Evaluating therapeutic potential of AYUSH-64 constituents against omicron variant of SARS-CoV-2 using ensemble docking and simulations.

The COVID-19 pandemic in the later phase showed the presence of the B.1.1.529 variant of the SARS-CoV-2 designated as Omicron. AYUSH-64 a poly herbal drug developed by Central Council for Research in Ayurvedic Sciences (CCRAS) has been recommended by Ministry of Ayush in asymptomatic, mild to moderate COVID-19 patients. One of the earlier, in-silico study has shown the binding of the constituents of AYUSH-64 to the main protease (Mpro) of the SARS-CoV-2. This study enlisted four phytochemicals of AYUSH-64, which were found to have significant binding with the Mpro. In continuation to the same, the current study proposes to understand the binding of these four phytochemicals to main protease (Mpro) and receptor binding domain (RBD) of spike protein of the Omicron variant. An enhanced molecular docking methodology, namely, ensemble docking has been used to find the most efficiently binding phytochemical. Using molecular dynamics (MD) simulations and clustering approach it was observed that the Mpro and RBD Spike of Omicron variant of SARS-CoV-2 in complex with human ACE2 tends to attain 4 and 8 conformational respectively. Based on the docking studies, the best binding phytochemical of the AYUSH-64, akummicine N-oxide was selected for MD simulations. MD simulations of akummicine N-oxide bound to omicron variant of Mpro and RBD Spike-ACE complex was performed. The conformational, interaction and binding energy analysis suggested that the akummicine N-oxide binds well with Mpro and RBD Spike-ACE2 complex. The interaction between RBD Spike and ACE2 was observed to weaken in the presence of akummicine N-oxide. Hence, it can be inferred that, these phytochemicals from AYUSH-64 formulation may have the potential to act against the Omicron variant of SARS-CoV-2.

Co-administration of AYUSH 64 as an adjunct to standard of care in mild and moderate COVID-19: A randomized, controlled, multicentric clinical trial.

OBJECTIVE: Evaluate the efficacy of AYUSH 64, a standard polyherbal Ayurvedic drug in COVID-19. METHODS: During the first pandemic wave, 140 consenting and eligible hospitalized adult participants with mild-moderate symptomatic disease (specific standard RT-PCR assay positive) were selected as per a convenience sample, and randomized (1:1 ratio) to an open-label (assessor blind) two-arm multicentric drug trial; standard of care (SOC as per Indian guidelines) versus AYUSH 64 combined with SOC (AYUSH plus). Participants were assessed daily and discharged once clinical recovery (CR, primary efficacy) was achieved which was based on a predetermined set of criteria (resolution of symptoms, normal peripheral oximetry, and negative specific RT-PCR assay). Each participant was followed using an indigenous software program(mobile phone) and completed a 12-week study period. The dose of AYUSH 64 was 2 tablets oral, 500 mg each, bid for 12 weeks (AYUSH plus only). Significant P was <0.05 (two-sided). On randomization, the groups were found well matched. RESULTS: The mean interval time from randomization to CR was significantly superior in the AYUSH plus group [mean 6.45 days versus 8.26 days, 95% Confidence Interval of the difference -3.02 to -0.59 (P = 0.003, Student's 't test] as per-protocol analysis (134 participants); significant (P = 0.002) on an intention to treat analysis. 70% of the participants in AYUSH plus recovered during the first week (P = 0.046, Chi-square) and showed a significantly better change in physical health, fatigue, and quality of life measures. 48 adverse events, mostly mild and gut related, were reported by each group. There were 20 patient withdrawals (8 in AYUSH plus) but none due to an AE. There were no deaths. Daily assessment (hospitalization) and supervised drug intake ensured robust efficacy data. The open-label design was a concern (study outcome). CONCLUSIONS: AYUSH 64 in combination with SOC hastened recovery, reduced hospitalization, and improved health in COVID-19. It was considered safe and well-tolerated. Further clinical validation (Phase III) is required. TRIAL REGISTRATION: CTRI/2020/06/025557.

Efficacy and safety of Ayurveda interventions for sinusitis: a systematic review and meta-analysis.

