Ebolaviruses can cause severe haemorrhagic fever and was responsible for the 2013-2015 epidemic in West Africa, that resulted in over 11,000 deaths. Utilizing our fragments library, we employed saturation transfer difference nuclear magnetic resonance (STD NMR) spectroscopy to identify fragments that bound Filoviridae family members, Ebolavirus Zaire or Marburgvirus Lake Victoria nucleoprotein transcriptional cofactor VP30. Due to the adaptive tendencies of viral proteins, we identified fragments that bound one or both strains. To further interrogate the potential relationship of fragments with Ebola, additional STD NMR screening of Ebolavirus Zaire mutants was performed, determining the difference signal of select fragments with the active “unphosphorylated” and inactive “phosphorylated” mutants. A greater difference signal was observed with the active mutant which also included the Marburgvirus specific fragments. We believe that our findings and strategy lead towards a structure guided drug design path for more successful viral therapies in Ebola and can be applied to other pathogens.