Sophia
Brunkow
Sponsor: Stefan Rothenburg, M.D.,Ph.D. MED: Medical Microbiology&imm High throughput metagenomic sequencing is a powerful tool that can detect pathogenic DNA in tissue samples. Recently, an obscure poxvirus called BeAn 58058 (BAV), which was isolated from a sentinel rodent in Brazil one time in 1963, has been reported by metagenomic analyses of various of primate tissues. We conducted a systematic literature search and identified nine studies reporting reads for BAV. Proposed explanations for its's detection included true subclinical infections, contamination, integration of an ancient poxvirus into the host genome, and remnants of the smallpox vaccine. We can refute each of the above explanations with high confidence and have identified a primate short interspersed nuclear element (SINE) belonging to the Alu family in the genome of BAV, which we hypothesize to be linked to its misidentification in these studies. To identify if this was an isolated event, we performed a comprehensive database analysis of SINEs in viral genomes and detected numerous integrated host elements in both DNA and RNA viruses. Our findings highlight the necessity of using carefully curated databases and follow up analysis when employing metagenomics to detect viral infection, and identify SINEs as a source of genomic variation and innovation in viruses. Modeling Simultaneous Binding of Drugs and Sex-Steroid Hormones to the hERG Channel to Predict Sex-Specific Arrhythmia Risk
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Sophia Brunkow
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Voltage-gated ion channel proteins are essential in heart rhythm generation. The hERG potassium channel, KV11.1, is responsible for cardiac repolarization, and its blockade by a diverse set of small molecules may lead to prolonged ECG QT intervals and arrhythmias. Additionally, the female sex is known to be an independent risk factor for drug-induced cardiac arrhythmia, and several studies have shown sex hormone interactions with the hERG channel to be a possible direct cause of this risk. We performed AutoDock4 molecular docking with sixty-nine drugs classified by CredibleMeds as QT-prolonging to the hERG channel simultaneously with nine sex-steroid hormones. The binding cooperativity of drugs and female sex hormones in the channel pore is dependent upon their interactions with aromatic hERG channel residues. An analysis of these results shows a consistent pattern of drug-channel interactions which could be crucial to the mechanism of the sex-dependent drug-induced arrhythmia risk. We used all-atom molecular dynamics simulations followed by end-point binding free energy calculations with MM/ PBSA energy calculations to provide potentially more accurate energy estimates and confirm our molecular docking findings. These results will be used to accurately predict sex-dependent arrhythmia risks for multiple hERG blocking drugs. Infectious Disease Critical Values Requiring Urgent Clinician Notification in United States Hospitals Emily Buck
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UC Davis / MED: Pharmacology / 2026
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Sophia Brunkow