Kate is a rising junior studying Biochemistry at Vassar College. There Kate studies the structure and character of plasmid protein orf-90 under the mentorship of Dr. Krystle McLaughlin. The McLaughlin lab investigates the role of plasmid proteins in conferring antibiotic resistance. As an AMGEN Scholar at UCLA, Kate is working in Dr. Varghese John’s lab. Her project examines compounds that inhibit PLpro, a main protease integral to SARS-CoV-2 replication. Protease inhibitors could be a crucial protective agent against SARS-CoV-2, as they could be administered to infected individuals. By diminishing viral replication, the protease inhibitors diminish the prevalence of severe SARS-CoV-2 symptoms, long term SARS-CoV-2 symptoms, and hospitalizations. The John lab has identified two PLPro inhibitors: DDL-701 and DDL-715. Kate will measure the PLpro IC50 of these compounds to elucidate the proper dose. Subsequently, Kate will determine whether new chemical entities inhibit PLpro in a PLpro activity assay. These compounds will be derived from successful SARS-CoV-2 protease inhibitors, such as Paxlovid TM, DDL-701, and DDL-715. Employing Paxlovid TM with the most potent PLpro inhibitors may amplify the inhibition of viral replication. Kate will then examine the Phase 1 metabolism of DDL-701, DDL-715, and any other identified inhibitors. The results will help elucidate how the protease inhibitors are metabolized and the rate of this metabolism. Kate would like to thank Dr. Varghese John and Jesus Campagna for their invaluable support, as well as the Amgen Foundation for this opportunity.