Date of Award
4-22-2023
Document Type
Thesis
Department
Chemistry
First Advisor
Carol A. Parish
Second Advisor
Mike Norris
Abstract
In December 2019, a novel coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV-2), was identified in Wuhan, China after numerous patients experienced pneumonia symptoms, but existing medicinal treatments were ineffective.1 The global spread of the SARS-CoV-2 virus caused an outbreak of the infectious disease, coronavirus disease 2019 (COVID-19), which was soon after declared a pandemic by the World Health Organization, referred to as the COVID-19 pandemic. According to John Hopkins University, over 1,000,000 people have died from SARS-CoV-2 infection and about 104,000,000 cases have been confirmed in the United States (US). An infection of the SARS-CoV-2 virus is caused by the virus spike protein binding with the human angiotensin-converting enzyme (hACE2) receptor. The most common symptoms reported of this respiratory disease are a cough, fever, difficulty breathing, fatigue, headache, sore throat, loss of taste or smell, congestion, nausea, vomiting, and diarrhea. Patients with severe cases can experience dyspnea, hypoxemia, and progressive respiratory failure which can result in organ failure or other fatal conditions. Groups over the age of 60 and/or those with pre-existing conditions can experience a higher rate of fatality. The hACE2 receptors, located on the surface of human throat cells and lung epithelial cells, are SARS-CoV-2 targets.The function of this receptor is to aid the regulation of the renin-angiotensin system (RAS), which modulates both blood pressure and extracellular volume.The hACE2 receptor is an enzyme which converts the substrate angiotensin II to the active form. The active form, angiotensin I-7, acts as a vasodilator.The direct interaction between the SARS-CoV-2 spike protein and the hACE2 receptor causes viral infection. SARS-CoV-2 contains spike-like projections of glycoproteins on its surface that are responsible for host infection. Specifically, the ectodomain of the SARS-CoV-2 virus consists of a subunit, S1, which contains the receptor-binding domain (RBD) and the membrane-fusion subunit, S2.10 The SARS-CoV-2 RBD consists of a section of amino acids that interact directly with the hACE2 receptor called the receptor binding motif (RBM).
Recommended Citation
Carter, Camryn, "The Characterization of the SARS-CoV-2 Receptor Binding Domain Interaction with the Human ACE2 Receptor and Potential Small Molecule Inhibitors" (2023). Honors Theses. 1666.
https://scholarship.richmond.edu/honors-theses/1666