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In Vitro And In Vivo Characterization Of The Metallodrug Bold-100 As An Inhibitor Of Sars-Cov-2 Replication, Daniel S. Labach

Electronic Thesis and Dissertation Repository

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused extensive mortality and societal disruption. BOLD-100 is a novel anticancer therapeutic being considered to treat COVID-19. We hypothesized that BOLD-100 inhibits SARS-CoV-2 replication and progression of COVID-19. Using Western blotting, quantitative RT-PCR, and cell viability assays, we determined that BOLD-100 inhibits SARS-CoV-2 replication in vitro. RNA sequencing analysis demonstrated that BOLD-100 inhibits virus-induced transcriptional changes in infected cells. Intravenous BOLD-100 treatment of SARS-CoV-2-infected hamsters did not significantly alter body weight, lung viral load or pathological lesions. Finally, we showed that the antiviral activity of BOLD-100 …

Evaluation Of Therapeutics For An Enterovirus 71 Infection In An Ag129 Mouse Model, Christopher Peterson

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Discovered in 1969 in California, enterovirus 71 (EV-71) is a serious cause of disease in young children. It is one of the major causative agents of hand, food, and mouth disease (HFMD), and can produce neurological complications, such as meningitis, encephalitis, and an acute flaccid paralysis. For serious cases, the fatality rate can be up to 26%, almost exclusively in young children.

While the virus was initially discovered in the United States, it was soon detected in the Eastern hemisphere, causing outbreaks in Europe and Asia. The largest outbreak occurred in Taiwan in 2008, with approximately 490,000 cases and 128 …

Restriction Of Hiv-1 Replication By Unique Trim22 Isoforms., Clayton Hattlmann

Electronic Thesis and Dissertation Repository

Understanding how the immune system reacts to HIV infection and why normal antiviral defenses are insufficient to fight infection is a key step towards creating better therapies. Several interferon-induced proteins, such as the tripartite motif protein TRIM22, are capable of restricting HIV-1 replication; however single nucleotide polymorphisms (SNPs) can dramatically impact the actions of these proteins. While the trim22 gene contains numerous SNPs, no study has addressed how these may affect TRIM22 functions. Here we provide the first direct comparison of two TRIM22 unique isoforms. Through confocal microscopy we observed these isoforms exhibit different patterns of localization. In vitro studies …