Phytochemicals of Withania somnifera as a Future Promising Drug against SARS-CoV-2: Pharmacological Role, Molecular Mechanism, Molecular Docking Evaluation, and Efficient Delivery.

Coronavirus disease (COVID-19) has killed millions of people since first reported in Wuhan, China, in December 2019. Intriguingly, Withania somnifera (WS) has shown promising antiviral effects against numerous viral infections, including SARS-CoV and SARS-CoV-2, which are contributed by its phytochemicals. This review focused on the updated testing of therapeutic efficacy and associated molecular mechanisms of WS extracts and their phytochemicals against SARS-CoV-2 infection in preclinical and clinical studies with the aim to develop a long-term solution against COVID-19. It also deciphered the current use of the in silico molecular docking approach in developing potential inhibitors from WS targeting SARS-CoV-2 and host cell receptors that may aid the development of targeted therapy against SARS-CoV-2 ranging from prior to viral entry until acute respiratory distress syndrome (ARDS). This review also discussed nanoformulations or nanocarriers in achieving effective WS delivery to enhance its bioavailability and therapeutic efficacy, consequently preventing the emergence of drug resistance, and eventually therapeutic failure.

Pharmacological potential of Withania somnifera (L.) Dunal and Tinospora cordifolia (Willd.) Miers on the experimental models of COVID-19, T cell differentiation, and neutrophil functions.

Cytokine release syndrome (CRS) due to severe acute respiratory coronavirus-2 (SARS-CoV-2) infection leads to life-threatening pneumonia which has been associated with coronavirus disease (COVID-19) pathologies. Centuries-old Asian traditional medicines such as Withania somnifera (L.) Dunal (WS) and Tinospora cordifolia (Willd.) Miers (TC) possess potent immunomodulatory effects and were used by the AYUSH ministry, in India during the COVID-19 pandemic. In the present study, we investigated WS and TC's anti-viral and immunomodulatory efficacy at the human equivalent doses using suitable in vitro and in vivo models. While both WS and TC showed immuno-modulatory potential, WS showed robust protection against loss in body weight, viral load, and pulmonary pathology in the hamster model of SARS-CoV2. In vitro pretreatment of mice and human neutrophils with WS and TC had no adverse effect on PMA, calcium ionophore, and TRLM-induced ROS generation, phagocytosis, bactericidal activity, and NETs formation. Interestingly, WS significantly suppressed the pro-inflammatory cytokines-induced Th1, Th2, and Th17 differentiation. We also used hACE2 transgenic mice to further investigate the efficacy of WS against acute SARS-CoV2 infection. Prophylactic treatment of WS in the hACE2 mice model showed significant protection against body weight loss, inflammation, and the lung viral load. The results obtained indicate that WS promoted the immunosuppressive environment in the hamster and hACE2 transgenic mice models and limited the worsening of the disease by reducing inflammation, suggesting that WS might be useful against other acute viral infections. The present study thus provides pre-clinical efficacy data to demonstrate a robust protective effect of WS against COVID-19 through its broader immunomodulatory activity.

The Impact of Ashwagandha on Stress, Sleep Quality, and Food Cravings in College Students: Quantitative Analysis of a Double-Blind Randomized Control Trial.

The purpose of this study was to examine the impact of ashwagandha (ASH) (Withania somnifera) on sleep, perceived stress, and cravings in a college student population. Sixty healthy students were screened/enrolled into a 30-day double-blinded placebo (PLA)-controlled intervention (700 mg daily, full spectrum extract of ASH root). Anthropometrics, demographics, and validated questionnaires assessing physical activity, restorative sleep, perceived stress, and food cravings were assessed before and after the study. Descriptive statistics, Pearson's correlations, and point biserial correlations were used to screen the data. For sleep and stress, a nonsignificant mixed (group × time) multivariate analysis of variance (MANOVA) was followed by one-way MANOVA (time on sleep/stress) and one-way multivariate analysis of covariance (MANCOVA) (group on sleep/stress, using initial sleep as a covariate) as follow-up tests. Further follow-up tests for this MANCOVA showed group membership affected final sleep (58.4 ± 12.4 vs. 48.2 ± 15.0 ASH vs. PLA respectively, P < .05) using initial sleep as a covariate. Initial sleep (confounder) affected final stress, but not final sleep. Mixed analysis of variance (group × time) showed an interaction effect on food cravings, where the ASH group experienced lower cravings than the PLA group over time at end of study. The 30-day intervention was shorter than most other studies where more pronounced stress differences were seen at six weeks, indicating ASH may need the longer time period to show more pronounced stress relieving differences. ASH can be an effective safe intervention in young adult populations to help manage stress and its detrimental impacts on sleep and satiety in as little as 30 days. Clinical Trial Registration number-NCT05430685.

