21 results on '"Shapi M"'
Search Results
2. Promising inhibitors against main protease of SARS CoV-2 from medicinal plants: In silico identification
- Author
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EBENEZER OLUWAKEMI and SHAPI MICHAEL
- Subjects
sars cov-2 main protease inhibitors ,medicinal plants ,molecular docking ,admet properties ,Pharmaceutical industry ,HD9665-9675 - Abstract
Some compounds reported as active against SARS CoV were selected, and docking studies were performed using the main protease of SARS CoV-2 as the receptor. The docked complex analysis shows that the ligands selectively bind with the target residues and binding affinity of amentoflavone (–10.1 kcal mol–1), isotheaflavin-3’-gallate (–9.8 kcal mol–1), tomentin A and D (–8.0 and –8.8 kcal mol–1), theaflavin-3,3’-digallate (–8.6 kcal mol–1), papyriflavonol A (–8.4 kcal mol–1), iguesterin (–8.0 kcal mol–1) and savinin (–8.3 kcal mol–1) were ranked above the binding affinity of the reference, co-crystal ligand, ML188, a furan-2-carboxamide-based compound. To pinpoint the drug-like compound among the top-ranked compounds, the Lipinski’s rule of five and pharmacokinetic properties of all the selected compounds were evaluated. The results detailed that savinin exhibits high gastrointestinal absorption and can penetrate through the blood-brain barrier. Also, modifying these natural scaffolds with excellent binding affinity may lead to discovering of anti-SARS CoV agents with promising safety profiles.
- Published
- 2022
- Full Text
- View/download PDF
3. Medicinal plants with anti-SARS-CoV activity repurposing for treatment of COVID-19 infection: A systematic review and meta-analysis
- Author
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EBENEZER OLUWAKEMI, BODEDE OLUSOLA, AWOLADE PAUL, JORDAAN MARYAM A., OGUNSAKIN ROPO E., and SHAPI MICHAEL
- Subjects
covid-19 main protease ,inhibition ,medicinal plants ,systematic review ,meta-analysis ,Pharmaceutical industry ,HD9665-9675 - Abstract
The novel SARS-CoV-2 (severe acute respiratory syndrome coronavirus) has emerged as a significant threat to public health with startling drawbacks in all sectors globally. This study investigates the practicality of some medicinal plants for SARS-CoV-2 therapy using a systematic review and meta-analysis of their reported SARS-CoV-1 inhibitory potencies. Relevant data were systematically gathered from three databases, viz., Web of Science, PubMed and Scopus. The information obtained included botanical information, extraction method and extracts concentrations, as well as the proposed mechanisms. Fourteen articles describing 30 different plants met our eligibility criteria. Random effects model and subgroup analysis were applied to investigate heterogeneity. According to subgroup analysis, the substantial heterogeneity of the estimated mean based on the IC50 values reporting the most potent anti-SARS-CoV 3C--like protease (3CLpro) inhibitors (10.07 %, p < 0.0001), was significantly higher compared to the most active anti-SARS-CoV papain-like protease (PLpro) inhibitors (6.12 %, p < 0.0001). More importantly, the literature analysis revealed that fruit extracts of Rheum palmatum L. and the compound cryptotanshinone isolated from the root of Salvia miltiorrhiza (IC50 = 0.8 ± 0.2 μmol L–1) were excellent candidates for anti--SARS-CoV targeting PLpro. Meanwhile, iguesterin (IC50 = 2.6 ± 0.6 μmol L–1) isolated from the bark of Tripterygium regelii emerged as the most excellent candidate for anti-SARS--CoV targeting 3CLpro. The present systematic review and meta-analysis provide valuable and comprehensive information about potential medicinal plants for SARS-CoV-2 inhibition. The chemotypes identified herein can be adopted as a starting point for developing new drugs to contain the novel virus.
