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1.
J Herb Med ; 29: 100472, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1240374

ABSTRACT

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.

2.
Drug Des Devel Ther ; 15: 1111-1133, 2021.
Article in English | MEDLINE | ID: covidwho-1150609

ABSTRACT

Purpose: SARS-CoV-2 engages human ACE2 through its spike (S) protein receptor binding domain (RBD) to enter the host cell. Recent computational studies have reported that withanone and withaferin A, phytochemicals found in Withania somnifera, target viral main protease (MPro) and host transmembrane TMPRSS2, and glucose related protein 78 (GRP78), respectively, implicating their potential as viral entry inhibitors. Absence of specific treatment against SARS-CoV-2 infection has encouraged exploration of phytochemicals as potential antivirals. Aim: This study aimed at in silico exploration, along with in vitro and in vivo validation of antiviral efficacy of the phytochemical withanone. Methods: Through molecular docking, molecular dynamic (MD) simulation and electrostatic energy calculation the plausible biochemical interactions between withanone and the ACE2-RBD complex were investigated. These in silico observations were biochemically validated by ELISA-based assays. Withanone-enriched extract from W. somnifera was tested for its ability to ameliorate clinically relevant pathological features, modelled in humanized zebrafish through SARS-CoV-2 recombinant spike (S) protein induction. Results: Withanone bound efficiently at the interacting interface of the ACE2-RBD complex and destabilized it energetically. The electrostatic component of binding free energies of the complex was significantly decreased. The two intrachain salt bridge interactions (K31-E35) and the interchain long-range ion-pair (K31-E484), at the ACE2-RBD interface were completely abolished by withanone, in the 50 ns simulation. In vitro binding assay experimentally validated that withanone efficiently inhibited (IC50=0.33 ng/mL) the interaction between ACE2 and RBD, in a dose-dependent manner. A withanone-enriched extract, without any co-extracted withaferin A, was prepared from W. somnifera leaves. This enriched extract was found to be efficient in ameliorating human-like pathological responses induced in humanized zebrafish by SARS-CoV-2 recombinant spike (S) protein. Conclusion: In conclusion, this study provided experimental validation for computational insight into the potential of withanone as a potent inhibitor of SARS-CoV-2 coronavirus entry into the host cells.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Antiviral Agents/pharmacology , COVID-19/drug therapy , SARS-CoV-2/drug effects , Spike Glycoprotein, Coronavirus/metabolism , Withania , Withanolides/pharmacology , A549 Cells , Animals , Antiviral Agents/chemistry , Antiviral Agents/isolation & purification , COVID-19/enzymology , COVID-19/virology , Disease Models, Animal , Female , Host-Pathogen Interactions , Humans , Male , Molecular Docking Simulation , Molecular Dynamics Simulation , Protein Interaction Domains and Motifs , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/chemistry , Static Electricity , Structure-Activity Relationship , Virus Internalization/drug effects , Withania/chemistry , Withanolides/chemistry , Withanolides/isolation & purification , Zebrafish
3.
J Inflamm Res ; 14: 869-884, 2021.
Article in English | MEDLINE | ID: covidwho-1138640

ABSTRACT

Purpose: Coronil is a tri-herbal formulation containing extracts from Withania somnifera, Tinospora cordifolia, and Ocimum sanctum. Recently, it was shown that Coronil rescued humanized zebrafish from SARS-CoV-2 induced pathologies. Based on reported computational studies on the phytochemicals present in Coronil, it could be a potential inhibitor of SARS-CoV-2 entry into the host cell and associated cytokines' production. Methods: Through an ELISA-based biochemical assay, effects of Coronil on interaction between ACE-2 and different mutants of viral spike (S) protein, crucial for viral invasion of host cell, were evaluated. Additionally, using recombinant pseudoviruses having SARS-CoV-2 spike (S) protein in their envelopes and firefly luciferase reporter in their genomes, effects of Coronil on virus entry into human alveolar epithelial cells were evaluated through luciferase assay. UHPLC profiled Coronil also modulated S-protein mediated production of pro-inflammatory cytokines in A549 cells, like interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α), as evaluated through RT-qPCR and ELISA. Results: Coronil effectively inhibited the interaction of ACE-2 not only with the wild-type S protein (SWT) but also with its currently prevalent and more infectious variant (SD614G) and another mutant (SW436R) with significantly higher affinity toward ACE-2. Treatment with Coronil significantly reduced the increased levels of IL-6, IL-1ß, and TNF-α in A549 cells incubated with different S-protein variants in a dose-dependent manner. Likewise, it also prevented the SARS-CoV-2 S-protein pseudotyped vesicular stomatitis virus (VSVppSARS-2S) mediated cytokine response in these cells by reducing entry of pseudoviruses into host cells. Conclusion: Coronil prevented SARS-CoV-2 S-protein mediated viral entry into A549 cells by inhibiting spike protein-ACE-2 interactions. SARS-CoV-2 S protein induced inflammatory cytokine response in these cells was also moderated by Coronil.