Withania somnifera (L.) Dunal (Ashwagandha) for the possible therapeutics and clinical management of SARS-CoV-2 infection: Plant-based drug discovery and targeted therapy.

Coronavirus disease 2019 (COVID-19) pandemic has killed huge populations throughout the world and acts as a high-risk factor for elderly and young immune-suppressed patients. There is a critical need to build up secure, reliable, and efficient drugs against to the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Bioactive compounds of Ashwagandha [Withania somnifera (L.) Dunal] may implicate as herbal medicine for the management and treatment of patients infected by SARS-CoV-2 infection. The aim of the current work is to update the knowledge of SARS-CoV-2 infection and information about the implication of various compounds of medicinal plant Withania somnifera with minimum side effects on the patients' organs. The herbal medicine Withania somnifera has an excellent antiviral activity that could be implicated in the management and treatment of flu and flu-like diseases connected with SARS-CoV-2. The analysis was performed by systematically re-evaluating the published articles related to the infection of SARS-CoV-2 and the herbal medicine Withania somnifera. In the current review, we have provided the important information and data of various bioactive compounds of Withania somnifera such as Withanoside V, Withanone, Somniferine, and some other compounds, which can possibly help in the management and treatment of SARS-CoV-2 infection. Withania somnifera has proved its potential for maintaining immune homeostasis of the body, inflammation regulation, pro-inflammatory cytokines suppression, protection of multiple organs, anti-viral, anti-stress, and anti-hypertensive properties. Withanoside V has the potential to inhibit the main proteases (Mpro) of SARS-CoV-2. At present, synthetic adjuvant vaccines are used against COVID-19. Available information showed the antiviral activity in Withanoside V of Withania somnifera, which may explore as herbal medicine against to SARS-CoV-2 infection after standardization of parameters of drug development and formulation in near future.

An Insight of Clinical Evidence of Ayurveda Interventions in the Management of COVID-19 Patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) was caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and patients with COVID-19 may be treated with traditional medicine like Ayurveda alone or in combination with standard allopathic treatment, as Ayurveda is one of the oldest traditional medicinal systems followed by millions around the world. METHODS: The literature was searched in databases such as LitCOVID, Google Scholar, Science Direct, EBSCO, Scopus, Web of Science, EMBASE, and reference lists to identify articles relevant to the use of Ayurvedic medicines in the management of COVID-19. RESULTS: Several clinical studies have determined the efficacy of Ayurvedic medicines and formulations in the management of patients with COVID-19. CONCLUSION: The Ayurvedic medicines and formulations with antiviral, antioxidant, anti-inflammatory, and immunomodulatory properties could be used along with standard allopathic medicines to assist in the earlier detection of virus, speedy recovery of patients with COVID-19, faster discharge from hospitals, and the prevention of further deterioration.

Herbal Drugs as Immune Booster Against Viral Infections

The immune system involves both active and passive immunization. The antibodies are developed against the antigens during active immunization and are permanently stored. But, in the case of passive immunization, the antibodies are exposed to the same antigens in every person who is already infected. In order to enhance the immune systems i.e. innate and adaptive immune responses, herbal plants are used as an immune booster. Some of the herbal plants have been proven clinically to enhance immunity that includes Morniga oleifera (Drumstick), Azadirachta indica (Neem), Ocimum sanctum (Tulsi), Withania somnifera (Aswagandha), Zingiber officinale (Ginger), Allium sativum (Garlic), Curcuma longa (Turmeric), Emblica officinalis (Amla) etc. Compared to synthetic drugs, herbal drugs have fewer side effects and stimulate the immune system to defend against various foreign pathogens. Even though herbal medicines are usually considered as safe and effective therapy, it is clinically proven that if a drug is effective, it would have some side effects. But, sometimes, the antioxidant property of herbal medicines is helpful in reducing the toxicities produced by any toxic substances or any drugs. This review aims to encourage the study of various herbal constituents and their role in the treatment of different types of viral infections.