- Published
- 2022
- Full Text
- View/download PDF
4. Background Concentrations of Potentially Harmful Elements in Soils of the Kette-Batouri Region, Eastern Cameroon
- Author
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Jordaan, M.A., primary, Edith-Etak, B.T., additional, Shapi, M., additional, Penaye, J., additional, Mimba, M.E., additional, NguemheFil, S.C., additional, Nadasan, D.S., additional, and Davies, T.C., additional
- Published
- 2016
- Full Text
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5. Baseline measures of primary health care team functioning and overall primary health care performance at Du Noon Community Health Centre
- Author
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Shapi Mukiapini, Graham Bresick, Abdul-Rauf Sayed, and Cynthia Le grange
- Subjects
primary health care team ,Medicine ,Public aspects of medicine ,RA1-1270 - Abstract
Background: Research consistently demonstrates the importance of effective team work for improving the quality of health care. We conducted a baseline measure of primary health care (PHC) team effectiveness and overall PHC performance at a primary care facility. Aim: To improve PHC team effectiveness and ultimately the quality and user experience of primary care at a community health centre (CHC). Setting: Du Noon CHC in the southern and western substructure of the Cape Town Metro district services (MDHS). Methods: A cross-sectional study using a combination of the Nominal Group Technique (NGT) consensus method and the South African Primary Care Assessment Tool (ZA PCAT) to assess PHC team effectiveness and PHC organisation and performance. Results: The ZA PCAT was administered to 110 CHC users (patients) and 12 providers (doctors and clinical nurse practitioners). Data from 20 PHC team members showed they perceived their team as well functioning (70% agreement on a 7-item PHC team assessment tool incorporated into the ZA PCAT). The NGT method achieved participant (20) consensus on communication and leadership as the main challenges to effective team functioning and on ideas to overcome the challenges. The ZA PCAT user data showed 18.2% of users rated first contact access as acceptable to good; 47.3% of users rated ongoing care as acceptable to good. Provider data showed that 33% of providers rated first contact access as acceptable to good; 25% of providers rated ongoing care as acceptable to good. First contact access received the lowest acceptable to good score (18.2%) and comprehensiveness (services available) the highest score (88.2%) from users. For the providers, the lowest acceptable to good score was for ongoing care (25%) and the highest acceptable to good score was for primary health care team availability (100%). The ZA PCAT total primary scores were good (above 60%) for both users and providers but moderately higher for the providers. Conclusion: Knowledge of how teams perceive their effectiveness can motivate them to generate ideas for improving performance. There were discrepancies between providers’ assessment of team functioning using the ZA PCAT measure and the NGT method results. The ZA PCAT also showed differences between providers’ and users’ perceptions of PHC performance – consistent with the findings of the multi-CHC Western Cape ZA PCAT study. These findings should encourage and support CHC and district level staff in their efforts to improve the quality and user experience of primary care, as well as PHC team performance.
- Published
- 2018
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6. Ethnobotanical study of indigenous knowledge on medicinal plant use by traditional healers in Oshikoto region, Namibia
- Author
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Mu Ashekele Hina, Matengu Kenneth, Shapi Martin, and Cheikhyoussef Ahmad
- Subjects
Other systems of medicine ,RZ201-999 ,Botany ,QK1-989 - Abstract
Abstract Background The objective of this study was to establish a regional profile of the indigenous knowledge system (IKS) for medicinal plant use and cultural practices associated with the healing process of these plants by traditional healers in the Oshikoto region, Namibia. Methods An ethnobotanical survey was undertaken to collect information from traditional healers during September and October 2008. Data was collected through the use of questionnaires and personal interviews during field trips in the ten constituencies of the Oshikoto region. A total of 47 respondents were interviewed with most of them aged 66 and above. Results The traditional healers in Oshikoto region use 61 medicinal plant species that belong to 25 families for the treatment of various diseases and disorders with the highest number of species being used for mental diseases followed by skin infection and external injuries. Trees (28 species) were found to be the most used plants followed by herbs (15 species), shrubs (10 species) and climbers (4 species). The average of the informant consensus factor (FIC) value for all ailment categories was 0.75. High FIC values were obtained for Pergularia daemia, and Tragia okanyua, which were reported to treat weakness and dizziness problems, snake bite, swelling and cardiovascular problems indicating that these species traditionally used to treat these ailments are worth examining for bioactive compounds. Conclusions The traditional healers in Oshikoto possess rich ethno-pharmacological knowledge. This study allows for identifying many high value medicinal plant species, indicating high potential for economic development through sustainable collection of these medicinal plants.
- Published
- 2011
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7. A Molecular Docking Study Reveals That Short Peptides Induce Conformational Changes in the Structure of Human Tubulin Isotypes αβI, αβII, αβIII and αβIV.