4.
Phytomedicine ; 84: 153494, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1062560

ABSTRACT

BACKGROUND: Specific treatment for COVID-19 is still an unmet need. Outcomes of clinical trials on repurposed drugs have not been yielding success. Therefore, it is necessary to include complementary approaches of medicine against COVID-19. PURPOSE: This study was designed to evaluate the impact of traditional Indian Ayurvedic treatment regime on asymptomatic patients with COVID-19 infection. STUDY DESIGN: It is a placebo controlled randomized double-blind pilot clinical trial. METHODS: The study was registered with Clinical Trial Registry-India (vide Registration No. CTRI/2020/05/025273) and conducted at the Department of Medicine in National Institute of Medical Sciences and Research, Jaipur, India. 1 g of Giloy Ghanvati (Tinospora cordifolia) and 2 g of Swasari Ras (traditional herbo-mineral formulation) and 0.5 g each of Ashwagandha (Withania somnifera) and Tulsi Ghanvati (Ocimum sanctum) were given orally to the patients in treatment group twice per day for 7 days. Medicines were given in the form of tablets and each tablet weighed 500 mg. While, Swasari Ras was administered in powdered form, 30 min before breakfasts and dinners, rest were scheduled for 30 min post-meals. Patients in the treatment group also received 4 drops of Anu taila (traditional nasal drop) in each nostril every day 1 h before breakfast. Patients in the placebo group received identical-looking tablets and drops, post randomization and double blinded assortments. RT-qPCR test was used for the detection of viral load in the nasopharyngeal and oropharyngeal swab samples of study participants during the study. Chemiluminescent immunometric assay was used to quantify serum levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) and high sensitivity C-reactive protein (hs-CRP) on day 1 and day 7 of the study. RESULTS: By day 3, 71.1 % and 50.0 % patients recovered in the treatment and placebo groups, respectively. Treatment group witnessed 100 % recovery by day 7, while it was 60.0 % in the placebo group. Average fold changes in serum levels of hs-CRP, IL-6 and TNF-α in treatment group were respectively, 12.4, 2.5 and 20 times lesser than those in the placebo group at day 7. There was 40 % absolute reduction in the risk of delayed recovery from infection in the treatment group. CONCLUSIONS: Ayurvedic treatment can expedite virological clearance, help in faster recovery and concomitantly reduce the risk of viral dissemination. Reduced inflammation markers suggested less severity of SARS-CoV-2 infection in the treatment group. Moreover, there was no adverse effect observed to be associated with this treatment.


Subject(s)
COVID-19/drug therapy , Medicine, Ayurvedic , Plant Preparations/therapeutic use , Adolescent , Adult , Double-Blind Method , Female , Hospitalization , Humans , India , Male , Middle Aged , Pilot Projects , Treatment Outcome , Young Adult
5.
AMB Express ; 10(1): 210, 2020 Dec 01.
Article in English | MEDLINE | ID: covidwho-951800

ABSTRACT

COVID-19 pandemic has almost made hand sanitization a ritual resulting in a steep increase in the frequency of hand sanitization and an unprecedented surge in demand for hand sanitizers. In fact, several governments had to ration hand sanitizers in the retail outlets and over the counter chemist shops. Additionally, Indian government has put a cap on the prices of hand sanitizers. Currently, large sections of global and Indian population are grappling under financial crises. Therefore, mandatory hand sanitization has made an unwelcoming, yet unavoidable addition to the already-hard-to-maintain-grocery-list. Here, we have compared the anti-microbial efficacy of Patanjali Hand Sanitizer (PHS), developed and marketed by Patanjali Ayurved Ltd. (an India-based food and herbal medicine company) with one of the topmost hand sanitizers currently used under clinical set-ups. PHS has anti-microbial efficacy comparable to that of the standard hand sanitizer. Besides, disc diffusion and time-dependent thumb print assays showed that PHS has longer retentivity on the applied surfaces, suggesting lesser consumption of the sanitizer and concomitant relaxation on the monthly grocery budget. Observed anti-bacterial potency of PHS is attributed to the disruption of bacterial cell membrane, as employed by alcohol-based hand sanitizers. A rough estimation revealed that PHS is ~ 4.3 times cost effective than the standard hand sanitizer used as the positive control in this study. Taken together, PHS is a suitable alternative for existing hand sanitizers available in the market that can relax the demand-supply strain and soften significantly the burden of monthly expenditure on hand sanitizers.

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