Corrigendum: Randomized, Double Blind, Placebo Controlled, Clinical Trial to Study Ashwagandha Administration in Participants Vaccinated Against COVID-19 on Safety, Immunogenicity, and Protection With COVID-19 Vaccine-A Study Protocol.

[This corrects the article DOI: 10.3389/fmed.2022.761655.].

Technical Note: Negative Interference of Ashwagandha, an Indian Ayurveda Medicine Indicated for Preventing COVID-19, in IL-6 Immunoassay.

OBJECTIVE: Ashwagandha, an Indian Ayurvedic medicine is indicated to prevent COVID-19 infection. Because IL-6 and C-reactive protein are widely measured to determine risk of cytokine storm in hospitalized COVID-19 patients, we studied potential interference of ashwagandha on these two assays. Previous studies indicated that ashwagandha may interfere with digoxin assay, so we also studied potential interference with digoxin assay. MATERIALS AND METHODS: We obtained one ashwagandha product from India (liquid extract) and one product from US (Herb Pharma; liquid extract). We prepared two serum pool each for IL-6, C-reactive protein and digoxin by combining appropriate left-over specimens submitted to our hospital laboratory for such tests. Then aliquots of each pools were supplemented with 10, 25 or 50 µL of ashwagandha extract followed by re-analysis for appropriate analyte and comparing values with original pool. RESULTS: We observed negative interference of ashwagandha with IL-6 assay only (Indian product showed more negative interference) but C-reactive protein assay and digoxin assay were not affected. Negative interference of ashwagandha in IL-6 assay has not been reported before. CONCLUSION: We conclude ashwagandha caused negative interference in IL-6 assay.

Randomized, Double Blind, Placebo Controlled, Clinical Trial to Study Ashwagandha Administration in Participants Vaccinated Against COVID-19 on Safety, Immunogenicity, and Protection With COVID-19 Vaccine-A Study Protocol.

INTRODUCTION: Vaccines have emerged as the most effective tool in the fight against COVID-19. Governments all over the world have rolled out the COVID-19 vaccine program for their populations. Oxford-AstraZeneca COVID-19 vaccine (COVISHIELD™) is widely used in India. A large number of Indian people have been consuming various traditional medicines in the hope of better protection against COVID-19 infection. Several studies have reported immunological benefits of Withania somnifera (Ashwagandha) and its potential as a vaccine adjuvant. We propose to study the safety, immunogenicity and clinical protection offered by a 6-month regimen of Ashwagandha in participants who volunteer to be vaccinated against COVID-19 (COVISHIELDTM) in the ongoing national program of vaccination. METHODS AND ANALYSIS: We designed a prospective, randomized, double-blind, parallel-group, placebo-controlled, two-arm, exploratory study on healthy volunteers receiving the COVISHIELDTM vaccine. The administration of Ashwagandha will begin within 7 days of the first or second dose of COVISHIELDTM. Primary outcome measure is immunogenicity as measured by SARS-CoV-2 spike (S1) and RBD-specific IgG antibody titres. Secondary outcome measures are safety, protective immune response and quality of life measures. All adverse events will be monitored at each time throughout the study. Participants will be tracked on a daily basis with a user-friendly mobile phone application. Following power calculation 600 participants will be recruited per arm to demonstrate superiority by a margin of 7% with 80% power. Study duration is 28 weeks with interim analysis at the end of 12 weeks. ETHICS AND DISSEMINATION: Ethics approval was obtained through the Central and Institutional Ethics Committees. Participant recruitment commenced in December 2021. Results will be presented in conferences and published in preprints followed by peer-reviewed medical journals. CLINICAL TRIAL REGISTRATION: [www.ClinicalTrials.gov], identifier [CTRI/2021/06/034496].

Identification of bioactive molecule from Withania somnifera (Ashwagandha) as SARS-CoV-2 main protease inhibitor.