- Author
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Ebenezer O, Damoyi N, Shapi M, Wong GK, and Tuszynski JA
- Abstract
Microtubules are cylindrical protein polymers assembled in the cytoplasm of all eukaryotic cells by polymerization of aβ tubulin dimers, which are involved in cell division, migration, signaling, and intracellular traffic. These functions make them essential in the proliferation of cancerous cells and metastases. Tubulin has been the molecular target of many anticancer drugs because of its crucial role in the cell proliferation process. By developing drug resistance, tumor cells severely limit the successful outcomes of cancer chemotherapy. Hence, overcoming drug resistance motivates the design of new anticancer therapeutics. Here, we retrieve short peptides obtained from the data repository of antimicrobial peptides (DRAMP) and report on the computational screening of their predicted tertiary structures for the ability to inhibit tubulin polymerization using multiple combinatorial docking programs, namely PATCHDOCK, FIREDOCK, and ClusPro. The interaction visualizations show that all the best peptides from the docking analysis bind to the interface residues of the tubulin isoforms αβl, αβll, αβlll, and αβlV, respectively. The docking studies were further confirmed by a molecular dynamics simulation, in which the computed root-mean-square deviation (RMSD), and root-mean-square fluctuation (RMSF), verified the stable nature of the peptide-tubulin complexes. Physiochemical toxicity and allergenicity studies were also performed. This present study suggests that these identified anticancer peptide molecules might destabilize the tubulin polymerization process and hence can be suitable candidates for novel drug development. It is concluded that wet-lab experiments are needed to validate these findings.
- Published
- 2023
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8. An Overview of the Biological Evaluation of Selected Nitrogen-Containing Heterocycle Medicinal Chemistry Compounds.
- Author
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Ebenezer O, Jordaan MA, Carena G, Bono T, Shapi M, and Tuszynski JA
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- Drug Discovery, Nitrogen, Triazoles chemistry, Chemistry, Pharmaceutical, Heterocyclic Compounds chemistry, Heterocyclic Compounds pharmacology
- Abstract
Heterocyclic compounds are a class of compounds of natural origin with favorable properties and hence have major pharmaceutical significance. They have an exceptional adroitness favoring their use as diverse smart biomimetics, in addition to possessing an active pharmacophore in a complex structure. This has made them an indispensable motif in the drug discovery field. Heterocyclic compounds are usually classified according to the ring size, type, and the number of heteroatoms present in the ring. Among different heterocyclic ring systems, nitrogen heterocyclic compounds are more abundant in nature. They also have considerable pharmacological significance. This review highlights recent pioneering studies in the biological assessment of nitrogen-containing compounds, namely: triazoles, tetrazoles, imidazole/benzimidazoles, pyrimidines, and quinolines. It explores publications between April 2020 and February 2022 and will benefit researchers in medicinal chemistry and pharmacology. The present work is organized based on the size of the heterocyclic ring.
- Published
- 2022
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9. Mapping Scientific Productivity Trends and Hotspots in Remdesivir Research Publications: A Bibliometric Study from 2016 to 2021.
- Author
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Ogunsakin RE, Ebenezer O, Jordaan MA, Shapi M, and Ginindza TG
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- Databases, Factual, Efficiency, Global Health, Publications trends, Adenosine Monophosphate analogs & derivatives, Alanine analogs & derivatives, Bibliometrics
- Abstract
In response to global efforts to control and exterminate infectious diseases, this study aims to provide insight into the productivity of remdesivir research and highlight future directions. To achieve this, there is a need to summarize and curate evidence from the literature. As a result, this study carried out comprehensive scientific research to detect trends in published articles related to remdesivir using a bibliometric analysis. Keywords associated with remdesivir were used to access pertinent published articles using the Scopus database. A total of 5321 research documents were retrieved, primarily as novel research articles ( n = 2440; 46%). The number of publications increased exponentially from 2020 up to the present. The papers published by the top 12 institutions focusing on remdesivir accounted for 25.69% of the overall number of articles. The USA ranked as the most productive country, with 906 documents (37.1%), equivalent to one-third of the global publications in this field. The most productive institution was Icahn School of Medicine, Mount Sinai, in the USA (103 publications). The New England Journal of Medicine was the most cited, with an h -index of 13. The publication of research on remdesivir has gained momentum in the past year. The importance of remdesivir suggests that it needs continued research to help global health organizations detect areas requiring instant action to implement suitable measures. Furthermore, this study offers evolving hotspots and valuable insights into the scientific advances in this field and provides scaling-up analysis and evidence diffusion on remdesivir.
- Published
- 2022
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10. A Review of the Recent Development in the Synthesis and Biological Evaluations of Pyrazole Derivatives.
