Browsing by Author "Sahini, Mtabazi G."
Now showing 1 - 7 of 7
Results Per Page
Sort Options
Item Abrogating the nsp10–nsp16 switching mechanisms in SARS-CoV-2 by phytochemicals from Withania somnifera: a molecular dynamics study(Taylor & Francis, 2021) Vuai, Said A. H.; Onokaa, Isaac; Sahini, Mtabazi G.; Swai, Hulda S.; Shadrack, Daniel M.The search for therapeutic small molecules and vaccines for Covid-19 treatment is an urgent but evolving topic. The virus has claimed over 3,782,490 lives (as of 12 June 2021), with the figure expected to rise due to the high versatility of the SAR-CoV-2 variant. Therapeutic options based on SARS-CoV-2 inhibitor are essential. Withanolides have a long history in traditional medicines with versatile biological properties including antiviral activities. In this study, the inhibitory potential of withanolides from Withania somnifera (Ashwagandha) against SARS-CoV-2 non-structural protein 10 (nsp10) was investigated by employing atomistic in silico methods viz molecular docking, molecular dynamics and binding free energy calculations. Investigated Withania somnifera compounds demonstrated binding affinity to the nsp10 and in its complex form, that is, nsp10-nsp16 heterodimer. Two withanolides; withanoside IV and withanoside V isolated from the roots of Withania somnifera demonstrated strong inhibition with binding free energies of −29.5 and −29.1 kJ/mol, respectively. Molecular dynamics and binding free energy ascertained the stability of withanoside IV. Water molecules, although known to play an important role in mediating biological systems, herein, water was found to have a repulsive binding effect to some residues, suggesting that the binding of withanoside IV would require dewetting of the nsp10 or displacing the water to bulk solvents. Interestingly, residues in the nsp10 that are responsible for forming stable interaction at the nsp10–nsp16 were found to be strongly interacting with withanoside IV, hence weakening the nsp10–nsp16 interaction and recognition. Further in vitro and in vivo experiments are recommended to validate the anti-SARS-COV-2 potential of these phytochemicals.Item Abrogating the nsp10–nsp16 switching mechanisms in SARS-CoV-2 by phytochemicals from Withania somnifera: a molecular dynamics study(Taylor & Francis, 2021) Vuai, Said A. H.; Onoka, Isaac; Sahini, Mtabazi G.; Swai, Hulda S.; Shadrack, Daniel M.The search for therapeutic small molecules and vaccines for Covid-19 treatment is an urgent but evolving topic. The virus has claimed over 3,782,490 lives (as of 12 June 2021), with the figure expected to rise due to the high versatility of the SAR-CoV-2 variant. Therapeutic options based on SARS-CoV-2 inhibitor are essential. Withanolides have a long history in traditional medicines with versatile biological properties including antiviral activities. In this study, the inhibitory potential of withanolides from Withania somnifera (Ashwagandha) against SARS-CoV-2 non-structural protein 10 (nsp10) was investigated by employing atomistic in silico methods viz molecular docking, molecular dynamics and binding free energy calculations. Investigated Withania somnifera compounds demonstrated binding affinity to the nsp10 and in its complex form, that is, nsp10-nsp16 heterodimer. Two withanolides; withanoside IV and withanoside V isolated from the roots of Withania somnifera demonstrated strong inhibition with binding free energies of −29.5 and −29.1 kJ/mol, respectively. Molecular dynamics and binding free energy ascertained the stability of withanoside IV. Water molecules, although known to play an important role in mediating biological systems, herein, water was found to have a repulsive binding effect to some residues, suggesting that the binding of withanoside IV would require dewetting of the nsp10 or displacing the water to bulk solvents. Interestingly, residues in the nsp10 that are responsible for forming stable interaction at the nsp10–nsp16 were found to be strongly interacting with withanoside IV, hence weakening the nsp10–nsp16 interaction and recognition. Further in vitro and in vivo experiments are recommended to validate the anti-SARS-COV-2 potential of these phytochemicals.Item Cation inter-diffusion and formation of intermediate phases in CoO and La2NiO4+δ diffusion couples(Elsevier, 2022) Sahini, Mtabazi G.; Wiik, Kjell; Grande, TorCation interdiffusion between La2NiO4+δ (LN) and CoO diffusion couples was investigated by thermal annealing in ambient air at 1200 °C for 48 and 168 h, and analysis of the cross sections by scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS). Co diffusion into the LN layer was significant, while Ni diffusion into the CoO layer was minor. Formation of LaCoO3, LaCo0.5Ni0.5O3, and La3(Ni0.8Co0.2)2O7 were observed in the LN layer at increasing distance from the boundary.Item Cation–π interactions drive hydrophobic self-assembly and aggregation of niclosamide in water †(The Royal Society of Chemistry, 2021) Vuai, Said A. H.; Sahini, Mtabazi G.; Onoka, Isaac; Kiruri, Lucy W.; Shadrack, Daniel M.The beneficial medicinal effects of niclosamide have been reported to be hampered by poor aqueous solubility and so a higher concentration dosage is required. In this work, we have studied the aggregation properties of niclosamide in water by varying the number of monomers. We have employed all-atom classical molecular dynamics simulation in order to explore such properties. The equilibrium structure exists in an aggregated state with structural rearrangements of the stacking units. Niclosamide monomers tend to form clusters in an orderly manner and tend to aggregate in parallel and antiparallel orientations of the phenyl rings as the monomers are increased in number from 4 to 9. Upon increasing the size from 9 to 14, and from 49 to 150, a considerable