دورية أكاديمية
Matrix metalloproteinase/Fas ligand (MMP/FasL) interaction dynamics in COVID-19: An in silico study and neuroimmune perspective
| العنوان: | Matrix metalloproteinase/Fas ligand (MMP/FasL) interaction dynamics in COVID-19: An in silico study and neuroimmune perspective |
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| المؤلفون: | Kiarash Saleki, Cena Aram, Parsa Alijanizadeh, Mohammad Hossein Khanmirzaei, Zahra Vaziri, Mohammad Ramzankhah, Abbas Azadmehr |
| المصدر: | Heliyon, Vol 10, Iss 10, Pp e30898- (2024) |
| بيانات النشر: | Elsevier, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Science (General) LCC:Social sciences (General) |
| مصطلحات موضوعية: | Matrix metalloproteinase, Fasa ligand (FasL), Hyperinflammation, COVID-19, Immunoinformatics, Science (General), Q1-390, Social sciences (General), H1-99 |
| الوصف: | Background: The initiator of cytokine storm in Coronavirus disease (COVID-19) is still unknown. We recently suggested a complex interaction of matrix metalloproteinases (MMPs), Fas ligand (FasL), and viral entry factors could be responsible for the cytokine outrage In COVID-19. We explored the molecular dynamics of FasL/MMP7-9 in COVID-19 conditions in silico and provide neuroimmune insights for future. Methods: We enrolled and analyzed a clinical cohort of COVID-19 patients, and recorded their blood Na + levels and temperature at admission. A blood-like molecular dynamics simulation (MDS) box was then built. Four conditions were studied; MMP7/FasL (healthy), MMP7/FasL (COVID-19), MMP9-FasL (healthy), and MMP9/FasL (COVID-19). MDS was performed by GROningen MAchine for Chemical Simulation (GROMACS). We analyzed bonds, short-range energies, and free binding energies to draw conclusions on the interaction of MMP7/MMP9 and FasL to gain insights into COVID-19 immunopathology. Genevestigator was used study RNA-seq/microarray expression data of MMPs in the cells of immune and nervous systems. Finally, epitopes of MMP/FasL complexes were identified as drug targets by machine learning (ML) tools. Results: MMP7-FasL (Healthy), MMP7-FasL (COVID-19), MMP9-FasL (Healthy), and MMP9-FasL (COVID-19) systems showed 0, 1, 4, and 2 salt bridges, indicating MMP9 had more salt bridges. Moreover, in both COVID-19 and normal conditions, the number of interacting residues and surface area was higher for MMP9 compared to MMP7 group. The COVID-19 MMP9-FasL group had more H-bonds compared to MMP7-FasL group (12 vs. 7). 15 epitopes for FasL-MMP9 and 10 epitopes for FasL-MMP7 were detected. Extended MD simulation for 100 ns confirmed stronger binding of MMP9 based on Molecular Mechanics Generalized Borne Surface analysis (MM-GBSA) and Coul and Leonard-Jones (LJ) short-range energies. Conclusions: MMP9 interacts stronger than MMP7 with FasL, however, both molecules maintained strong interaction through the MDS. We suggested epitopes for MMP-FasL complexes as valuable therapeutic targets in COVID-19. These data could be utilized in future immune drug and protein design and repurposing efforts. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2405-8440 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S2405844024069299; https://doaj.org/toc/2405-8440 |
| DOI: | 10.1016/j.heliyon.2024.e30898 |
| URL الوصول: | https://doaj.org/article/d3d87f1ecad0431d9e05b8f2116a3b32 |
| رقم الأكسشن: | edsdoj.3d87f1ecad0431d9e05b8f2116a3b32 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 24058440 |
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| DOI: | 10.1016/j.heliyon.2024.e30898 |