OBJECTIVES: To provide a broad evaluation of the efficacy and safety of Ayurveda interventions for the management of sinusitis. METHODS: Five electronic databases for published research articles, three databases for the dissertation/doctoral thesis works, clinical trial registries, and hand searches were done till May 2021. All comparative clinical trials recruiting sinusitis patients of any age group, receiving Ayurveda intervention, regardless of forms, dosages, and ingredients, for not less than one week were included. The data extraction and the risk of bias (RoB) assessment were done by two reviewers independently. RESULTS: A total of 2,824 records were identified, of which 09 randomized parallel arms trials met inclusion criteria. No studies were found comparing Ayurveda vs. placebo or non-Ayurveda interventions. Combined Ayurveda therapy (CT) was statistically more beneficial compared with either procedural or non-procedural Ayurveda therapy alone in reducing symptoms nasal discharge (standardized MD -0.71, 95% CI -1.16 to -0.26, I 2 58%, 210 participants) and headache (standardized MD -0.44, 95% CI -0.86 to -0.02, I 2 56%, 218 participants), however, no significant difference was found in reducing symptoms nasal obstruction and loss of smell. No data related to the safety of Ayurveda intervention was found. All the trials (09) were having 'high' to 'some concern' overall bias. CONCLUSIONS: Although individual studies appeared to produce positive results, very low certainty of total effect hindered to arrive at any conclusion regarding efficacy or safety of Ayurveda interventions for sinusitis. There is a need for well-designed-executed-reported clinical studies on clinically relevant outcomes. TRIAL REGISTRATION MUMBER: CRD42018103995.

Learnings from a veteran oncologist's long-standing efforts in integrative oncology.

Kerala's first medical oncologist, the erstwhile Dr. CP Mathew, has left a rich legacy in cancer patients' case diaries and medical records. These documents contain valuable information about his attempts to integrate Siddha and Ayurveda treatments to manage cancer. A preliminary examination of these documents compiled over more than four decades gives us a glimpse of his contributions relevant to the development of Integrative Oncology in India. Patients who received treatment from Dr. CP Mathew presented with different types of cancer in varying stages of progression. In his clinical practice, he developed treatment approaches that integrated Ayurveda and Siddha with the standard of care for specific types and presentations of cancer. At Cherian Ashram in Kottayam, where he treated cancer patients, a team of medical doctors, including a senior Ayurveda physician and a Naturopathy and Yoga expert, worked together to offer integrative care. Based on his experience, he emphasized that the public should be made aware of the available options for alternative treatments even in advanced stages of cancer. While Ayurveda and Siddha could bolster the patient's immunity and improve clinical outcomes, he pointed out that such interventions could also improve tolerance to chemotherapy and radiation. In the wake of the growing global interest in Integrative Oncology, the work of Dr. CP Mathew preserved in the medical records of his cancer patients deserves to be studied with an open mind.

AYUSH 64, a polyherbal Ayurvedic formulation in Influenza-like illness - Results of a pilot study.

BACKGROUND: Influenza-like Illness (ILI) refers to a wide range of viral infections with an important cause of morbidity and mortality worldwide. The global incidence of ILI is estimated at 5-10% in adults and 20-30% in children. In India influenza accounts for 20-42% of monthly acute medical illness hospitalizations during the peak rainy season. AYUSH-64, a poly-herbal drug, is in practice for 40 years for various clinical conditions like fevers, microfilaremia, and inflammatory conditions. OBJECTIVE: A pilot study was conducted to evaluate the safety and efficacy of Ayurvedic formulation, AYUSH-64 in clinically diagnosed ILI for accelerating the recovery. MATERIAL AND METHODS: A prospective, open-label, nonrandomized, single group, single-center pilot clinical study with pre-test and post-test design was conducted at Raja Ramdeo Anandilal Podar Central Ayurveda Research Institute for Cancer, Mumbai, an institute of Central Council for Research in Ayurvedic Sciences (CCRAS) between June 2018 and July 2019. A total of 38 participants of clinically diagnosed ILI (18-65 years) were studied with an one-week intervention of 'AYUSH 64' in a dose of 3 gm/day and three weeks post-treatment observation period. Assessment of parameters viz. improvement in the symptoms of ILI, frequency of usage of acetaminophen, antihistaminic and cough syrup, hematology, liver function and kidney function tests along with incidence of secondary complications, and time to return to a normal routine was done. RESULTS: One-week intervention of AYUSH 64 helped to recover from ILI symptoms with reduced frequency of usage of acetaminophen and antihistaminic. The intervention was safe on hematology and biochemical parameters. No serious adverse effects were observed during the study. CONCLUSION: AYUSH 64 along-with standard care in ILI is safe and efficacious and this may be used in other viral infections with pyrexia as add-on to standard care for early recovery and better outcome.