dominance of the metastable parallel arrangement is observed, resulting in the formation of a closely packed cluster with hydrophobic contacts. The metastable conformation self-arranges to a T-shape before forming a stable planar antiparallel displaced conformation. The aggregated π–π parallel and cation–π antiparallel clusters in water exist in a β-conformer. We further observed that formation of a stable cluster aggregate entails the formation of an intermediate metastable cluster that disperses in solution forming a large stable cluster. We also discovered that movement of the water is faster in less aggregated clusters and as the cluster size increases, the mobility rate becomes much slower.Item Ethnomedicinal uses, phytochemistry and pharmacological study of Ocimum americanum L.: A review(Elsevier, 2023) Luanda, Amos; Ripanda, Asha; Sahini, Mtabazi G.; Makangara, John J.Background: Ocimum americanum L., commonly known as Hoary basil, is a wild aromatic shrub traditionally used to treat different ailments. Its leaves, flowers and aerial parts have been widely studied to evaluate its medicinal potential such as lowering blood pressure, treatment of microbial infections, malaria, cold, liver and eye problems. Purpose: This study aims to provide an in-depth review of ethnomedicinal uses, phytochemistry, and pharmacological activities of O. americanum, to evaluate its benefits, challenges and potential future prospects. Methods: All the information about O. americanum was collected from various platforms, including google scholar, PubMed, ScienceDirect, plants of the world online and Research4Life. The acceptance criteria of the collected information based on the PICOS model. The GRADE approach was used to analyze and evaluate the quality of the collected information. Results: This study showed that O. americanum has tremendous therapeutic potential to be integrated into mainstream medical practice to manage various medical conditions. The inconsistence of the phytoconstituents among the plant parts resulted in a significant variation of pharmacological activities. Plant originality, genetic variability and extraction techniques are among the factors contributing to the variation of phytoconstituents that are responsible for pharmacological activities. Conclusion: This study revealed that O. americanum is a potential medicinal plant for mitigating various medical conditions. However, future study should continue to focus on the bioactive compounds and their mechanisms of action. Additionally, the utilization of the O. americanum for the development of drugs as well as quality evaluation in clinical settings are highly recommended.Item Relaxed complex scheme and molecular dynamics simulation suggests small molecule inhibitor of human TMPRSS2 for combating COVID-19(Taylor & Francis, 2021) Vuai, Said A. H.; Ogedjo, Marcelina M.; Isaac, Onoka; Sahini, Mtabazi G.; Swai, Hulda S.; Shadrack, Daniel M.As the coronavirus disease 19 (COVID-19) pandemic continues to pose a health and economic crisis worldwide, the quest for drugs and/or vaccines against the virus continues. The human transmembrane protease serine 2 (TMPRSS2) has attracted attention as a target for drug discovery, as inhibition of its catalytic reaction would result in the inactivation of the proteolytic cleavage of the SARS-CoV-2 S protein. As a result, the inactivation prevents viral cell entry to the host’s cell. In this work, we screened and identified two potent molecules that interact and inhibit the catalytic reaction by using computational approaches. Two docking screening experiments were performed utilizing the crystal structure and holo ensemble structure obtained from molecular dynamics in bound form. There is enhancement and sensitivity of docking results to the holo ensemble as compared to the crystal structure. Compound 1 demonstrated a similar inhibition value to nafamostat by interacting with catalytic triad residues His296 and Ser441, thereby disrupting the already established hydrogen bond interaction. The stability of the ligand–TMPRSS2 complexes was studied by molecular dynamics simulation, and the binding energy was re-scored by using molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) binding free energy. The obtained compounds may serve as an initial point toward the discovery of potent TMPRSS2 inhibitors upon further in vivo validation.Item Towards attaining SDG 6: The opportunities available for capacitive deionization technology to provide clean water to the African population(Elsevier, 2022) Sufiani, Omari; Sahini, Mtabazi G.; Elisadiki, JoyceThe unavailability of clean water caused by population growth, increased industrial activities, and global climate change is a major challenge in many communities. A number of desalination technologies including distillation, reverse osmosis and electrodialysis, have been used to supplement the available water resources. However, these technologies are energy intensive and demand a significant financial commitment. Capacitive deionization (CDI) is an emerging desalination technology which is promising to provide water at a reasonable cost, especially in societies with limited incomes such as those in Africa. The opportunities for CDI to provide clean water to the African population are discussed in this paper. These opportunities include electrosorption at low potential, low energy consumption, large quantities of agricultural wastes for the production of electrode materials, high sunshine irradiation throughout the year, suitability for disinfection and defluoridation and its applications in the removal of heavy metals and emerging pollutants. Due to the existence of numerous enabling conditions, the analysis from this paper demonstrates that CDI can be a dependable method to provide clean water in Africa.