- Author
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Ebenezer O, Shapi M, and Tuszynski JA
- Abstract
Pyrazoles are five-membered heterocyclic compounds that contain nitrogen. They are an important class of compounds for drug development; thus, they have attracted much attention. In the meantime, pyrazole derivatives have been synthesized as target structures and have demonstrated numerous biological activities such as antituberculosis, antimicrobial, antifungal, and anti-inflammatory. This review summarizes the results of published research on pyrazole derivatives synthesis and biological activities. The published research works on pyrazole derivatives synthesis and biological activities between January 2018 and December 2021 were retrieved from the Scopus database and reviewed accordingly.
- Published
- 2022
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11. A Review of the Recent Developments of Molecular Hybrids Targeting Tubulin Polymerization.
- Author
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Ebenezer O, Shapi M, and Tuszynski JA
- Subjects
- Humans, Microtubules metabolism, Mitosis, Polymerization, Tubulin Modulators chemistry, Neoplasms drug therapy, Neoplasms metabolism, Tubulin metabolism
- Abstract
Microtubules are cylindrical protein polymers formed from α -tubulin heterodimers in the cytoplasm of eukaryotic cells. Microtubule disturbance may cause cell cycle arrest in the G2/M phase, and anomalous mitotic spindles will form. Microtubules are an important target for cancer drug action because of their critical role in mitosis. Several microtubule-targeting agents with vast therapeutic advantages have been developed, but they often lead to multidrug resistance and adverse side effects. Thus, single-target therapy has drawbacks in the effective control of tubulin polymerization. Molecular hybridization, based on the amalgamation of two or more pharmacophores of bioactive conjugates to engender a single molecular structure with enhanced pharmacokinetics and biological activity, compared to their parent molecules, has recently become a promising approach in drug development. The practical application of combined active scaffolds targeting tubulin polymerization inhibitors has been corroborated in the past few years. Meanwhile, different designs and syntheses of novel anti-tubulin hybrids have been broadly studied, illustrated, and detailed in the literature. This review describes various molecular hybrids with their reported structural-activity relationships (SARs) where it is possible in an effort to generate efficacious tubulin polymerization inhibitors. The aim is to create a platform on which new active scaffolds can be modeled for improved tubulin polymerization inhibitory potency and hence, the development of new therapeutic agents against cancer.β -tubulin heterodimers in the cytoplasm of eukaryotic cells. Microtubule disturbance may cause cell cycle arrest in the G2/M phase, and anomalous mitotic spindles will form. Microtubules are an important target for cancer drug action because of their critical role in mitosis. Several microtubule-targeting agents with vast therapeutic advantages have been developed, but they often lead to multidrug resistance and adverse side effects. Thus, single-target therapy has drawbacks in the effective control of tubulin polymerization. Molecular hybridization, based on the amalgamation of two or more pharmacophores of bioactive conjugates to engender a single molecular structure with enhanced pharmacokinetics and biological activity, compared to their parent molecules, has recently become a promising approach in drug development. The practical application of combined active scaffolds targeting tubulin polymerization inhibitors has been corroborated in the past few years. Meanwhile, different designs and syntheses of novel anti-tubulin hybrids have been broadly studied, illustrated, and detailed in the literature. This review describes various molecular hybrids with their reported structural-activity relationships (SARs) where it is possible in an effort to generate efficacious tubulin polymerization inhibitors. The aim is to create a platform on which new active scaffolds can be modeled for improved tubulin polymerization inhibitory potency and hence, the development of new therapeutic agents against cancer.
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- 2022
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12. Unveiling of Pyrimidindinones as Potential Anti-Norovirus Agents-A Pharmacoinformatic-Based Approach.
- Author
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Ebenezer O, Damoyi N, Jordaan MA, and Shapi M
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- Humans, Hydrogen Bonding, Protein Binding, Pyrimidines chemistry, Pyrimidines pharmacology, Antiviral Agents pharmacology, Antiviral Agents chemistry, Molecular Docking Simulation, Norovirus drug effects, Molecular Dynamics Simulation, RNA-Dependent RNA Polymerase chemistry, RNA-Dependent RNA Polymerase antagonists & inhibitors, RNA-Dependent RNA Polymerase metabolism
- Abstract
The RNA-dependent RNA polymerase (RdRp) receptor is an attractive target for treating human norovirus (HNV). A computer-aided approach like e-pharmacophore, molecular docking, and single point energy calculations were performed on the compounds retrieved from the Development Therapeutics Program (DTP) AIDS Antiviral Screen Database to identify the antiviral agent that could target the HNV RdRp receptor. Induced-fit docking (IFD) results showed that compounds ZINC1617939, ZINC1642549, ZINC6425208, ZINC5887658 and ZINC32068149 bind with the residues in the active site-B of HNV RdRp receptor via hydrogen bonds, salt bridge, and electrostatic interactions. During the molecular dynamic simulations, compounds ZINC6425208, ZINC5887658 and ZINC32068149 displayed an unbalanced backbone conformation with HNV RdRp protein, while ZINC1617939 and ZINC1642549 maintained stability with the protein backbone when interacting with the residues. Hence, the two new concluding compounds discovered by the computational approach can be used as a chemotype to design promising antiviral agents aimed at HNV RdRp.
