Conserved structural motif D as a target for viral attenuation and vaccine development. (A) Conservation of the motif D lysine in viral RdRps. (B) K359R PV exhibits a delayed growth phenotype. (C) K359R PV is attenuated. (D) K359R PV elicits a protective immune response. Adapted from S.A. Weeks, C.A. Lee, Y. Zhao, E.D. Smidansky, A. August, J.J. Arnold, C.E. Cameron, A polymerase mechanism-based strategy for viral attenuation and vaccine development, J. Biol. Chem. 287 (38) (2012) 31618–31622.