Raymond F. Schinazi, PhD, DSc
Frances Winship Walters Professor
Laboratory of Biochemical Pharmacology
Senior Research Career Scientist
Scientific Working Group on Viral Eradication, Emory University Center for AIDS Research
The LOBP has established standardized protocols to evaluate novel compounds for their antiviral potency for a variety of human viruses and toxicity profiles using a panel of target cells. In addition, we also assay for selection of drug-resistance.
Selection of HIV-1 drug resistant viruses in PBM cells: Selection of drug resistant HIV will be carried out using established method (Schinazi et al 1993). The same protocol is used for selecting other viruses.
Characterization of drug-resistant viruses: After selecting resistant viruses, their phenotypes and genotypes will be characterized in detail. Phenotypic studies will include cross-resistance to structurally-related and unrelated compounds. In general, a statistically significant ≥ 5-fold increased EC50 compared to wild-type will be indicative of isolation of resistant virus. Direct sequencing of the PCR product will quickly identify the dominant mutations in the resistant virus population, whereas sequencing of individual plasmid clones or ultra deep sequencing can identify additional codon changes associated with resistance.
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