Browsing by Author "Onoka, Isaac"

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    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.
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    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.
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    Luteolin: a blocker of SARS-CoV-2 cell entry based on relaxed complex scheme, molecular dynamics simulation, and metadynamics
    (Springer, 2021) Shadrack, Daniel M.; Deogratias, Geradius; Kiruri, Lucy W.; Onoka, Isaac; Vianne, John-Mary; Swai, Hulda; Nyandoro, Stephen S.
    Natural products have served human life as medications for centuries. During the outbreak of COVID-19, a number of naturally derived compounds and extracts have been tested or used as potential remedies against COVID-19. Tetradenia riparia extract is one of the plant extracts that have been deployed and claimed to manage and control COVID-19 by some communities in Tanzania and other African countries. The active compounds isolated from T. riparia are known to possess various biological properties including antimalarial and antiviral. However, the underlying mechanism of the active compounds against SARS-CoV-2 remains unknown. Results in the present work have been interpreted from the view point of computational methods including molecular dynamics, free energy methods, and metadynamics to establish the related mechanism of action. Among the constituents of T. riparia studied, luteolin inhibited viral cell entry and was thermodynamically stable. The title compound exhibit residence time and unbinding kinetics of 68.86 ms and 0.014 /ms, respectively. The findings suggest that luteolin could be potent blocker of SARS-CoV-2 cell entry. The study shades lights towards identification of bioactive constituents from T. riparia against COVID-19, and thus bioassay can be carried out to further validate such observations.
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    A review of the newly identified impurity profiles in methamphetamine seizures
    (Elsevier, 2020) Onoka, Isaac; Banyika, Andrew Toyi; Banerjee, Protibha Nath; Makangara, John J.; Dujourdy, Laurence
    Forensic intelligence of synthetic illicit drugs suffers a problem of continuous introduction of new synthetic methods, modification of the existing routes of manufacture, and adulterations practiced by criminal networks. Impurity profiling has been indispensable in methamphetamine intelligence based on precursors, synthetic routes, and chemical modifications during trafficking. Law enforcement authorities maintain the credibility and integrity of intelligence information through constant monitoring of the chemical signatures in the illicit drug market. Changes in the synthetic pattern result in new impurity profiles that are important in keeping valuable intelligence information on clandestine laboratories, new synthetic routes, trafficking patterns, and geographical sources of illicit Methamphetamine. This review presents a critical analysis of the methamphetamine impurity profiles and more specifically, profiling based on impurity profiles from Leuckart, Reductive amination, Moscow, Emde, Nagai, Birch, Moscow route; a recent nitrostyrene route and stable isotope signatures. It also highlights the discrimination of ephedrine from pseudoephedrine sources and the emerging methamphetamine profiling based on stable isotopes.
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    Theoretical studies of electronic and optical properties for some new azo disperse dyes for dye-sensitized solar cells by using TD and TD DFT method
    (East African Nature and Science Organization, 2018) Onoka, Isaac; Babu, Numbury Surendra; Makangara, John J.
    The ground states geometries, absorption wavelengths, oscillation strengths of new azo disperse dyes such as 3-aminopyrazoleazo -4- thiol-2,3,5-thiadiazole (D1),3-amino-4-methylpyrazoleazo-4-thiol-2,3, 5-thiadiazol (D2),2, 4-dihydroxybenzeneazo-4-thiol 1-2, 3,5- thiadiazole (D3),4-amino-3-benzonitrileazo-4-thiol-2,3,5-thiadiazole (D4), 2-hydroxylnaphtholazo-4-thiol-2,3,5-thiadiazole (D5) and 2-amino-5-ethylcarbazoleazo-4-thiol-2,3,5-Thiadiazole (D6) have been optimized by using density functional theory (DFT) at B3LYP level of theory with 6-31G(d) basis set. The excitation energies have been computed by using time dependent density functional theory (TDDFT). The study of structural, electronic and optical properties for these dyes could help to design more efficient functional photovoltaic organic materials. The electron injection (ΔGinject), electron coupling constants (|VRP|) and light harvesting efficiencies (LHE) of studied dyes and have been discussed with esteem to DSSCs. This theoretical designing will the pave way for experimentalists to synthesize the efficient sensitizers for solar cells