Computational Design and Validation of a Human Protein Derived SARS-CoV-2 Virus Inhibitor and Potential Future Directions
Presenter Type
UNO Graduate Student (Masters)
Major/Field of Study
Bioinformatics
Other
Biomedical Informatics
Author ORCID Identifier
0000-0002-6824-0428
Advisor Information
Dario Ghersi
Location
MBSC304 - G (Masters)
Presentation Type
Oral Presentation
Start Date
24-3-2023 2:30 PM
End Date
24-3-2023 3:45 PM
Abstract
SARS-CoV-2 enters human cells via interactions between the surface Spike glycoprotein and the cellular membrane receptor angiotensin-converting enzyme 2 (ACE2). One potential therapeutic route in the response against emerging pathogens like SARS-CoV-2 are entry inhibitors which block this vital interaction. Early in the pandemic, structural information of this interaction became available. Using in-house programs and protein structural analysis tools, we identified a stable fragment of the human surface protein ACE2 that is able to bind to the Spike protein of SARS-CoV-2. Using computational approaches like protein modeling, docking, and molecular dynamics simulations, we investigated the stable fragment capable of binding to Spike. Through our collaboration within the UNMC Biochemistry and Pharmacology departments, we validated the fragment in a wet-lab setting. Finally, we show that our approach to design viral inhibitors has the potential to be extended to other infections following the same methodology.
Scheduling
9:15-10:30 a.m., 10:45 a.m.-Noon, 1-2:15 p.m., 2:30 -3:45 p.m.
Computational Design and Validation of a Human Protein Derived SARS-CoV-2 Virus Inhibitor and Potential Future Directions
MBSC304 - G (Masters)
SARS-CoV-2 enters human cells via interactions between the surface Spike glycoprotein and the cellular membrane receptor angiotensin-converting enzyme 2 (ACE2). One potential therapeutic route in the response against emerging pathogens like SARS-CoV-2 are entry inhibitors which block this vital interaction. Early in the pandemic, structural information of this interaction became available. Using in-house programs and protein structural analysis tools, we identified a stable fragment of the human surface protein ACE2 that is able to bind to the Spike protein of SARS-CoV-2. Using computational approaches like protein modeling, docking, and molecular dynamics simulations, we investigated the stable fragment capable of binding to Spike. Through our collaboration within the UNMC Biochemistry and Pharmacology departments, we validated the fragment in a wet-lab setting. Finally, we show that our approach to design viral inhibitors has the potential to be extended to other infections following the same methodology.