SARS-CoV-2 is the causative agent of COVID-19 and has been declared as pandemic disease by World Health Organization. Lack of targeted therapeutics and vaccines for COVID-2019 have triggered the scientific community to develop new vaccines or drugs against this novel virus. Many synthetic compounds and antimalarial drugs are undergoing clinical trials. The traditional medical practitioners widely use Indian medicinal plant Withania somnifera (Ashwagandha) natural constituents, called withanolides for curing various diseases. The main protease (Mpro) of SARS-CoV-2 plays a vital role in disease propagation by processing the polyproteins which are required for its replication. Hence, it denotes a significant target for drug discovery. In the present study, we evaluate the potential of 40 natural chemical constituents of Ashwagandha to explore a possible inhibitor against main protease of SARS-CoV-2 by adopting the computational approach. The docking study revealed that four constituents of Ashwagandha; Withanoside II (-11.30 Kcal/mol), Withanoside IV (-11.02 Kcal/mol), Withanoside V (-8.96 Kcal/mol) and Sitoindoside IX (-8.37 Kcal/mol) exhibited the highest docking energy among the selected natural constituents. Further, MD simulation study of 100 ns predicts Withanoside V possess strong binding affinity and hydrogen-bonding interactions with the protein active site and indicates its stability in the active site. The binding free energy score also correlates with the highest score of -87.01 ± 5.01 Kcal/mol as compared to other selected compounds. In conclusion, our study suggests that Withanoside V in Ashwagandha may be serve as a potential inhibitor against Mpro of SARS-CoV-2 to combat COVID-19 and may have an antiviral effect on nCoV.Communicated by Ramaswamy H. Sarma.

Withania somnifera as a safer option to hydroxychloroquine in the chemoprophylaxis of COVID-19: Results of interim analysis.

OBJECTIVES: To study the efficacy and safety of Withania somnifera (WS, Ashwagandha) in the prophylaxis against COVID-19 in high risk health care workers (HCW) in comparison to hydroxychloroquine (HCQ). To evaluate the general physical and mental health benefits of Ashwagandha. METHODS: A 16 week randomized prospective, open-label, parallel efficacy, two arm, multi-centre study. The primary efficacy measure was 'failure of prophylaxis' as confirmed COVID-19 by quantitative Reverse Transcription Polymerase Chain Reaction (RT-PCR) at any time during the study period. This study on 400 participants from three centres was designed to establish non-inferiority for WS to HCQ for prophylaxis against COVID-19 at 80 % power and significance p < 0.025, one-sided. The interim analysis was carried out on 160 participants after completion of 8 weeks. RESULTS: Participants in both the arms were well-matched at the baseline characteristics. Forty participants in the HCQ group and 26 participants in the WS group reported mild AE. The symptoms of confirmed COVID-19 were found to be 3.7 % (95 % CI 1.3-10.5 %) in the HCQ and 1.3 % (95 % CI 0.02-6.7 %) in the WS arm amongst the first 160 participants completing 8 weeks. CONCLUSION: Our intent was to explore a safer option to HCQ. We report that WS was not found inferior to HCQ and its efficacy was within the 15 % non-inferiority margin set a priori. WS as an immunomodulator has other clinical benefits including reducing mental stress. The final report of this study is expected by end of August 2021.

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 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 = -89.42 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.

