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Int J Biol Macromol ; 270(Pt 2): 132332, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38768914

RESUMO

Two of the deadliest infectious diseases, COVID-19 and tuberculosis (TB), have combined to establish a worldwide pandemic, wreaking havoc on economies and claiming countless lives. The optimised, multitargeted medications may diminish resistance and counter them together. Based on computational expression studies, 183 genes were co-expressed in COVID-19 and TB blood samples. We used the multisampling screening algorithms on the top ten co-expressed genes (CD40, SHP2, Lysozyme, GATA3, cCBL, SIVmac239 Nef, CD69, S-adenosylhomocysteinase, Chemokine Receptor-7, and Membrane Protein). Imidurea is a multitargeted inhibitor for COVID-19 and TB, as confirmed by extensive screening and post-filtering utilising MM\GBSA algorithms. Imidurea has shown docking and MM\GBSA scores of -8.21 to -4.75 Kcal/mol and -64.16 to -29.38 Kcal/mol, respectively. The DFT, pharmacokinetics, and interaction patterns suggest that Imidurea may be a drug candidate, and all ten complexes were tested for stability and bond strength using 100 ns for all MD atoms. The modelling findings showed the complex's repurposing potential, with a cumulative deviation and fluctuation of <2 Å and significant intermolecular interaction, which validated the possibilities. Finally, an inhibition test was performed to confirm our in-silico findings on SARS-CoV-2 Delta variant infection, which was suppressed by adding imidurea to Vero E6 cells after infection.


Assuntos
Tratamento Farmacológico da COVID-19 , COVID-19 , Simulação de Acoplamento Molecular , Mycobacterium tuberculosis , SARS-CoV-2 , SARS-CoV-2/efeitos dos fármacos , Humanos , COVID-19/virologia , Mycobacterium tuberculosis/enzimologia , Mycobacterium tuberculosis/efeitos dos fármacos , Simulação de Dinâmica Molecular , Muramidase/química , Muramidase/metabolismo , Antivirais/farmacologia , Antivirais/química , Ureia/farmacologia , Ureia/química , Antígenos de Diferenciação de Linfócitos T/metabolismo
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