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.
","abstract_html":"<p>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.</p>","abstract_has_math":false,"creators":["Gupta, Grace"],"institution":null,"degree_name":"Master of Science (MS)","degree_level":"Thesis","degree_discipline":"Computational and Data Sciences","degree_department":null,"school":null,"contributors":["Gennady Verkhivker","Cyril Rakovski","Mohamed Allali"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2023,"date_issued":"2023-12-01T08:00:00Z","date_published":"2023-12-01T08:00:00Z","updated_at":"2026-07-24T01:38:31Z","subjects":["drug repurposing","virtual screening","molecular docking","SARS-CoV-2","spike protein","Bioinformatics"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.chapman.edu/cads_theses/18","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Gennady Verkhivker","Cyril Rakovski","Mohamed Allali"]},{"key":"dc:creator","label":"Author","values":["Gupta, Grace"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"thesis:degree_discipline","label":"Discipline","values":["Computational and Data Sciences"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Thesis"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Master of Science (MS)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["drug repurposing","virtual screening","molecular docking","SARS-CoV-2","spike protein","Bioinformatics"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://digitalcommons.chapman.edu/cads_theses/18"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["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.
"]},{"key":"dc:source","label":"Dc Source","values":["G. Gupta, \"Computational molecular docking studies of small molecule inhibitors with the SARS-CoV-2 spike protein variants: In-silico drug discovery using virtual screening and drug repurposing approaches,\" M. S. thesis, Chapman University, Orange, CA, 2023. https://doi.org/10.36837/chapman.000515"]},{"key":"dc:title","label":"Title","values":["Computational Molecular Docking Studies of Small Molecule Inhibitors With the SARS-CoV-2 Spike Protein Variants: In-Silico Drug Discovery Using Virtual Screening and Drug Repurposing Approaches"]}]}],"canonical_facts":{"dc:contributor":["Gennady Verkhivker","Cyril Rakovski","Mohamed Allali"],"dc:creator":["Gupta, Grace"],"dc:description.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.
"],"dc:identifier":["https://digitalcommons.chapman.edu/cads_theses/18"],"dc:source":["G. Gupta, \"Computational molecular docking studies of small molecule inhibitors with the SARS-CoV-2 spike protein variants: In-silico drug discovery using virtual screening and drug repurposing approaches,\" M. S. thesis, Chapman University, Orange, CA, 2023. https://doi.org/10.36837/chapman.000515"],"dc:subject":["drug repurposing","virtual screening","molecular docking","SARS-CoV-2","spike protein","Bioinformatics"],"dc:title":["Computational Molecular Docking Studies of Small Molecule Inhibitors With the SARS-CoV-2 Spike Protein Variants: In-Silico Drug Discovery Using Virtual Screening and Drug Repurposing Approaches"],"thesis:degree_discipline":["Computational and Data Sciences"],"thesis:degree_level":["Thesis"],"thesis:degree_name":["Master of Science (MS)"]},"updated_at":"2026-07-24T01:38:31Z"}