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Computatational Analysis of the Interaction between fibrinogen and COVID-19 spike protein
keywords COVID-19, DOCKING, FIBRINOGEN, HOMOLOGY MODELLING, IVERMECTIN, SPIKE PROTEIN
Reference persons JACEK ADAM TUSZYNSKI
External reference persons Alessandro Santin, Yale University, USA
Maral Aminpour, University of Alberta, Canada
Research Groups 28- biomedica
Thesis type COMPUTATIONAL
Description A recent publication indicated that Spike may bind directly to fibrinogen resulting in an induction of structurally abnormal blood clots with heightened proinflammatory activity. This is intriguing since it may provide an additional explanation for the development of micro-clotting in both acute Covid, Long Covid and in particular fully vaccinated individuals after received multiple shots using a pathogenic mechanism different from direct endothelial damage. We also now know that persistent production of Spike has now been demonstrated in human plasma and tissue cells for weeks during the acute infection and now for months/years in Long Covid. Importantly, the fibrotic (ie, fibrin Amyloid) clots causing thousands of deaths these days are notorious for being difficult to treat since they are highly resistant to fibrinolysis. Importantly, IVM may also have a beneficial effect both in acute infection, long covid as well as vaccinated patients since binding to the Spike protein may also potentially interfere with the binding to fibrinogen blocking/decreasing micro-clotting formation in individuals chronically producing spike protein. The crystal structure of spike is knowns. Fibrinogen structure is known for bovine and chicken but not human. However, we can create a human fibrinogen structure computationally using homology modeling. This would be the first step in the project. The second would be to dock spike protein to fibrinogen and evaluate the binding mode and strength of their interaction. Finally, using blind docking we will obtain the most probably interaction sites of ivermectin on fibrinogen. This will enable us to assess the correctness of the above hypothesis.
Required skills computational modeling of proteins and ligands, docking, homology modeling and molecular dynamics
Notes This project will be performed in collaboration with researchers in Canada and the US. The student may perform the computational work in Italy or in Canada.
Deadline 01/03/2024
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