Richard Plemper, PhD
Center for Inflammation, Immunity & Infection
Georgia State University
Paramyxoviruses, enveloped, negative strand RNA viruses, cause significant morbidity and mortality worldwide. Members of this family include measles virus (MV), respiratory syncytial virus (RSV), human parainfluenza viruses (hPIV), and the recently emerged and highly pathogenic Nipah and Hendra viruses. It is the ultimate goal of my team to better understand paramyxovirus entry and genome replication, and apply this knowledge to the development of novel strategies to intervene with paramyxovirus infection.
Investigating the molecular mechanism by which the viral fusion protein mediates membrane merger has led us to the structure-based development of a novel class of small-molecule MV entry inhibitors. Complementing these drug design efforts, we have developed an assay system for the automated discovery of entry and polymerase inhibitors. Implementation of this assay in a pilot screen has resulted in the discovery of a first in class non-nucleoside inhibitor of the viral RNA-dependent polymerase complex with high therapeutic potential.
Current research focuses on a detailed understanding of the molecular mechanism of inhibition and, in an interdisciplinary collaboration with the Department of Chemistry, the development of both inhibitor classes to therapeutic leads. In addition to their therapeutic potential, we employ in parallel both inhibitor classes as innovative research tools through investigating patterns of viral escape from inhibition. Compiling the results of these approaches will advance our basic understanding of viral entry and replication, and ultimately allow the rational development of further optimized, highly potent antivirals.