- Published
- 2022
- Full Text
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13. Medicinal plants with anti-SARS-CoV activity repurposing for treatment of COVID-19 infection: A systematic review and meta-analysis.
- Author
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Ebenezer O, Bodede O, Awolade P, Jordaan MA, Ogunsakin RE, and Shapi M
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- Humans, SARS-CoV-2, Drug Repositioning, Protease Inhibitors, Peptide Hydrolases, Antiviral Agents pharmacology, Antiviral Agents therapeutic use, COVID-19, Plants, Medicinal
- Abstract
The novel SARS-CoV-2 (severe acute respiratory syndrome coronavirus) has emerged as a significant threat to public health with startling drawbacks in all sectors globally. This study investigates the practicality of some medicinal plants for SARS-CoV-2 therapy using a systematic review and meta-analysis of their reported SARS-CoV-1 inhibitory potencies. Relevant data were systematically gathered from three databases, viz. , Web of Science, PubMed and Scopus. The information obtained included botanical information, extraction method and extracts concentrations, as well as the proposed mechanisms. Fourteen articles describing 30 different plants met our eligibility criteria. Random effects model and subgroup analysis were applied to investigate heterogeneity. According to subgroup analysis, the substantial heterogeneity of the estimated mean based on the IC
50 values reporting the most potent anti-SARS-CoV 3C--like protease (3CLpro) inhibitors (10.07 %, p < 0.0001), was significantly higher compared to the most active anti-SARS-CoV papain-like protease (PLpro) inhibitors (6.12 %, p < 0.0001). More importantly, the literature analysis revealed that fruit extracts of Rheum palmatum L. and the compound cryptotanshinone isolated from the root of Salvia miltiorrhiza ( IC50 = 0.8 ± 0.2 μmol L-1 ) were excellent candidates for anti--SARS-CoV targeting PLpro. Meanwhile, iguesterin ( IC50 = 2.6 ± 0.6 μmol L-1 ) isolated from the bark of Tripterygium regelii emerged as the most excellent candidate for anti-SARS--CoV targeting 3CLpro. The present systematic review and meta-analysis provide valuable and comprehensive information about potential medicinal plants for SARS-CoV-2 inhibition. The chemotypes identified herein can be adopted as a starting point for developing new drugs to contain the novel virus., (© 2022 Oluwakemi Ebenezer., published by Sciendo.)- Published
- 2021
- Full Text
- View/download PDF
14. Promising inhibitors against main protease of SARS CoV-2 from medicinal plants: In silico identification.
- Author
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Ebenezer O and Shapi M
- Subjects
- SARS-CoV-2, Peptide Hydrolases, Molecular Docking Simulation, Protease Inhibitors pharmacology, Plants, Medicinal, COVID-19
- Abstract
Some compounds reported as active against SARS CoV were selected, and docking studies were performed using the main protease of SARS CoV-2 as the receptor. The docked complex analysis shows that the ligands selectively bind with the target residues and binding affinity of amentoflavone (-10.1 kcal mol
-1 ), isotheaflavin-3'-gallate (-9.8 kcal mol-1 ), tomentin A and D (-8.0 and -8.8 kcal mol-1 ), theaflavin-3,3'-digallate (-8.6 kcal mol-1 ), papyriflavonol A (-8.4 kcal mol-1 ), iguesterin (-8.0 kcal mol-1 ) and savinin (-8.3 kcal mol-1 ) were ranked above the binding affinity of the reference, co-crystal ligand, ML188, a furan-2-carboxamide-based compound. To pinpoint the drug-like compound among the top-ranked compounds, the Lipinski's rule of five and pharmacokinetic properties of all the selected compounds were evaluated. The results detailed that savinin exhibits high gastrointestinal absorption and can penetrate through the blood-brain barrier. Also, modifying these natural scaffolds with excellent binding affinity may lead to discovering of anti-SARS CoV agents with promising safety profiles., (© 2022 Oluwakemi Ebenezer., published by Sciendo.)- Published
- 2021
- Full Text
- View/download PDF
15. Predicting New Anti-Norovirus Inhibitor With the Help of Machine Learning Algorithms and Molecular Dynamics Simulation-Based Model.
