Dr. Pei-Wong Shi

When researcher Pei-Wong Shi completed his Ph.D. research on west Nile virus (WNV) a decade ago and headed off for a post-doc at Yale, he had no idea his work would hold any practical public health application.That changed quickly when WNV outbreaks began occurring regularly in New York State.Today, as a research scientist at the prestigious Wadsworth Center of the New York State Health Department (Albany, NY), Dr. Shi directs NIH-funded programs on the molecular biology of WNV and discovery of new drugs against the viral, mosquito-borne disease.

Shi and co-workers use CBAs to learn how wild-type and mutated WNV attaches to and enters cells.Since they know WNV's genetic sequence (it's an RNA virus), they can create artificial virus analogs by point nucleotide substitutions.Shi also incorporates genes for green fluorescent protein (GFP) or the luciferase enzyme into the genome, providing rapid, light-based assays for infectivity and virulence.

"This is a great system for drug discovery," says Dr. Shi, "because we can rapidly screen compounds exhibiting antiviral activity simply by measuring the amount of light given off after treatment of infected cells."After incubation with the experimental drug, Shi lyses the cell and interrogates the GFP or luciferase activity, which is proportional to virus replication.Shi has developed the assay in a semi-automated microwell plate format.

At one time, researchers interested in antiviral drug discovery needed to perform complex cell infectivity assays to determine the extent to which treatment inhibited viral replication."Using the older technology you would be lucky to test 20 compounds per day," Shi notes."Using our method, we can now investigate thousands of compounds per week."

Shi has attracted attention from other academic groups as well as the pharmaceutical industry, with which he collaborates on antiviral drug discovery.