Safety and efficacy of Ayurvedic interventions and Yoga on long term effects of COVID-19: A structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: Primary Objective • To assess the efficacy of Ayurveda interventions and Yoga in rehabilitation of COVID-19 cases suffering with long term effects of COVID 19 as compared to WHO Rehabilitation Self-Management after COVID-19- Related Illness. Secondary Objective • To assess the safety of Ayurvedic interventions in cases suffering with long term effects of COVID 19 TRIAL DESIGN: Multi-centric, randomized, controlled, parallel group, open-label, exploratory study. The study duration is 9 months and the intervention period is 90 days from the day of enrolment of the participant. PARTICIPANTS: Patients of either sex between 18 to 60 years, ambulatory, willing to participate, with history (not more than 4 weeks) of positive RT-PCR for COVID-19 or IgM antibodies positivity for SARS CoV-2, but having negative RT-PCR for COVID-19 at the time of screening will be considered eligible for enrolment in the study. Critically ill patients with ARDS (acute respiratory distress syndrome), requiring invasive respiratory support in the intensive care unit, known case of any malignancy, immune-compromised state (e.g. HIV), diabetes mellitus, active pulmonary tuberculosis, past history of any chronic respiratory disease, motor neuron disease, multiple sclerosis, stroke, impaired cognition, atrial fibrillation, acute coronary syndrome, myocardial infarction, severe arrhythmia, concurrent serious hepatic disease or renal disease, pregnant or lactating women, patients on immunosuppressive medications, history of hypersensitivity to the trial drugs or their ingredients, depressive illness (before COVID-19), diagnosed psychotic illnesses, substance dependence or alcoholism will be excluded. The trial will be conducted at two medical colleges in Maharashtra, India. INTERVENTION AND COMPARATOR: Intervention Arm (Group-I): Ayurveda interventions including Agastya Haritaki six gram and Ashwagandha tablet 500 mg twice daily orally after meals with warm water and two sessions of yoga (morning 30 minutes and evening 15 minutes) daily for 90 days, as per the post-COVID-19 care protocol provided in National Clinical Management Protocol based on Ayurveda and Yoga for management of COVID-19 published by Ministry of AYUSH, Government of India. Comparator Arm (Group-II): WHO Rehabilitation Self-Management after COVID-19 related illness for 90 days. The trial drugs are being procured from a GMP certified pharmaceutical company. MAIN OUTCOMES: Primary Outcome: Change in respiratory function to be assessed by San Diego shortness of breath Questionnaire, 6-minutes walk test and pulmonary function test. SECONDARY OUTCOMES: Change in High-resolution Computed Tomography (HRCT) Chest Change in Fatigue score assessed by Modified Fatigue Impact Scale Change in Anxiety score assessed by Hospital Anxiety and Depression Scale Score Change in Sleep Quality assessed by Pittsburgh Sleep Quality Index Change in the quality of life assessed by COV19-QoL scale Safety of the interventions will be assessed by comparing hematological and biochemical investigations before and after the intervention period and Adverse Event/ Adverse drug reaction TIMELINES FOR OUTCOME ASSESSMENT: Subjective parameters and clinical assessment will be assessed at baseline, 15th day, 30th day, 60th day and 90th day. Laboratory parameters (CBC, LFT, KFT, HbA1c, Hs-CRP, D-dimer), Pulmonary function test and HRCT Chest will be done at baseline and after completion of study period i.e. 90th day. RANDOMISATION: Statistical package for Social Sciences (SPSS) version 15.0 is used to generate the random number sequences. The participants will be randomized to two study groups in the ratio of 1:1. BLINDING (MASKING): The study is open-label design. However, the outcome assessor will be kept blinded regarding the study group allocation of the participants. NUMBERS TO BE RANDOMISED (SAMPLE SIZE) SAMPLE SIZE: The sample size for the study is calculated assuming improvement in 6-minutes walk test by 40 meter in Group I and a change of 10 meter in Group II with a standard deviation of 50 meter based on the results of the previous studies, with 95% Confidence Level (α = 0.05) and 80% power and expecting a dropout rate of 20%. The number of participants to be enrolled in the study should be approximately 55 in each group. Hence, a total of 110 participants will be enrolled in the trial at each study site. TRIAL STATUS: Participants' recruitment started on 1st May 2021. Anticipated end of recruitment is August 2021. Protocol number: CCRAS-01 Protocol version number: 1.1, 13th January 2021. TRIAL REGISTRATION: The trial is prospectively registered with the Clinical Trial Registry of India (CTRI) on 03rd March 2021 [ CTRI/2021/03/031686 ]. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Journal website (Additional file 1). This communication serves as a summary of the key elements of the full protocol.

Comparative retrospective open-label study of ayurvedic medicines and their combination with allopathic drugs on asymptomatic and mildly-symptomatic COVID-19 patients.

INTRODUCTION: Treatment for COVID-19 was ambiguous in the beginning of the pandemic. At that time, the conventional medical system was grappling to cope with the rapidly spreading pandemic. The potential of Ayurveda, one of the branches of traditional Indian medicine (TIM), with a 5000 year old history, employing medicines derived from plants and other natural sources, against COVID-19 has been explored through a comparative retrospective open-label study. METHODS: Reported here are the remedial effects of Ayurvedic medicines alone or in combination with Allopathic treatment on 59 asymptomatic or mildly symptomatic COVID-19 patients, across multiple COVID-19 care centers in Ahmedabad, India. The patients were confirmed for COVID-19 infection through RT-qPCR of nasopharyngeal swabs. With informed consents from the patients, the sourced data was divided into 'Allopathic and Ayurvedic' [AlloAyur] (n = 41) and 'Ayurvedic only'[Ayur] (n = 18) groups, based on the type of treatment the patients decided to receive, that is Ayurvedic medicines with Allopathic treatment or Ayurvedic medicines alone, respectively. Ayurvedic medicines included oral doses and nasal drops; the dosage and regime were decided based on the recommendations from Ayurvedic texts. The Allopathic medicines included Azithromycin, Vitamin-C and anti-histamines. Acetaminophen was also administered when necessary, by the attending physician. The patients were observed for symptomatic improvement. RESULTS: Primary outcome of this study was the symptomatic relief from COVID-19. Data collected over a period of two months, showed that more patients exhibited symptomatic relief in Ayur goup (83.33 %) than in the AlloAyur group (48.78 %) within the first 13 days of treatment. No visible adverse effects were observed. This indicated faster and safe symptomatic resolution among those treated with Ayurvedic medicines alone. CONCLUSION: Patients receiving only Ayurvedic medicines on average were symptomatically relieved faster than those receiving Allopathic and Ayurvedic medicines together.

