Molecular and Cellular Biosciences
College of Science & Mathematics
Nathaniel V. Nucci Ph.D.
Committee Member 1
Benjamin Carone Ph.D.
Committee Member 2
Yong Chen Ph.D.
Antiviral agents; Computer simulation
Bioinformatics | Medicine and Health Sciences
The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2020 has impacted daily life globally for over a year. While multiple vaccines have been authorized for emergency use and one oral medication has entered clinical trials, we are still seeking antiviral drugs for a long-term treatment for SARS-CoV-2 as well as other coronaviruses. Computational drug screenings of two SARS-CoV-2 protein target candidates are presented in this thesis: the nidoviral RNA uridylate-specific endoribonuclease (Nsp15) and the main protease (Mpro) of SARS-CoV-2. Nonstructural proteins of coronaviruses were selected as targets as they are more conserved across coronavirus strains than structural proteins. High throughput virtual screening of small molecule libraries including DrugBank and ZINC 15 resulted in several promising compounds for each of these targets. Molecular dynamics simulation allowed us to predict the binding energies for these compounds using molecular mechanics with generalized born surface area solvation calculations (MM-GBSA). Four top compounds were discovered for Nsp15 and eight compounds for Mpro.
Webber, Nakoa Kristen, "Identifying Inhibitors Targeting the Nonstructural Protein 15 and Main Protease of Coronaviruses Using Molecular Docking and Molecular Dynamics Simulation" (2021). Theses and Dissertations. 2948.