Abstract: Viral agents are responsible for periodic epidemics (or pandemics) that result in significant morbidity and mortality often causing colossal economic impact. Although viral outbreaks can be limited/controlled by vaccination, education efforts and hygiene, there remains a need for ancillary treatment modalities. The current armamentarium of antiviral drugs is typically efficacious, but practically prone to diminished utility due to widespread use leading to viral recombination and resistance. Therefore, new methods of drug discovery are sought to identify novel antiviral compounds from previously unmined libraries. Because many medically important viruses utilize the lytic life cycle, drug discovery assays that measure host cell health can inversely report viral activity. For instance, the tetrazolium family of compounds (WST-1, XTT, MTT, and MTS) have been used to define viral infectivity by measuring changes in monolayer integrity. However, these assays are poorly suited for high throughput screening (HTS) due to poor sensitivity and/or multiple assay steps. We have developed a bioluminescent assay which measures cellular ATP. Because ATP is tightly regulated in cells, it serves as an excellent surrogate for host cell viability. Here we use four clinically significant viruses and four host cell lines to show that Viral ToxGlo™ can be utilized for determining the relative viral-burden in a sample for screening and characterizing antiviral compound potency during drug discovery.Summary: Viral agents are responsible for periodic epidemics (or pandemics) that result in significant morbidity and mortality often causing colossal economic impact.References:
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