Project Type MQP Submission date 2012-04-26 Author Katelyn Diane Comeau, BIO URN E-project-042612-131319 Sponsor Microbiotix, Inc Title CHARACTERIZATION OF NOVEL NUCLEOSIDE ANALOG DRUGS AGAINST HSV-1 INFECTION Advisor Adams, David S., BB Availability unrestricted
Infection with Herpes Simplex Virus-1 (HSV-1) is common in humans, and can lead to severe symptoms if drug resistance occurs. This project aimed to select a novel nucleoside analog showing potential as an HSV-1 antiviral therapy, and to begin to characterize its mechanism of action. Using plaque reduction and MTS assays, compound MBX 2168 was identified as a potential candidate with strong antiviral activity and low toxicity. Mutational studies of 3 viral kinases and kinetic studies of human 2-deoxyguanosine kinase (dGK) suggest that MBX 2168 is not initially phosphorylated by those viral kinases and is not phosphorylated by human dGK. Sequence analysis and molecular modeling of an HSV-1 strain resistant to MBX 2168 suggest that the drug works by inhibiting HSV-1 DNA synthesis.
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