4 research outputs found

    Computational exploration of the dual role of the phytochemical fortunellin: antiviral activities against SARS-CoV-2 and immunomodulatory abilities against the host

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    SARS-CoV-2 infection generates approximately one million virions per day, and the majority of available antivirals are ineffective against it due to the virus\u27s inherent genetic mutability. This necessitates the investigation of concurrent inhibition of multiple SARS-CoV-2 targets. We show that fortunellin (acacetin 7-O-neohesperidoside), a phytochemical, is a promising candidate for preventing and treating COVID-19 and SARS by targeting multiple key viral target proteins, supporting protective immunity while inhibiting pro-inflammatory cytokines and apoptosis pathways, and protecting against tissue damage. Fortunellin is a phytochemical found in Gojihwadi Kwath, an Indian traditional Ayurvedic formulation with antiviral activity that has been shown to be effective in COVID-19 patients. The mechanistic action of its antiviral activity, however, is unknown. The current study comprehensively evaluates the potential therapeutic mechanisms of fortunellin in preventing and treating COVID-19 using molecular docking, molecular dynamics simulations, free-energy calculations, host target mining of fortunellin, gene ontology enrichment, pathway analyses, and protein-protein interaction analysis. Using computational approaches, we show that fortunellin reliably binds to key targets that are necessary for viral replication, growth, invasion, and infectivity, including Nucleocapsid (N-CTD) (-51.30 kcal/mol) and Replicase-dimer ( -45.91 kcal/mol), Replicase-monomer-NSP-8 binding site (-29.9 kcal/mol), Papain-like-protease (-29.60 kcal/mol), Nucleocapsid-NTD (28.46 kcal/mol), 2’-O-methyltransferase (-24.33 kcal/mol), Main-protease (-23.48 kcal/mol), Spike-RBD (-23.3 kcal/mol), Replicase-monomer at dimer interface (-23.27) kcal/mol, RNA-dependent-RNA-polymerase (-14.24 kcal/mol). Furthermore, we identify and evaluate the potential human targets of fortunellin and its effect on the SARS-CoV-2 infected tissues, including normal-human-bronchial-epithelium and lung cells, and organoids such as pancreatic, colon, liver, and cornea, using a computational network pharmacology approach. Thus, our findings indicate that fortunellin has a dual role: multi-target antiviral activities against SARS-CoV-2, as well as immunomodulatory capabilities against the host. In the future, lab-based and clinical studies will be required

    Clinical efficacy of Gojihvadi Kwath, Shirishadi Kwath, Sanjeevani Vati, Panchagavya Ghrita Granules & Shunthi Churna for COVID-19 management, a randomized controlled trial

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    729-738The obscure disease pattern of COVID -19 have to be evaluated with Ayurvedic interventions and the present clinical trial was a randomized open label parallel three-arm control trial on the major and minor symptomatic patients with the recent pandemic. The patients were recruited from the Super specialty building of Sir Sunderlal hospital, COVID- 19 ward and home isolated ones. The Ayurvedic intervention includes the 15 days oral administration (Group A) –Gojihvadi Kwath, Sanjeevani Vati; Panchagavya Ghrit Granules; Shunthi (Dry ginger powder) plus conventional treatment, in (Group B) –Shirishadi Kwath, Sanjeevani Vati; Panchagavya Ghrit Granules; Shunthi (Dry ginger powder) plus conventional treatment and in Group C (control group) only the conventional medicines. Assessment was done based on the RT-PCR reports, signs and symptoms. The results point out the efficacy of trial medicine (that is group A and B) to discharge the patients earlier than those from the control group. The early reduction in the signs and symptoms noted were also observed. Group B showed a faster recovery from dry cough and shortness of breath and improvement in appetite. Home-isolation patients showed faster recovery of clinical symptoms than the hospitalized patients. Ayurvedic interventions can accelerate viral load clearance associated with quicker recovery and concurrently decrease the risk of viral dissemination. Additionally, there were no adverse reactions observed with these trial medicines

    Clinical efficacy of Gojihvadi Kwath, Shirishadi Kwath, Sanjeevani Vati, Panchagavya Ghrita Granules & Shunthi Churna for COVID-19 management, a randomized controlled trial

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    The obscure disease pattern of COVID -19 have to be evaluated with Ayurvedic interventions and the present clinical trial was a randomized open label parallel three-arm control trial on the major and minor symptomatic patients with the recent pandemic. The patients were recruited from the Super specialty building of Sir Sunderlal hospital, COVID- 19 ward and home isolated ones. The Ayurvedic intervention includes the 15 days oral administration (Group A) –Gojihvadi Kwath, Sanjeevani Vati; Panchagavya Ghrit Granules; Shunthi (Dry ginger powder) plus conventional treatment, in (Group B) –Shirishadi Kwath, Sanjeevani Vati; Panchagavya Ghrit Granules; Shunthi (Dry ginger powder) plus conventional treatment and in Group C (control group) only the conventional medicines. Assessment was done based on the RT-PCR reports, signs and symptoms. The results point out the efficacy of trial medicine (that is group A and B) to discharge the patients earlier than those from the control group. The early reduction in the signs and symptoms noted were also observed. Group B showed a faster recovery from dry cough and shortness of breath and improvement in appetite. Home-isolation patients showed faster recovery of clinical symptoms than the hospitalized patients. Ayurvedic interventions can accelerate viral load clearance associated with quicker recovery and concurrently decrease the risk of viral dissemination. Additionally, there were no adverse reactions observed with these trial medicines
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