Faculty Advisor

Adams, David S.

Abstract

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.

Publisher

Worcester Polytechnic Institute

Date Accepted

April 2012

Major

Biology and Biotechnology

Project Type

Major Qualifying Project

Accessibility

Unrestricted

Advisor Department

Biology and Biotechnology

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