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1 online resource |
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text txt rdacontent |
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computer c rdamedia |
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online resource cr rdacarrier |
| Note |
M.S. Chapman University 2023 |
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Department: Computational and Data Sciences. |
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Committee Advisors: Gennady Verkhivker, Cyril Rakovski, Mohamed Allali. |
| Abstract |
The pandemic caused by the emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019 has caused a global public health crisis of nearly unprecedented scale. In the years following the outbreak, the scientific community has mobilized to develop several vaccines and treatments. Drug repurposing as a strategy for drug development has produced many of the current therapeutic options. The greatest challenge to designing a therapeutic inhibitor of SARS-CoV-2 is the shifting mutational landscape of the virus as it evolves. In this study, we focus on the spike protein as a target for potential inhibitors. We explore two methods of inhibiting spike function, allosteric inhibition and direct inhibition. In the study of allosteric inhibition, we screened two compound libraries against two allosteric sites. In the study of direct inhibition, several top-performing direct inhibitors of the wildtype spike were evaluated against five variants, B.1.1.7, B.1.351, P.1, B.1.617.2, and B.1.1.529. In summary, we identify four potential allosteric inhibitors that warrant further in-vitro study. We also find that the direct potential inhibitors of the wildtype spike had the most similar performance against the B.1.617.2 and B.1.1.7 variants. |
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COVID-19 (Disease)
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Spike Protein.
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Drug repurposing.
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Molecular docking.
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Virtual screening.
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Chapman University -- Thesis and Dissertation.
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Academic theses. lcgft |
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Verkhivker Gennady M., degree supervisor.
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Chapman University. Schmid College of Science and Technology.
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