Investigating the Main Protease (MPro) of SARS-CoV-2 as a Potential Drug Target

Author

Valerie Giovina Pascetta, University of New HampshireFollow

Date of Award

Spring 2022

Project Type

Senior Honors Thesis

College or School

COLSA

Department

Molecular, Cellular, & Biomedical Sciences

Program or Major

Biochemistry, Molecular and Cellular Biology

Degree Name

Bachelor of Science

First Advisor

Krisztina Varga

Abstract

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 (M^pro ) has been identified as an attractive drug target due to the critical role it plays in the viral life cycle. The roughly 34 kDa M^pro 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 M^pro 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 M^pro (K_cat / K_M = 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. [13]. We also report that the novel CCG-50014 has comparable IC₅₀ value (1.39 ± 0.22 µM) to known inhibitors of this enzyme.

Recommended Citation

Pascetta, Valerie Giovina, "Investigating the Main Protease (MPro) of SARS-CoV-2 as a Potential Drug Target" (2022). Honors Theses and Capstones. 621.
https://scholars.unh.edu/honors/621