Role of dynein and kinesin in viral proliferation & dynein inhibitors

Tati Padou, Martinet-Sayi’Mone (2021) Role of dynein and kinesin in viral proliferation & dynein inhibitors. Masters thesis, Memorial University of Newfoundland.

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Abstract

Dynein and kinesin are motor proteins involved in the retrograde and anterograde, respectively, transport of cargoes, including viral genomes following infection. Current literature reveals that both proteins play critical roles in ensuring successful viral proliferation. The literature also shows that the motor proteins are involved in the immunological response of host cells. Small-molecule inhibitors of kinesin and dynein inform of the function of the proteins during viral proliferation and immunological response. The investigation of the binding profile of small-molecule inhibitors of dynein, namely, ciliobrevin and analogues as well as dynapyrazole A and B, and the protonated forms of the lead compounds at the AAA1 binding site of dynein revealed the identity of the residues interacting with the inhibitors. This research project also analyzed the effect of isomerization of ciliobrevin on its binding profile, the impact of protonation of lead compounds on the binding affinity of the inhibitors, and the intramolecular interactions in dynein. The results suggest a potential residue in the AAA1 subunit of cytoplasmic dynein 1 that could be involved in the ‘glutamate switch’ mechanism, which according to the literature, has not been observed in dynein 1.

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