Towards The Rational Design of Epstein Barr Nuclear Antigen 1 Inhibitors 

- by Dr. Xavier Chee Wezen

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Abstract:

Nasopharyngeal cancer (NPC) is a type of malignant tumour that is prevalent in Southern China and South East Asia. The latent infection of the Epstein Bar Virus (EBV) is a known etiological factor that leads to the development of NPC. Currently, the only known protein necessary for the maintenance of EBV episome in infected cells is the EBV Nuclear Antigen 1 (EBNA1) protein. In our work, we are interested to discover new small molecular drugs against EBNA1. Using supervised Molecular Dynamics simulation, we simulated the binding of VK-1248 (a known EBNA1 inhibitor) onto EBNA1. Combining the insights from our MD simulation and machine learning, we predicted and purchased potential EBNA1 inhibitors for experimental testing. Preliminary screening using these compounds showed differential effects against EBV-positive and EBV-negative NPC cells. Our current work continues on with gene expression studies to ascertain these compounds as bona fide EBNA1 inhibitors.