Research: COVID-19 Virus

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https://africarxiv.ubuntunet.net/handle/1/1388

Research that investigated genetic mutation and the clinical significance of possible mutations.

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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.
Large-Scale Synthesis of CISe/ZnS Core-Shell Quantum Dots and Its Effects on the Enzymatic Activity of Recombinant Human Furin (an Activator of SARS-CoV-2 S1/S2 Spike Proteins)
(2023) Ncapayi, Vuyelwa; Famutimi, Oladoyin Grace; Lebepe, Thabang Calvin ; Maluleke, Rodney; Masha, Sam; Mgedle, Nande; Parani, Sundararajan; Kodama, Tetsuya; Adewale, Isaac Olusanjo ; Oluwafemi, Oluwatobi Samuel
We herein report, for the first time, the activity of copper indium selenide/zinc sulphide core-shell quantum dots (CISe/ZnS QDs) as an inhibitor against recombinant human furin, an enzyme that has been implicated in the aetiology of many diseases, including Covid-19. The cell viability of the as-synthesised CISe/ZnS QDs was tested against mouse colon carcinoma cells (C26), while the Furin activity was measured by hydrolysis of peptide substrate Pyr-RTKR-AMC liberating the fluorogenic 7-amino-4-methyl coumarin. The result showed that the as-synthesised stable near-infrared emitting (840 nm) CISe-ZnS QDs is biocompatible against C26 and can inhibit furin with an inhibition constant, Ki, of 15.66 μM. The IC50 was 11.29 ± 0.54 μM, while the enzymatic activity was abolished at about 23 μM of the inhibitor concentration. The results indicate the chemotherapeutic potential of CISe-ZnS QDs as an enzyme inhibitor, which may find application in managing diseases whose pathogenesis involves hyperactivity of furin.
Comparative analysis of the antibody titers to different SARS-COV-2 vaccines in vaccinated tertiary students in Botswana
(2023) Maswabi, Bokang
Rapidly evolving new variants of SARS-CoV-2, e.g., alpha, beta, delta and omicron, were associated with higher transmissibility and pathogenicity causing new waves of infections in most countries. During the Covid-19 pandemic Botswana like most countries in Africa initiated a rigorous vaccine program to protect its population. Due to the dynamics of vaccine availability Botswana engaged in a heterologous mix and match vaccine strategy which relied on using generally available vaccines while. The country prioritised vulnerable citizens. Hence subjects received various vaccines and in various regimen in both Homologous and heterologous combinations. In Botswana, the administered vaccines included inactivated virus-based vaccines Sinovac/CoronaVac, mRNA-based vaccines Pfizer-BioNTech and Moderna and lastly viral vector-based vaccines AstraZeneca and Janssen by Johnson & Johnson. These vaccines stimulate immune responses, including B-cell (humoral/antibody) activation with subsequent production of antibodies (IgM, IgG, IgA) [2,3,4]. Research work was done to analyse and quantify induced antibody titers (IgM and IgG) in vaccinated and non-vaccinated individuals during the Covid-19 pandemic. We also enrolled participants in a longitudinal cohort-based sero-epidemiological survey to quantify the proportion of subjects who were seropositive at various points during Covid-19 pandemic.
Kinetics of trypsin inhibition by methanolic and solvent-partitioned fractions of two medicinal plants – Momordica charantia and Xylopia aethiopica
(2023-01-15) Adewale, Isaac Olusanjo; Adebiyi, Victor Gbolahan; Famutimi, Oladoyin Grace; Dada, Omoniyi Vincent
An Odyssey into the World of Enzymes
(2023-03-14) Adewale, Isaac Olusanjo
An Inaugural Lecture Delivered at Oduduwa Hall, Obafemi Awolowo University, Ile-Ife, Nigeria on Tuesday, 14th March, 2023 by Isaac Olusanjo Adewale, Professor of Biochemistry Inaugural Lecture Series 369
Inhibition Characteristics of Peptide Extracts of Four Medicinal Plants on Activities of Bovine Trypsin
(Elsevier, 2023-07-04) Famutimi, Oladoyin Grace ; Adewale, Isaac Olusanjo; Adegoke, Kehinde Rofiat
Aqueous extract of leaves of Momordica charantia, Hymenocardia acida, Lawsonia inermis and fruit of Xylopia aethiopica have been used in sub Saharan Africa in the management of many viral diseases. Their medicinal properties had been reported to be due to their high antioxidant activities, but limited information is available whether these properties are also due to inhibition or modulation of proteases important in the pathology of viral infections. We report the inhibitory characteristics of peptides extracted from these medicinal plants against bovine trypsin, a serine protease. Extraction of the peptides was done using standard procedure and their inhibitory activities were measured against bovine trypsin. Aqueous extract of M. charantia, H. acida, L. inermis and X. aethiopica contain 5.7 ± 0.5 mg/ml, 1.0 ± 0.2 mg/ml, 1.8 ± 0.1 mg/ml and 28.3 ± 4.1 mg/ml of peptides, respectively. Using Nα-benzoyl-DL-arginine 4-nitroanilide (BAPNA) as trypsin substrate, a Km and Vmax of 0.34 mM and 0.6 μmole/min/mg protein obtained, were altered in the presence of the peptide extracts suggesting the extracts modulate trypsin activity. The inhibition was either competitive, non-competitive or mixed-type of non-competitive inhibition. Inhibition constant (Ki) ranging from 81 to 831±120 μg/ml were obtained using Dixon plot with the peptide extract from M. charantia being the most potent. We concluded that the medicinal and antiviral properties of the extracts could also be due to inhibition or modulation of proteases involved in the pathology of viral infection.
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
Validation and field operationalization of one- and two-stage LAMP assay for diagnosis of COVID-19 in low-resourced health facilities in Ghana (VoLCOV)
(2024-07-09) Akorli, Jewelna
The rapid spread of the novel coronavirus disease, COVID-19, necessitates early detection of infected persons as part of strategies to identify and control community transmission. Testing for COVID-19 remain important especially for frontline workers, other high-risk groups and travellers. Although testing methods are available there remains avenues for improving and increasing the capacity to test and detect the virus.
Validation of cheap Sample Processing Methods and LAMP Assay for COVID-19 Diagnosis
(2024-07-09) Opoku, Millicent; Aboagye, Elizabeth; Yusif Ismail, Rahmat; Bonney, Joseph Humphrey Kofi; SYLVERKEN, AUGUSTINA; Song, Jinzhao; Akorli, Jewelna
Evaluate and validate cheap sample processing methods and Lamp Assays for diagnosis of Covid 19

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