Details

Autor(en) / Beteiligte

• Ahmad, Shaban
• Singh, Akash Pratap
• Bano, Nagmi
• Raza, Khalid
• Singh, Janmejay
• Medigeshi, Guruprasad R.
• Pandey, Rajesh
• Gautam, Hemant K.

Titel

Integrative analysis discovers Imidurea as dual multitargeted inhibitor of CD69, CD40, SHP2, lysozyme, GATA3, cCBL, and S-cysteinase from SARS-CoV-2 and M. tuberculosis

Ist Teil von

• International journal of biological macromolecules, 2024-06, Vol.270 (Pt 2), p.132332-132332, Article 132332

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2024

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.