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

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.

COVID19-inhibitory activity of withanolides involves targeting of the host cell surface receptor ACE2: insights from computational and biochemical assays.

SARS-CoV-2 outbreak in China in December 2019 and its spread as worldwide pandemic has been a major global health crisis. Extremely high infection and mortality rate has severely affected all sectors of life and derailed the global economy. While drug and vaccine development have been prioritized and have made significant progression, use of phytochemicals and herbal constituents is deemed as a low-cost, safer and readily available alternative. We investigated therapeutic efficacy of eight withanolides (derived from Ashwagandha) against the angiotensin-converting enzyme 2 (ACE2) proteins, a target cell surface receptor for SARS-CoV-2 and report results on the (i) computational analyses including binding affinity and stable interactions with ACE2, occupancy of ACE2 residues in making polar and nonpolar interactions with different withanolides/ligands and (2) in vitro mRNA and protein analyses using human cancer (A549, MCF7 and HSC3) cells. We found that among all withanolides, Withaferin-A, Withanone, Withanoside-IV and Withanoside-V significantly inhibited the ACE2 expression. Analysis of withanolides-rich aqueous extracts derived from Ashwagandha leaves and stem showed a higher ACE2 inhibitory potency of stem-derived extracts. Taken together, we demonstrated the inhibitory potency of Ashwagandha withanolides and its aqueous extracts against ACE2.Communicated by Ramaswamy H. Sarma.

SARS CoV-2: Progression and treatment protocols - An overview.

COVID-19 pandemic is a global health crisis which has affected citizens of all nations. With more than a million death cases, this outbreak has already had a significant impact on the physical and mental wellbeing of mankind. Considerable amount of research is going on worldwide to find out effective drugs against the virus. Chloroquine phosphate, an antimalarial drug is currently used for the treatment. Studies on the harmful effects of chloroquine is in progress. India is rich in traditional medical practicing such as Ayurveda, Siddha, Unani etc. Ministry of AYUSH is trying to implement an interdisciplinary treatment encompassing all traditional methodologies. It is proven that Ashwagandha rasayana (Withania sominefera L.Dunal) has better functions than hydroxychloroquine. The ayurvedic formulations such as Sudarshan Ghanvati and Sanshamanivati are also used. The combination of hydroxychloroquine (HCQ) and azithromycin is found to cure COVID-19 more effectively. Use of Tocilizumab is found to cure the respiratory disorders associated with COVID. Favilavir turns out to be yet another effective drug. The alternative medical system has effective prophylaxis and is considered better for the treatment of COVID-19. Ayurveda and yoga improve immunity thus maintaining good health. This review throws light on the mode of progression of the virus along with the various treatment protocols adopted to fight COVID-19.

Withaferin A: a potential therapeutic agent against COVID-19 infection.

The outbreak and continued spread of the novel coronavirus disease 2019 (COVID-19) is a preeminent global health threat that has resulted in the infection of over 11.5 million people worldwide. In addition, the pandemic has claimed the lives of over 530,000 people worldwide. Age and the presence of underlying comorbid conditions have been found to be key determinants of patient mortality. One such comorbidity is the presence of an oncological malignancy, with cancer patients exhibiting an approximate two-fold increase in mortality rate. Due to a lack of data, no consensus has been reached about the best practices for the diagnosis and treatment of cancer patients. Interestingly, two independent research groups have discovered that Withaferin A (WFA), a steroidal lactone with anti-inflammatory and anti-tumorigenic properties, may bind to the viral spike (S-) protein of SARS-CoV-2. Further, preliminary data from our research group has demonstrated that WFA does not alter expression of ACE2 in the lungs of tumor-bearing female mice. Downregulation of ACE2 has recently been demonstrated to increase the severity of COVID-19. Therefore, WFA demonstrates real potential as a therapeutic agent to treat or prevent the spread of COVID-19 due to the reported interference in viral S-protein to host receptor binding and its lack of effect on ACE2 expression in the lungs.