC-PDA and mass spectrometry studies. To assess the immunomodulatory potential of these phytoconstituents an in-silico network pharmacology model was constructed. The model predicts that the phytoconstituents possess the potential to modulate several targets in immune pathways potentially providing a protective role. To explore if these phytoconstituents also possess antiviral activity, docking was performed with the Spike protein, Main Protease and RNA dependent RNA polymerase of the virus. Interestingly, several phytoconstituents are predicted to possess good affinity for the three targets, suggesting their application for the termination of viral life cycle. Further, predictive tools indicate that there would not be adverse herb-drug pharmacokinetic-pharmacodynamic interactions with concomitantly administered drug therapy. We thus make a compelling case to evaluate the potential of these Rasayana botanicals as therapeutic adjuvants in the management of COVID-19 following rigorous experimental validation.

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Ayurveda botanicals in COVID-19 management: An in silico multi-target approach.

As the COVID-19 pandemic is progressing, the therapeutic gaps in conventional management have highlighted the need for the integration of traditional knowledge systems with modern medicine. Ayurvedic medicines, especially Ashwagandha (Withania somnifera (L.) Dunal, WS), may be beneficial in the management of COVID-19. WS is a widely prescribed Ayurvedic botanical known as an immunomodulatory, antiviral, anti-inflammatory, and adaptogenic agent. The chemical profile and pharmacological activities of WS have been extensively reported. Several clinical studies have reported its safety for use in humans. This review presents a research synthesis of in silico, in vitro, in vivo, and clinical studies on Withania somnifera (L.) Dunal (WS) and discusses its potential for prophylaxis and management of COVID-19. We have collated the data from studies on WS that focused on viral infections (HIV, HSV, H1N1 influenza, etc.) and noncommunicable diseases (hypertension, diabetes, cancer, etc.). The experimental literature indicates that WS has the potential for 1) maintaining immune homeostasis, 2) regulating inflammation, 3) suppressing pro-inflammatory cytokines, 4) organ protection (nervous system, heart, lung, liver, and kidney), and 5) anti-stress, antihypertensive, and antidiabetic activities. Using these trends, the review presents a triangulation of Ayurveda wisdom, pharmacological properties, and COVID-19 pathophysiology ranging from viral entry to end-stage acute respiratory distress syndrome (ARDS). The review proposes WS as a potential therapeutic adjuvant for various stages of COVID-19 management. WS may also have beneficial effects on comorbidities associated with the COVID-19. However, systematic studies are needed to realize the potential of WS for improving clinical outcome of patients with COVID-19.

/pdf/withania-somnifera-l-dunal-opportunity-for-clinical-3ncd3q0n4a.pdf

Withania somnifera (L.) Dunal: Opportunity for Clinical Repurposing in COVID-19 Management

This paper discusses the potential of Ayurveda rasayana in prophylaxis of COVID-19. Scientific evidence based on research spanning over 25 years indicates that Ayurveda rasayana such as Ashwagandha (Withania somnifera;WS) can be a potential candidate for management of COVID-19. Ashwagandha can offer multi-target effects in inflammatory conditions by restoring immune homeostasis. Possible role and immune targets of ashwagandha in prophylaxis of COVID-19 are shown. It is suggested that, under current exceptional circumstances, interdisciplinary research on evidence-based Ayurveda interventions should be prioritized with an open mind for prophylaxis and add-on treatment of SARSCoV-2 infection.

Ayurveda rasayana in prophylaxis of COVID-19

Withania somnifera (L.) Dunal: A potential therapeutic adjuvant in cancer.

Neurotrophins (NT) are a closely related family of growth factors, which regulate the nervous system's development, maintenance, and function. Although NTs have been well studied in neuronal cells, they are also expressed in the placenta. Despite their suggested role in regulating fetoplacental development, their precise functional significance in the placenta remains elusive. NT activate two different classes of receptors. These include the Trk, tropomyosin-related kinase family of high-affinity tropomyosin-related kinase receptors, which induces cell survival, and the p75NTR, p75 neurotrophin receptor, a member of the tumor necrosis factor(TNF) receptor superfamily, which induces apoptosis in neuronal cells. Mature NT molecule results from proteolysis of a biologically active precursor form called pro-neurotrophins (pro-NT) by the intracellular proprotein convertase or furin. Pro-NTs have a regulatory role in determining cell survival and apoptosis. Here, we review the literature on the expression and functions of NTs and their receptors in the placenta and discuss their possible role in placental tissue development and apoptosis. The possible implications of imbalance in pro-NT and mature-NT levels for fetoplacental development are also discussed.Abbreviations AGE/ALEs: Advanced glycation/lipoxidation end products; Bax: Bcl 2 Associated X; Bcl-2: B-cell lymphoma 2; BDNF: Brain-derived neurotrophic factor; FAS/FASL: Fas cell surface death receptor/ ligand; IUGR: Intrauterine growth restriction; JNK: c-Jun amino-terminal kinase; MAP: mitogen-activated protein k; mRNA: Messenger ribonucleic acid; NGF: Nerve growth factor; NT: Neurotrophins; NRAGE: Neurotrophin receptor-interacting MAGE homolog; NRIF: Neurotrophin receptor interacting factor; PE: Preeclampsia; PI3k: Phosphoinositide 3- kinase; PLC: Phospholipase C; p75NTR: p75 neurotrophin receptor; Pro-NT: Pro-neurotrophins; PTB: Preterm birth; p53: Tumor protein p53; TNF: Tumor necrosis factor; TRAF: TNFR-associated factors; Trk: Tropomyosin-related kinase; siRNA: small interfering ribonucleic acid.

Preeti Chavan-Gautam

Papers

Ayurveda botanicals in COVID-19 management: An in silico multi-target approach.

Withania somnifera (L.) Dunal: Opportunity for Clinical Repurposing in COVID-19 Management

Ayurveda rasayana in prophylaxis of COVID-19

Withania somnifera (L.) Dunal: A potential therapeutic adjuvant in cancer.

The balance between cell survival and death in the placenta: Do neurotrophins have a role?