- Author
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Ebenezer O, Damoyi N, and Shapi M
- Abstract
Hepatitis C virus (HCV) inhibitors are essential in the treatment of human norovirus (HuNoV). This study aimed to map out HCV NS5B RNA-dependent RNA polymerase inhibitors that could potentially be responsible for the inhibitory activity of HuNoV RdRp. It is necessary to develop robust machine learning and in silico methods to predict HuNoV RdRp compounds. In this study, Naïve Bayesian and random forest models were built to categorize norovirus RdRp inhibitors from the non-inhibitors using their molecular descriptors and PubChem fingerprints. The best model observed had accuracy, specificity, and sensitivity values of 98.40%, 97.62%, and 97.62%, respectively. Meanwhile, an external test set was used to validate model performance before applicability to the screened HCV compounds database. As a result, 775 compounds were predicted as NoV RdRp inhibitors. The pharmacokinetics calculations were used to filter out the inhibitors that lack drug-likeness properties. Molecular docking and molecular dynamics simulation investigated the inhibitors' binding modes and residues critical for the HuNoV RdRp receptor. The most active compound, CHEMBL167790, closely binds to the binding pocket of the RdRp enzyme and depicted stable binding with RMSD 0.8-3.2 Å, and the RMSF profile peak was between 1.0-4.0 Å, and the conformational fluctuations were at 450-460 residues. Moreover, the dynamic residue cross-correlation plot also showed the pairwise correlation between the binding residues 300-510 of the HuNoV RdRp receptor and CHEMBL167790. The principal component analysis depicted the enhanced movement of protein atoms. Moreover, additional residues such as Glu510 and Asn505 interacted with CHEMBL167790 via water bridge and established H-bond interactions after the simulation. http://zinc15.docking.org/substances/ZINC000013589565., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ebenezer, Damoyi and Shapi.)
- Published
- 2021
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16. Discovery of Potential Inhibitors for RNA-Dependent RNA Polymerase of Norovirus: Virtual Screening, and Molecular Dynamics.
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Ebenezer O, Jordaan MA, Damoyi N, and Shapi M
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- Computer Simulation, Humans, Structure-Activity Relationship, Antiviral Agents pharmacology, Drug Discovery, Enzyme Inhibitors pharmacology, Molecular Dynamics Simulation, Norovirus drug effects, RNA-Dependent RNA Polymerase antagonists & inhibitors, Viral Proteins antagonists & inhibitors
- Abstract
Noroviruses are non-enveloped viruses with a positive-sense single-stranded RNA (ssRNA) genome belonging to the genus Norovirus , from the family Caliciviridae, which are accountable for acute gastroenteritis in humans. The Norovirus genus is subdivided into seven genogroups, i.e., (GI-GVII); among these, the genogroup II and genotype 4 (GII.4) strains caused global outbreaks of human norovirus (HuNov) disease. The viral genome comprises three open reading frames (ORFs). ORF1 encodes the nonstructural polyprotein that is cleaved into six nonstructural proteins, which include 3C-like cysteine protease (3CLpro) and a viral RNA-dependent RNA polymerase. ORF2 and ORF3 encode the proteins VP1 and VP2. The RNA-dependent RNA polymerase (RdRp) from noroviruses is one of the multipurpose enzymes of RNA viruses vital for replicating and transcribing the viral genome, making the virally encoded enzyme one of the critical targets for the development of novel anti-norovirus agents. In the quest for a new antiviral agent that could combat HuNov, high throughput virtual screening (HTVS), combined with e-pharmacophore screening, was applied to screen compounds from the PubChem database. CMX521 molecule was selected as a prototype for a similarity search in the PubChem online database. Molecular dynamics simulations were employed to identify different compounds that may inhibit HuNov. The results predicted that compound CID-57930781 and CID-44396095 formed stable complexes with MNV-RdRp within 50 ns; hence, they may signify as promising human norovirus inhibitors.
