Antiviral Drug Development

The Schneller research group:
Standing (left to right): Dean Schneller, Anatu Roy, Guoxia Zhao, Mingzhu He, Tanya Shulyak, Jian Zhou, Wei Ye, Cliff Yin
On top (left to right): Akin Akdag, Chong Liu, Weikuan Li, Tesfaye Serbessa

Rarely a month goes by that the medical community isn't reporting the appearance of a new viral threat to the well being of a local population with the likelihood that people and/or insect or animal vectors will spread this infection to other locales. Placing this in a historical perspective shows that mankind has had to coexist with, and combat, infectious agents for centuries. However recent circumstances have brought a more prevalent distribution of such agents: social globalization, increased microbial mutation rate, environmental alteration caused by urbanization, famine and poverty that accompany increasing populations, interspecies crossover of infectious diseases, immunomodulation in individuals, threat of bioterrorism, etc.

The research underway in the Schneller laboratory at Auburn University is focused on seeking drugs for the viruses in the emerging disease category for which no suitable therapy (including vaccination) exists.

Evolving from Dean Schneller's investigations seeking agents for treating human cytomegalovirus, it became apparent that a potentially fruitful approach to antiviral drug design was to inhibit the synthesis of viral proteins and enzymes that are necessary for replication. Dean Schneller's most recent research with smallpox has shown promising results in this direction.

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 sizeable 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.

Before being completely functional, mRNA must be enzymatically modified by methylation. The enzymes responsible for this are mRNA guanine 7-methyltransferase and mRNA 2'-O-nucleoside methyltransferase. Viral expression of these enzymes is known and their inhibition is being pursued in the Schneller research group.