Date of Award
Senior Honors Thesis
College or School
Molecular, Cellular, & Biomedical Sciences
Program or Major
Biochemistry, Molecular and Cellular Biology
Bachelor of Science
The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus disease 19 (COVID-19) pandemic has claimed the lives of roughly 6.2 million people worldwide as of May 2022. The virus’s main protease (Mpro ) has been identified as an attractive drug target due to the critical role it plays in the viral life cycle. The roughly 34 kDa Mpro cleaves functional viral polypeptides out of two long polyproteins at conserved cut sites, allowing them to fulfill their role in processes like transcription and replication. Here, we have studied the enzymatic activity and inhibition of Mpro and tested known (carmofur, ebselen, and tideglusib) and novel (CCG-50014, and CCG-203769) inhibitors using fluorescence spectroscopy. We report both the catalytic efficiency of Mpro (Kcat / KM = 27,900 M-1 s-1 M-1 s-1) and the IC50 values measured for tideglusib and ebselen (1.39 ± 0.2 µM and 0.40 ± 0.05 µM respectively) to be comparable to values published by Jin et al. . We also report that the novel CCG-50014 has comparable IC50 value (1.39 ± 0.22 µM) to known inhibitors of this enzyme.
Pascetta, Valerie Giovina, "Investigating the Main Protease (MPro) of SARS-CoV-2 as a Potential Drug Target" (2022). Honors Theses and Capstones. 621.