Browsing by Author "Fouad, Mostafa A."

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    Dereplication Analysis and Antitrypanosomal Potential of the Red Sea Sponge Amphimedon sp. Supported by Molecular Modelling
    (Springer, 2020-03) Hisham Shady, Nourhan; Elfakharany, Zeinab; Salem, M. Alaraby; Ahmed, Safwat; Fouad, Mostafa A.; Salah Kamel, Mohamed; Krischke, Markus; Mueller, Martin J.; Abdelmohsen, Usama Ramadan
    The present investigation was oriented to the discovery of chemical compounds from the Red Sea sponge Amphimedon sp., as a source of active agents against Trypanosoma brucei, the causal agent of human sleeping sickness. Dereplication analysis of the active fraction from Amphimedon sp. using liquid chromatography coupled with high-resolution mass spectrometry revealed the chemical richness of this sponge with diverse alkaloidal classes such as purine, manzamine, bis-piperidine, and pyridine. Activity-guided fractionation of the total extract showed the antitrypanosomal activity concentrated in the ethyl acetate fraction (IC50 = 3.8 μg/ml). In silico modelling was carried out on the dereplicated compounds to provide an insight into their antitrypanosomal mechanism of action with docking study on eight trypanosomal proteins. Molecular dynamics was run for the complex of zamamidine D and ornithine decarboxylase, which illustrated that zamamidine D has the highest affinity to the ornithine decarboxylase enzyme. These results highlight the valuable chemical profile of Amphimedon sp., as a lead source for antitrypanosomal natural products.
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    Multitarget in silico studies of Ocimum menthiifolium, family Lamiaceae against SARS-CoV-2 supported by molecular dynamics simulation
    (Taylor and Francis, 2020-12) Zahran, Eman Maher; Fouad, Mostafa A.; Abdelmohsen, Usama Ramadan; Kamel, Mohamed S; Khalil, Hany Ezzat; Desoukey, Samar Yehia; Salem, Mohammad Alaraby
    The novel strain of human coronavirus, emerged in December 2019, which has been designated as SARS-CoV-2, causes a severe acute respiratory syndrome. Since then, it has arisen as a serious threat to the world public health. Since no approved vaccines or drugs has been found to efficiently stop the virulent spread of the virus, progressive inquiries targeting these viruses are urgently needed, especially those from plant sources. Metabolic profiling using LC-HR-ESI-MS of the butanol extract of Ocimum menthiifolium (Lamiaceae) aerial parts yielded 10 compounds including flavonoids, iridoids and phenolics. As it has been previously reported that some flavonoids can be used as anti-SARS drugs by targeting SARS-CoV-1 3CLpro, we chose to examine 14 flavonoids (detected by metabolomics and other compounds isolated via several chromatographic techniques). We investigated their potential binding interactions with the 4 main SARS-CoV-2 targets: Mpro, nsp16/nsp10 complex, ACE2-PD and RBD-S-protein via molecular docking. Docking results indicated that the nsp16/nsp10 complex has the best binding affinities where the strongest binding was detected with apigenin-7-O-rutinoside, prunin and acaciin with 9.4, 9.3 and 9.3kcal/mol binding energy, respectively, compared to the control (SAM) with 8.2kcal/mol. Furthermore, the stability of these complexes was studied using molecular dynamics of 150ns, which were then compared to their complexes in the other three targets. MM-PBSA calculations suggested the high stability of acaciin-nsp16 complex with binding energy of 110kJ/mol. This study sheds light on the structure-based design of natural flavonoids as antiSARS-CoV-2 drugs targeting the nsp16/10 complex. Abbreviations: ACE2-PD: Angiotensin converting enzyme 2 protease domain; ARDS: Acute respiratory distress syndrome; COVID-19: Corona virus disease; Mpro: Main protease; MD: Molecular dynamics; PDB: Protein data bank; RBD-S: Receptor binding domain; RMSD: Root mean square deviation; SAM: Sadenosylmethionine; SARS: Severe acute respiratory syndrome