- Published
- 2020
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17. Virtual screening, molecular docking studies and DFT calculations of FDA approved compounds similar to the non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz.
- Author
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Jordaan MA, Ebenezer O, Damoyi N, and Shapi M
- Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was confirmed as the causative virus of COVID-19 disease, which is currently a worldwide pandemic. Efavirenz, a non-nucleoside reverse transcriptase inhibitor (NNRTI), is one of the most potent chemical compounds proposed to treat COVID-19 infection. We, therefore, performed virtual screening on FDA approved drugs that are similar to the efavirenz moiety. Subsequently, the compounds were subjected to screening by analyzing their drug-likeness, such as Lipinski's rule of five and ADMET properties. Molecular docking study revealed that Met165, His41, His163, and Phe140 were important interacting residues for COVID-19 main protease receptor-ligand interaction. Five top-ranked compounds, podophyllotoxin, oxacillin, lovastatin, simvastatin, and gefitinib, were selected by virtual screening and docking studies. The highest occupied molecular (HOMO) orbital, lowest unoccupied molecular orbital (LUMO) and energy gap values was calculated using density functional theory (DFT). The results of the study showed that lovastatin and simvastatin might be considered as lead compounds for further development for COVID-19 main protease inhibitors., (© 2020 The Author(s).)
- Published
- 2020
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18. Potential SARS-COV preclinical (in vivo) compounds targeting COVID-19 main protease: a meta-analysis and molecular docking studies.
- Author
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Ebenezer O, Jordaan MA, Ogunsakin RE, and Shapi M
- Abstract
Background: Due to the migratory flow of infected people with severe acute respiratory syndrome virus (SARS COV-2), the number of confirmed cases of coronavirus disease 2019 (COVID-19) is accelerating globally; preclinical evidence of antiviral agents that can combat this pandemic is still elusive. We identified published articles on SARS-COV efficacy experiments in which some selected compounds were used to test the reduction of the virus load in mice., Methods: A systematic search of articles was conducted in PubMed, Web of Science, and Scopus. We then developed a combined model based on a systematic review, meta-analyses, and molecular docking studies to evaluate the effect size of preclinical studies of compounds that have been tested against SARS-COV. Because substantial heterogeneity was expected, random effect model meta-analyses were carried out to estimate the overall pooled disease's prevalence. All meta-analyses were performed with Stata version 15.0. Subgroup analyses on therapies were conducted as well. Molecular docking studies of the inhibitors in the active pocket of COVID-19 protease were also performed., Results: From all screened articles, six studies were appropriate for ultimate meta-analysis and systematic review. The residual amount of heterogeneity was high (τ
2 =0.02; heterogeneity I2 =85.5 % with heterogeneity chi-square =103.57, a degree of freedom =15, and p <0.001). The overall random pooled prevalence of infected mice treated with the selected compounds was 78.1 % [95 % Confidence Interval (CI): 14.7-17.0 %]. Prophylactic has a significantly higher pooled prevalence than therapeutic, with 21.8 % (95 % CI: 16.4 % to 28.8 %). Our results indicated that most of the SARS-COV inhibitors analyzed were less effective in reducing the lung virus titer of SARS-COV infection in animal models. The findings from molecular docking studies also identified COVID-19 inhibitors that are good for optimization and drug development to fight against COVID-19 infection., Conclusions: Findings from the review showed that studies on the preclinical compounds targeting SARS-COV and COVID-19 are limited. Furthermore, molecular docking studies and meta-analysis results substantiated three compounds, i.e., EIDD-2801, GS-5734, and amodiaquine. HIPPOKRATIA 2020, 24(3): 99-106., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright 2020, Hippokratio General Hospital of Thessaloniki.)- Published
- 2020
19. Investigation of the solvent-dependent photolysis of a nonnucleoside reverse-transcriptase inhibitor, antiviral agent efavirenz.
