Development of a novel therapeutic against coronaviruses
| dc.contributor.author | Pho, Yvonne | |
| dc.contributor.examiningcommittee | Drebot, Mike (Medical Microbiology and Infectious Diseases) Babiuk, Shawn (Immunology) | en_US |
| dc.contributor.supervisor | Kobasa, Darwyn (Medical Microbiology and Infectious Diseases) | en_US |
| dc.date.accessioned | 2019-09-04T21:57:00Z | |
| dc.date.available | 2019-09-04T21:57:00Z | |
| dc.date.issued | 2019-08-14 | en_US |
| dc.date.submitted | 2019-08-14T13:49:31Z | en |
| dc.date.submitted | 2019-09-04T19:25:36Z | en |
| dc.degree.discipline | Medical Microbiology and Infectious Diseases | en_US |
| dc.degree.level | Master of Science (M.Sc.) | en_US |
| dc.description.abstract | Although people around the world are commonly infected with coronaviruses, some of these pathogens are high on the list of public health concerns. The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) in the last two decades has shown the pandemic potential of this rapidly adapting virus family. Treatment of MERS has been problematic as traditional antivirals were not shown to be effective against this pathogenic strain of coronavirus. Moreover, development of vaccines and therapeutics has been hindered by the lack of a commercially available permissive small animal for MERS-CoV. These circumstances contrast those seen in the emergence of SARS-CoV where some small animal models were susceptible to virus infection without aid, and moreover, with serial passaging of a SARS-CoV strain in mice a mouse-adapted variant was developed that was able to cause severe respiratory disease and death in mice. This work aims to develop and evaluate a therapeutic that specifically targets a coronavirus while developing a small animal model that allows MERS-CoV infection. I showed that the fusion of the ectodomain of the SARS-CoV host cell target receptor angiotensin converting enzyme 2 (ACE2) to mouse IgG Fc exhibits promising antiviral activity in vitro. This approach, if effective in subsequent in vivo evaluations, could be applied to in the generation of a treatment against MERS-CoV. Additionally, I was able to show that mice were permissive to MERS-CoV infection following transduction of their airways with an adenovirus vector expressing human host-cell receptor for MERS-CoV, dipeptidyl peptidase 4 (hDPP4), although I was not successful in further enhancing the efficacy of airway transduction using Adeno- II associated viral vector deliver of hDPP4. Altogether, this study contributes to the development and evaluation of therapeutics against current and potential emerging coronaviruses. | en_US |
| dc.description.note | October 2019 | en_US |
| dc.identifier.uri | http://hdl.handle.net/1993/34160 | |
| dc.language.iso | eng | en_US |
| dc.rights | open access | en_US |
| dc.subject | Therapeutic development | en_US |
| dc.subject | Coronavirus | en_US |
| dc.title | Development of a novel therapeutic against coronaviruses | en_US |
| dc.type | master thesis | en_US |