Collin Hill, undergraduate majoring in Biology and Chemistry, presented his Honors Biology Thesis which focused on the very timely topic of virology. Collin summarizes his thesis:
“In this study, we examined three potentially mutagenic nucleoside analogs, N4-beta-hydrocytidine (NHC), Favipiravir, and Ribavirin using Primer ID with next-generation sequencing (NGS) on a panel of RNA viruses in cell culture, including MERS coronavirus (MERS-CoV), Zika virus (ZIKV), and La Crosse virus (LACV). We found that NHC exhibited antiviral and mutagenic effects in each of the three viruses, supporting that this nucleoside analog is a broad-spectrum antiviral that acts through lethal mutagenesis. Favipiravir and Ribavirin was found to exhibit moderate antiviral and mutagenic effects in LACV only. Additionally, using a MERS-CoV mouse model, we found that an NHC prodrug (EIDD-2801) also exhibited the same antiviral and mutagenic effects in vivo and also found that there was no significant findings of cytotoxicity or increases in transcriptional error rates. However, an additional study of cytotoxicity of each of the three nucleoside analogs in a cell culture of 8E5 cells found that NHC at high dosage concentrations can significantly increase the transcriptional error rate of the cells, indicating misincorporation of NHC by eukaryotic RNA polymerases. The findings of this study support that these nucleoside analogs could potentially be able to be used to treat a wide variety of RNA viral infections in humans, including newly emerged viruses that lack other forms of treatment.”