Date Approved

9-27-2021

Embargo Period

9-28-2021

Document Type

Thesis

Degree Name

M.S. Bioinformatics

Department

Molecular and Cellular Biosciences

College

College of Science & Mathematics

Advisor

Nathaniel V. Nucci Ph.D.

Committee Member 1

Benjamin Carone Ph.D.

Committee Member 2

Yong Chen Ph.D.

Keywords

coronaviruses, SARS-CoV-2

Subject(s)

Antiviral agents; Computer simulation

Disciplines

Bioinformatics | Medicine and Health Sciences

Abstract

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.

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