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  1. Bandyopadhyay S, Abiodun OA, Ogboo BC, Kola-Mustapha AT, Attah EI, Edemhanria L, et al.
    J Biomol Struct Dyn, 2022;40(22):11467-11483.
    PMID: 34370622 DOI: 10.1080/07391102.2021.1959401
    Medicinal plants as rich sources of bioactive compounds are now being explored for drug development against COVID-19. 19 medicinal plants known to exhibit antiviral and anti-inflammatory effects were manually curated, procuring a library of 521 metabolites; this was virtually screened against NSP9, including some other viral and host targets and were evaluated for polypharmacological indications. Leads were identified via rigorous scoring thresholds and ADMET filtering. MM-GBSA calculation was deployed to select NSP9-Lead complexes and the complexes were evaluated for their stability and protein-ligand communication via MD simulation. We identified 5 phytochemical leads for NSP9, 23 for Furin, 18 for ORF3a, and 19 for IL-6. Ochnaflavone and Licoflavone B, obtained from Lonicera japonica (Japanese Honeysuckle) and Glycyrrhiza glabra (Licorice), respectively, were identified to have the highest potential polypharmacological properties for the aforementioned targets and may act on multiple pathways simultaneously to inhibit viral entry, replication, and disease progression. Additionally, MD simulation supports the robust stability of Ochnaflavone and Licoflavone B against NSP9 at the active sites via hydrophobic interactions, H-bonding, and H-bonding facilitated by water. This study promotes the initiation of further experimental analysis of natural product-based anti-COVID-19 therapeutics.
    Matched MeSH terms: Polypharmacology
  2. Eng-Chong T, Yean-Kee L, Chin-Fei C, Choon-Han H, Sher-Ming W, Li-Ping CT, et al.
    PMID: 23243448 DOI: 10.1155/2012/473637
    Boesenbergia rotunda is a herb from the Boesenbergia genera under the Zingiberaceae family. B. rotunda is widely found in Asian countries where it is commonly used as a food ingredient and in ethnomedicinal preparations. The popularity of its ethnomedicinal usage has drawn the attention of scientists worldwide to further investigate its medicinal properties. Advancement in drug design and discovery research has led to the development of synthetic drugs from B. rotunda metabolites via bioinformatics and medicinal chemistry studies. Furthermore, with the advent of genomics, transcriptomics, proteomics, and metabolomics, new insights on the biosynthetic pathways of B. rotunda metabolites can be elucidated, enabling researchers to predict the potential bioactive compounds responsible for the medicinal properties of the plant. The vast biological activities exhibited by the compounds obtained from B. rotunda warrant further investigation through studies such as drug discovery, polypharmacology, and drug delivery using nanotechnology.
    Matched MeSH terms: Polypharmacology
  3. Fahrni ML, Azmy MT, Usir E, Aziz NA, Hassan Y
    PLoS One, 2019;14(7):e0219898.
    PMID: 31348784 DOI: 10.1371/journal.pone.0219898
    OBJECTIVES: To provide baseline information on inappropriate prescribing (IP), and to evaluate whether potentially inappropriate medications (PIMs), as defined by STOPP (Screening Tool of Older Persons' potentially inappropriate Prescriptions) criteria, were associated with preventable adverse drug events (ADEs) and/or hospitalization.

    METHODS: We prospectively studied older patients (n = 301) admitted to three urban, public-funded hospitals. We scrutinized their medical records and used STOPP-START (Screening Tool to Alert Prescribers to Right Treatment) criteria to determine PIM and potential prescribing omissions (PPO) respectively- together these constitute IP. Prescriptions with PIM(s) were subjected to a pharmacist medication review, aimed at detecting cases of ADE(s). The vetted cases were further assessed by an expert consensus panel to ascertain: i) causality between the ADE and hospitalization, using, the World Health Organization Uppsala Monitoring Centre criteria, and, ii) whether the ADEs were avoidable (using Hallas criteria). Finally, percentages of PIM-associated ADEs that were both preventable and linked to hospitalization were calculated.

    RESULTS: IP prevalence was 58.5% (n = 176). A majority (49.5%, n = 150) had moderate to severe degree of comorbidities (Charlson Comorbidity Index score ≥ 3). Median age was 72 years. Median number of medications was 6 and 30.9% (n = 93) had ≥8 medications. PIM prevalence was 34.9% (117 PIMs, n = 105) and PPO 37.9% (191 PPOs, n = 114). Most PIMs and PPOs involved overuse of aspirin and underuse of both antiplatelets and statins respectively. With every increase in the number of medications prescribed, the likelihood of PIM occurrence increased by 20%, i.e.1.2 fold (OR 1.20, 95% CI: 1.1-1.3). Among the 105 patients with PIMs, 33 ADEs (n = 33); 31 ADEs (n = 31) considered "causal" or "contributory" to hospitalization; 27 ADEs (n = 27) deemed "avoidable" or "potentially avoidable"; and 25 PIM-associated ADEs, preventable, and that induced hospitalization (n = 25), were identified: these equated to prevalence of 31.4%, 29.5%, 25.7%, and 23.8% respectively. The most common ADEs were masked hypoglycemia and gastrointestinal bleed. With every additional PIM prescribed, the odds for ADE occurrence increased by 12 folds (OR 11.8, 95% CI 5.20-25.3).

    CONCLUSION: The majority of the older patients who were admitted to secondary care for acute illnesses were potentially exposed to IP. Approximately a quarter of the patients were prescribed with PIMs, which were plausibly linked with preventable ADEs that directly caused or contributed to hospitalization.

    Matched MeSH terms: Polypharmacology
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