Approach to Research

Antiviral Drug Design and Discovery, Part 2


Viruses require host cells for replication and, in turn, survival.  In this process, the invading virus commandeers the host cell's metabolic "pantry" for most of its essential replicative steps.  While depending extensively on the host cell for survival, viruses do generate a sizable number of enzymes and proteins specific to their own development (rather than depending exclusively on those of the host cell).  This latter unique characteristic forms the basis for selective drug design to affect viral replication.  Of particular interest to the Schneller group is the processing of messenger RNA (mRNA), which is the link between viral genetic information and viral progeny formation.


S-Adenosyl-L-methionine (AdoMet)-dependent transmethylations play an important role in regulating various biochemical and physiological processes.  One such process that is the focus of the Schneller laboratory is the formation of the methylated capped 5'-terminus of eukaryotic and viral mRNA.   These unique structures consist of (1) an N-7 methylguanosine residue linked at the 5'-hydroxyl group by a triphosphate to the 5'-end of the mRNA strand and (ii) a methyl substituent on the 2'-hydroxyl of the penultimate nucleotide.  Such methylations, which are catalyzed by N-7 methyltransferases and nucleoside 2'-methyltransferases that use AdoMet as the co-factor, are necessary for a fully functional mRNA. 

The research currently underway deals with antiviral drug design and discovery with focus on inhibition of terminal viral mRNA methylation.