Browsing by Author "Osiebe, Oghenesivwe"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    BIOASSAY-GUIDED ISOLATION OF FURIN INHIBITORS FROM LEAF EXTRACT OF Momordica charantia L.
    (2022-09-18) Famutimi, Oladoyin Grace; Adewale, Isaac Olusanjo; Osiebe, Oghenesivwe; Aderogba, Mutalib Adeniran
    Proprotein convertase-furin is involved in numerous physiological and pathogenic processes, such as viral propagation, bacterial toxin activation, cancer, and metastasis. Because of its involvement in these disease-related processes, the inhibition of this enzyme could be a promising drug target. The several existing synthetic inhibitors of furin are associated with side effects. Hence, we focused on natural sources, in particular, medicinal plant with antiviral capabilities. This study was designed to isolate the bioactive secondary metabolites present in Momordica charantia leaf extract and determine their potential bioactivity on furin. M. charantia leaves were air-dried, ground to fine powder and extracted using 80% (v/v) methanol. The methanolic extract was concentrated in vacuo at 40 oC and the crude extract obtained was partitioned successively with n-hexane (HEX), dichloromethane (DCM), ethyl acetate (EtOAc) and n-butanol (BuOH). A bioassay-guided screening of the crude extract and solvent fractions was carried out against the activity of recombinant human furin with the release of fluorescent 7-amino-4-methyl coumarin (AMC) liberated from the substrate, Pyroglutamic acid-Arg-Thr-Lys-Arg-methyl-coumaryl-7-amide, in a fluorimeter plate reader. Thereafter, the most potent fraction was subjected to chromatographic separation using thin layer (TLC) and column chromatographic techniques. The eluted fractions and subfractions were screened for bioactivity. The crude extract showed inhibition percentages of 51.9 and 100% at 7 and 12.5 ng/μl, respectively. The HEX fraction (7 ng/μl) exerted the highest inhibition (72%) on furin compared to other fractions while the BuOH fraction activated the enzyme by 1.5%. The chromatographed HEX fraction yielded seven (7) fractions with different physical properties. Five of these fractions gave single spot on TLC plate. Six fractions (MC I to VI) exhibited potent inhibition against furin with inhibition percentages ranging from 67 to 100% when 0.5 ng/μl of the inhibitor was used. Further fractionation of MC VI on preparative thin layer chromatography gave two sub fractions (A and B) which gave 50% inhibition, respectively. Overall, the presence of these potent inhibitors of furin in the leaf extract of M. charantia could provide a rationale for the ethnomedicinal use of the plant for viral infection in Nigerian folk medicine. Also, further investigations are underway for a better understanding and structural elucidation of the secondary metabolites responsible for the bioactivity observed on furin.
  • Thumbnail Image
    Item
    Plant-Derived Compounds with Therapeutic Potential for the Treatment of Human Coronavirus Diseases
    (2024-06-20) Adewale, Isaac Olusanjo; Famutimi, Oladoyin Grace; Osiebe, Oghenesivwe
    Since the advent of modern civilization, few diseases have caused more worldwide socioeconomic disruptions than COVID-19 caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In some countries, very high proportion of the population have contracted the disease even though it is fatal in only a small percentage of those carrying the virus. In addition to physical measures (social distancing, handwashing, sterilization, etc.), two mainpharmaceutical interventions have been adopted: the development of vaccine/mass vaccination and therapeutic intervention. The recent discovery of SARS-CoV-2 transmission among vaccinated individuals and changes in the genome of the virus arising from mutation leading to new variants (delta, omicron, IHU etc.) suggest the importance of therapeutic intervention targeting different aspects of the molecular mechanisms involved in its virulence. Therapeutic agents targeting essential elements required for viral propagation in the host may also nd application in the management of other viral diseases such as Ebola, Zika, and HIV/AIDS. Targets for drug design include the 16 non-structural proteins, RNA-dependent DNA polymerase, esterase, membrane proteins, spike and envelope proteins, protease and nucleocapsid proteins, and helicase, all present on the virus; host proteases and receptors. Both medicinal plant-derived and synthetic compounds including monoclonal antibodies are now suggested as candidate drugs for COVID-19 and are being developed as suitable therapeutic agents. In this review, some useful information on promising plant-derived therapeutic agents are provided which may be of value in the development of drugs for COVID-19 and other viral diseases. 6/26/24, 6:14 PM Plant-Derived Compounds with Therapeutic Potential for the Treatment of Human Coronavirus Diseases | Proceedings of the National Academy of Sciences, India Section B: Biologic… https://link.springer.com/article/10.1007/s40011-024-01658-5 2/13