- Author
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Jordaan MA and Shapi M
- Subjects
- Alkynes, Anti-HIV Agents pharmacology, Benzoxazines pharmacology, Cyclopropanes, HIV drug effects, Microbial Sensitivity Tests, Molecular Conformation, Reverse Transcriptase Inhibitors pharmacology, Solvents chemistry, Anti-HIV Agents chemistry, Benzoxazines chemistry, Photolysis, Reverse Transcriptase Inhibitors chemistry
- Abstract
This study sought to investigate the solvent-dependency on the photolysis of efavirenz to gain insight into the photoprocesses involved. The primary mechanisms were firstly the excited-state intramolecular proton transfer (i.e. phototautomerization), which generated the imidic acid phototautomer observed as [M-H]
- quasimolecular ion at m/z 314.0070 in the high-performance liquid chromatography-electrospray ionization-time-of-flight mass spectrometry in the negative mode. Secondly, the photoinduced α-cleavage with the loss of a carbonyl group occurred (i.e. photodecarbonylation) to form the photoproduct at m/z 286.0395. The ultraviolet-visible spectra illustrated a large, hyperchromic, and slight bathochromic effect in both the π→π* and n→π* electronic transitions. The largest bathochromic effect was prevalent in the chloroform solvent, i.e. chloroform (π* = 0.58; β = 0.00; α = 0.44) > methanol (π* = 0.60; β = 0.66; α = 0.98) > acetonitrile (π* = 0.75; β = 0.40; α = 0.19). This is due to the significant interaction of the amino group with the excited carbonyl moiety which is attributed to intramolecular phototautomerization resulting in a larger energy shift of the electronic state. A plausible explanation is due to the hydrogen bond donor ability of the polar methanol and nonpolar chloroform solvents, which stabilized the polarized imidic acid phototautomer by means of hydrogen bonding interactions, as opposed to the aprotic acetonitrile which exhibits no hydrogen bonding interactions. The study would form the basis for further photolytic analyses and syntheses to generate a plethora of novel photoproducts with anti-HIV activity based on the biologically active benzoxazinone framework of efavirenz.- Published
- 2017
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20. Ethnobotanical study of indigenous knowledge on medicinal plant use by traditional healers in Oshikoto region, Namibia.
- Author
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Cheikhyoussef A, Shapi M, Matengu K, and Ashekele HM
- Subjects
- Adult, Aged, Cultural Characteristics, Ethnobotany, Female, Humans, Male, Middle Aged, Namibia, Qualitative Research, Clinical Competence, Medicine, Traditional, Phytotherapy methods, Plants, Medicinal classification
- Abstract
Background: The objective of this study was to establish a regional profile of the indigenous knowledge system (IKS) for medicinal plant use and cultural practices associated with the healing process of these plants by traditional healers in the Oshikoto region, Namibia., Methods: An ethnobotanical survey was undertaken to collect information from traditional healers during September and October 2008. Data was collected through the use of questionnaires and personal interviews during field trips in the ten constituencies of the Oshikoto region. A total of 47 respondents were interviewed with most of them aged 66 and above., Results: The traditional healers in Oshikoto region use 61 medicinal plant species that belong to 25 families for the treatment of various diseases and disorders with the highest number of species being used for mental diseases followed by skin infection and external injuries. Trees (28 species) were found to be the most used plants followed by herbs (15 species), shrubs (10 species) and climbers (4 species). The average of the informant consensus factor (F IC) value for all ailment categories was 0.75. High F IC values were obtained for Pergularia daemia, and Tragia okanyua, which were reported to treat weakness and dizziness problems, snake bite, swelling and cardiovascular problems indicating that these species traditionally used to treat these ailments are worth examining for bioactive compounds., Conclusions: The traditional healers in Oshikoto possess rich ethno-pharmacological knowledge. This study allows for identifying many high value medicinal plant species, indicating high potential for economic development through sustainable collection of these medicinal plants.
- Published
- 2011
- Full Text
- View/download PDF
21. Gas chromatographic-mass spectrometric analysis of some potential toxicants amongst volatile compounds emitted during large-scale thermal degradation of poly(acrylonitrile-butadiene-styrene) plastic.
- Author
-
Shapi MM and Hesso A
- Subjects
- Air Pollutants, Occupational analysis, Gas Chromatography-Mass Spectrometry, Temperature, Acrylic Resins analysis, Butadienes analysis, Plastics analysis, Polystyrenes analysis
- Abstract
A number of compounds emitted during the thermal degradation of plastics are potentially toxic. This study was aimed at identifying the volatile compounds emitted during large-scale thermal degradation of poly(acrylonitrile-butadiene-styrene). About 5 g of the sample were degraded at between 25 and 470 degrees C in air and nitrogen in a device that can simulate temperature-programmed thermogravimetry. The volatiles were collected in dichloromethane using the solvent trap technique. Some of the 92 compounds identified by gas chromatography-mass spectrometry were found to have no hitherto documented toxicological profiles, even though they are potentially dangerous.
- Published
- 1991
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