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

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections generate approximately one million virions per day, and the majority of available antivirals are ineffective against it due to the virus's 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 coronavirus disease (COVID-19) by targeting multiple key viral target proteins. Fortunellin supports 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 an antiviral activity that is 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. We have used molecular docking, molecular dynamics simulations, free-energy calculations, host target mining of fortunellin, gene ontology enrichment, pathway analyses, and protein-protein interaction analysis. We discovered that fortunellin reliably binds to key targets that are necessary for viral replication, growth, invasion, and infectivity including Nucleocapsid (N-CTD) (-54.62 kcal/mol), Replicase-monomer at NSP-8 binding site (-34.48 kcal/mol), Replicase-dimer interface (-31.29 kcal/mol), Helicase (-30.02 kcal/mol), Papain-like-protease (-28.12 kcal/mol), 2'-O-methyltransferase (-23.17 kcal/mol), Main-protease (-21.63 kcal/mol), Replicase-monomer at dimer interface (-22.04 kcal/mol), RNA-dependent-RNA-polymerase (-19.98 kcal/mol), Nucleocapsid-NTD (-16.92 kcal/mol), and Endoribonuclease (-16.81 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 (NHBE) and lung cells and organoids such as pancreatic, colon, liver, and cornea using a network pharmacology approach. Thus, our findings indicate that fortunellin has a dual role; multi-target antiviral activities against SARS-CoV-2 and immunomodulatory capabilities against the host.

Clinical assessment of dietary interventions and lifestyle modifications in Madhumeha (type- 2 Diabetes Mellitus).

BACKGROUND: India leads the world with maximum number of diabetes patients being termed as the "diabetes capital of the world." Certain risk factors including unsatisfactory diet, overweight, and a sedentary lifestyle are potentially reversible. Acharayas have widely described the role of diet and activities to control Madhumeha (type 2 diabetes mellitus [T2DM]) along with medications. Habitual consumption of roasted or dry Barley (Hordeum vulgare L.) flour, Mudga (Phaseolus aureus Roxb.) and Amalaki (Emblica officinalis Gaertn.) prevents the manifestation of Prameha. AIM: To assess the clinical effects of dietary interventions and life style modifications in Madhumeha patients. MATERIALS AND METHODS: Present study was carried out on 56 patients of Madhumeha from S.S. Hospital, Banaras Hindu University, Varanasi. Dietary interventions and life style modifications schedule was prepared based on Ayurvedic principles and patients were advised to follow this regimen. Three consecutive follow-ups were done for 3 months at the interval of one month each. RESULTS: Significant improvement was observed in clinical signs and symptoms along with plasma glucose and glycosylated hemoglobin (HbA1c) in Madhumeha patients after these interventions (P < 0.001). CONCLUSION: Dietary interventions and life style modifications are two important tools by which adequate glycemic control can be obtained, especially in newly diagnosed T2DM patients and in patients who are on antidiabetic medication, but not properly controlled.

Impact of season and constitution on lipid parameters.

Ayurveda prescribes daily and seasonal regimen in maintaining good health. Measures in the preservation of health have been described considering one's own Prakriti, Satva, Vayas, Bala, Agni, Ojus, season, and so on. Depending on the relative predominance of Doshas in various constitutions and seasons, certain regimens have been prescribed. The present study was done to assess the lipid profile in 54 healthy volunteers. It was observed from the present data that winter month is one of the potential risk factors for cardiovascular diseases because more lipid profile level was observed during winter. Among the constitutions, Kapha and Pitta Prakriti are more vulnerable for cardiovascular diseases because more lipid profile level is observed in these constitutions during winter.

Critical appraisal of Doshavaha Srotas.

Tridoshas viz Vata, Pitta, and Kapha are responsible for health and disease depending on their normalcy and disequilibrium state. Improper usage of foods and drinks along with abnormal activities manifests diseases of respective Doshik predominance. Sira (vein) is the synonym of Srotas, keeping this in mind, Vatavaha Sira is correlated with Vatavaha Srotas, Pittavaha Sira with Pittavaha Srotas, Kaphavaha Sira with Kaphavaha Srotas, and Sarvavaha Sira with Sarvavaha Srotas. The purpose of detail understanding of Doshavaha Srotas is essential to understand the role of Doshas in the manifestation of diseases. One can easily predict by observing the color changes in particular area to be able to predict the predominance of Doshas in that area. Manifestation of a disease occurs in the body as a result of the defective Srotas favoring the Dosha-Dushya conglomeration. Hence, any defect in the Srotas must be corrected quickly for the restoration of normal health. Present article emphasis on the proper understanding of Doshavaha Srotas in a systematic manner to understand its root, causative factors, signs and symptoms, and diseases produced due to their vitiation.