Publication Date

12-1-2020

Document Type

Article

First Advisor

Hagen, Timothy J.

Degree Name

B.S. (Bachelor of Science)

Department

Department of Chemistry and Biochemistry

Abstract

The papain-like protease (PLpro) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a target enzyme for treatment of the 2019 coronavirus infectious disease (COVID-19). Multiple lead competitive inhibitors to the protease have been previously discovered, particularly VIR250, HGN1034, and GYX402. Analogs of these ligands were designed using ChemSketch or Chem3D. The ligand-active site interactions of those unique ligands were observed and compared using AutoDock Tools, which also computes a predicted inhibitory constant (K​i)​ . Over the Fall 2020 semester, proficiency in performing several functions of AutoDock Tools was acquired, and a total of thirteen unique and original compounds designed based on the aforementioned leads were tested. Three analogs of HGN1034 showed to have the strongest potential for future research and application: ZDM16 had the closest docking pose to the lead HGN1034 (K​i ZDM16​ = 329.04 nM); ZDM13 and ZDM14 had the lowest computed inhibitory constants, lower than that of HGN1034 (K​i ZDM14​ = 15.96 nM < K​i ZDM13​ = 16.45 nM < K​i HGN1034​ = 19.78 nM). The limitations of computational chemistry are considered and rationalized, and prospective follow-up studies and possibilities for future designs of inhibitors of the SARS-CoV-2 PLpro enzyme are discussed.

Comments

A Contemporary Exploration of the Field of Drug Design and Discovery

Extent

14 pages

Language

eng

Publisher

Northern Illinois University

Rights Statement

In Copyright

Rights Statement 2

NIU theses are protected by copyright. They may be viewed from Huskie Commons for any purpose, but reproduction or distribution in any format is prohibited without the written permission of the authors.

Alt Title

Drug Design and Discovery for COVID-19 Treatment

Media Type

Text

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