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Identification of a compound series by high throughput screening capable of reversing the antiviral effect of Ribavirin in tissue culture

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dc.contributor.advisor Dreher, Theo
dc.creator Gallion, Jonathan
dc.date.accessioned 2012-09-04T18:18:04Z
dc.date.available 2012-09-04T18:18:04Z
dc.date.issued 2012-06-14
dc.identifier.uri http://hdl.handle.net/1957/33173
dc.description.abstract A compound series capable of reversing the antiviral effect of Ribavirin (RBV) against H1N1 was identified from a high throughput screen designed to discover compounds capable of increasing the fidelity of the RNA-dependent RNA polymerase (RDRP) n ribovirus quasispecies. Two lead compounds, RIC-1 (EC50 of 78.4 nM) and RIC-2 (EC50 of 217 nM), returned viral growth to control levels by completely inhibiting the antiviral activity of RBV. Both compounds demonstrated a loss of activity when incubated at 37°C in media only, losing functionality within 3 hours. Incubation of RIC-1 or RIC-2 with cells for only 2.5 minutes, however, was able to maintain viral growth by inhibiting RBV for the full 72 hour growth period. Subsequent testing showed the RIC series was not effective against a second mutagen, 5-fluorouracil, and RIC-2 did not prevent or slow the development of antiviral resistance when viral populations were grown in the presence of Zanamivir. Furthermore, RIC-1 was ineffective in alleviating inhibition of the inosine 5’-monophosphate dehydrogenase (IMPDH) pathway by the inhibitor mycophenolic acid (MPA). Anti-RBV activity was relieved by increasing the concentration of RBV, suggesting the RIC series acts to competitively inhibit RBV. The mechanism of action associated with the RIC compound series is still unclear; however, it appears to act independent of the intended function of RDRP fidelity modification. en_US
dc.language.iso en_US en_US
dc.subject Ribavirin (RBV) en_US
dc.subject RDRP Fidelity en_US
dc.subject Influenza H1N1 en_US
dc.subject Equilibrative Nucleoside Transporter (ENT-1) en_US
dc.subject Inosine monophosphate dehydrogenase (IMPDH) en_US
dc.title Identification of a compound series by high throughput screening capable of reversing the antiviral effect of Ribavirin in tissue culture en_US
dc.type Thesis/Dissertation en_US
dc.degree.name Honors Bachelor of Science (HBS) en_US
dc.degree.level Bachelor's en_US
dc.degree.discipline Honors College en_US
dc.degree.grantor Oregon State University en_US

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  • Honors College Theses
    The University Honors College requires a senior thesis for receipt of OSU’s most prestigious degree, the Honors Baccalaureate.

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