In silico evaluation of the compounds of the ayurvedic drug, AYUSH-64, for the action against the SARS-CoV-2 main protease.

BACKGROUND: Outbreak of Corona Virus Disease in late 2019 (COVID-19) has become a pandemic global Public health emergency. Since there is no approved anti-viral drug or vaccine declared for the disease and investigating existing drugs against the COVID-19. OBJECTIVE: AYUSH-64 is an Ayurvedic formulation, developed and patented by Central Council of Research in Ayurvedic Sciences, India, has been in clinical use as anti-malarial, anti-inflammatory, anti-pyretic drug for few decades. Thus, the present study was undertaken to evaluate AYUSH-64 compounds available in this drug against Severe Acute Respiratory Syndrome-Corona Virus (SARS-CoV-2) Main Protease (Mpro; PDB ID: 6LU7) via in silico techniques. MATERIALS AND METHODS: Different molecular docking software's of Discovery studio and Auto Dock Vina were used for drugs from selected AYUSH-64 compounds against SARS-CoV-2. We also conducted 100 ns period of molecular dynamics simulations with Desmond and further MM/GBSA for the best complex of AYUSH-64 with Mpro of SARS-CoV-2. RESULTS: Among 36 compounds of four ingredients of AYUSH-64 screened, 35 observed to exhibits good binding energies than the published positive co-crystal compound of N3 pepetide. The best affinity and interactions of Akuammicine N-Oxide (from Alstonia scholaris) towards the Mpro with binding energy (AutoDock Vina) of -8.4 kcal/mol and Discovery studio of Libdock score of 147.92 kcal/mol. Further, molecular dynamics simulations with MM-GBSA were also performed for Mpro- Akuammicine N-Oxide docked complex to identify the stability, specific interaction between the enzyme and the ligand. Akuammicine N-Oxide is strongly formed h-bonds with crucial Mpro residues, Cys145, and His164. CONCLUSION: The results provide lead that, the presence of Mpro- Akuammicine N-Oxide with highest Mpro binding energy along with other 34 chemical compounds having similar activity as part of AYUSH-64 make it a suitable candidate for repurposing to management of COVID-19 by further validating through experimental, clinical studies.

Subcutaneous intralesional Ksharodaka injection: A novel treatment for the management of Warts: A case series.

Warts are generally managed using cryosurgery, keratolytic ointments, curettage and electrodessication. Warts, vis-a-vis Charmakila, in Ayurvedic classical texts are classified into different types depending on the dominance of dosha. Ayurveda prescribes oral medications, topical use of Kshara (alkaline ash of herbs), Agni (thermal cautery) and Shastrakarma (surgery) for removal of Charmakila. Use of topical Kshara in the form of powder, aqueous solution i.e. Ksharodaka and Ksharasutra (thread smeared with Kshara) for warts has been reported. However, these methods necessitate multiple sittings and takea longer duration for removal of the warts. Herewith, we report a case series of different types of warts treated with intralesional infiltration of Apamarga Ksharodaka (AK), i.e. aqueous solution of Apamarga (Achyranthes aspera) Kshara. We observed that all these warts took a minimum of 2-6 days to shed off, leaving minor scars. There were no adverse reactions reported in any of these cases.

Basti: Does the equipment and method of administration matter?

Basti is one of the five procedures of panchakarma in Ayurveda. Classically, it is advocated in the diseases of vata. It is mainly of two types viz. asthapana and anuvasana. According to the classical texts basti administration is done with the help of animal bladder (bastiputaka) and specially prepared metal/wooden nozzle/catheter (bastinetra), the whole assembly is called as bastiyantra. Nowadays, except in some of the Vaidya traditions in Kerala, basti administration is often done using enema-can or douche-set. In the aforesaid classical procedure active pressure is expected to be given on the bastiputaka whereas, in conventionally used enema-can only passive or gravitational force plays a role. This is important in the context of 'basti danakala or pidanakala i.e. time for basti administration'.