{"id":{"repo_id":"uic","oai_identifier":"oai:figshare.com:article/30426376"},"canonical_url":"https://search.dev.ndltd.org/etd/uic/oai:figshare.com:article/30426376","repository":{"repo_id":"uic","name":"University of Illinois - Chicago","base_url":"https://api.figshare.com/v2/oai"},"display":{"title":"Development of Small Molecules as Broad-spectrum Filoviral Entry Inhibitors","abstract":"Ebola (EBOV) and Marburg (MARV) filoviruses are priority infectious agents due to their high pathogenicity and lethality in infected patients. The current lack of pan-filoviral therapeutics exemplifies the need for effective treatments against diverse filoviruses. The filoviral glycoprotein (GP) has proven to be a drug-targetable site as it is conserved amongst all filoviruses and is used to mediate several steps in filoviral entry. In the effort to develop broad-spectrum antifilovirals, a series of N-substituted pyrrole-based heterocycles and elacestrant derivatives were developed to target GP and effectively inhibit diverse filoviral entry in a pseudovirus assay. Selectivity, potency, and metabolic stability of these viral entry inhibitors were improved by introducing structural modifications. In addition, antiviral activity was validated using replication-competent EBOV and MARV, mutational analysis was used to identify the suggested EBOV GP binding region, and antiviral counter-screens demonstrated reduced off-target activity for these filoviral entry inhibitors. Excellent activity coupled with favorable drug-like properties support these entry inhibitors as promising broad-spectrum antifilovirals.","abstract_html":"Ebola (EBOV) and Marburg (MARV) filoviruses are priority infectious agents due to their high pathogenicity and lethality in infected patients. The current lack of pan-filoviral therapeutics exemplifies the need for effective treatments against diverse filoviruses. The filoviral glycoprotein (GP) has proven to be a drug-targetable site as it is conserved amongst all filoviruses and is used to mediate several steps in filoviral entry. In the effort to develop broad-spectrum antifilovirals, a series of N-substituted pyrrole-based heterocycles and elacestrant derivatives were developed to target GP and effectively inhibit diverse filoviral entry in a pseudovirus assay. Selectivity, potency, and metabolic stability of these viral entry inhibitors were improved by introducing structural modifications. In addition, antiviral activity was validated using replication-competent EBOV and MARV, mutational analysis was used to identify the suggested EBOV GP binding region, and antiviral counter-screens demonstrated reduced off-target activity for these filoviral entry inhibitors. Excellent activity coupled with favorable drug-like properties support these entry inhibitors as promising broad-spectrum antifilovirals.","abstract_has_math":false,"creators":["Destiny Durante (19339059)"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025-08-01T00:00:00Z","date_published":"2025-08-01T00:00:00Z","updated_at":"2026-07-27T21:34:56Z","subjects":["Chemistry","Pharmaceutical"],"languages":[],"rights":["In Copyright","Open Access after 2027-09-01"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://doi.org/10.25417/uic.30426376.v1","outbound_label":"DOI","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Destiny Durante (19339059)"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2025-08-01T00:00:00Z"]},{"key":"dc:relation","label":"Dc Relation","values":["https://figshare.com/articles/thesis/Development_of_Small_Molecules_as_Broad-spectrum_Filoviral_Entry_Inhibitors/30426376"]},{"key":"dc:type","label":"Dc Type","values":["Text","Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Chemistry","Pharmaceutical"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:rights","label":"Dc Rights","values":["In Copyright","Open Access after 2027-09-01"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["10.25417/uic.30426376.v1"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Ebola (EBOV) and Marburg (MARV) filoviruses are priority infectious agents due to their high pathogenicity and lethality in infected patients. The current lack of pan-filoviral therapeutics exemplifies the need for effective treatments against diverse filoviruses. The filoviral glycoprotein (GP) has proven to be a drug-targetable site as it is conserved amongst all filoviruses and is used to mediate several steps in filoviral entry. In the effort to develop broad-spectrum antifilovirals, a series of N-substituted pyrrole-based heterocycles and elacestrant derivatives were developed to target GP and effectively inhibit diverse filoviral entry in a pseudovirus assay. Selectivity, potency, and metabolic stability of these viral entry inhibitors were improved by introducing structural modifications. In addition, antiviral activity was validated using replication-competent EBOV and MARV, mutational analysis was used to identify the suggested EBOV GP binding region, and antiviral counter-screens demonstrated reduced off-target activity for these filoviral entry inhibitors. Excellent activity coupled with favorable drug-like properties support these entry inhibitors as promising broad-spectrum antifilovirals."]},{"key":"dc:title","label":"Title","values":["Development of Small Molecules as Broad-spectrum Filoviral Entry Inhibitors"]}]}],"canonical_facts":{"dc:creator":["Destiny Durante (19339059)"],"dc:date":["2025-08-01T00:00:00Z"],"dc:description":["Ebola (EBOV) and Marburg (MARV) filoviruses are priority infectious agents due to their high pathogenicity and lethality in infected patients. The current lack of pan-filoviral therapeutics exemplifies the need for effective treatments against diverse filoviruses. The filoviral glycoprotein (GP) has proven to be a drug-targetable site as it is conserved amongst all filoviruses and is used to mediate several steps in filoviral entry. In the effort to develop broad-spectrum antifilovirals, a series of N-substituted pyrrole-based heterocycles and elacestrant derivatives were developed to target GP and effectively inhibit diverse filoviral entry in a pseudovirus assay. Selectivity, potency, and metabolic stability of these viral entry inhibitors were improved by introducing structural modifications. In addition, antiviral activity was validated using replication-competent EBOV and MARV, mutational analysis was used to identify the suggested EBOV GP binding region, and antiviral counter-screens demonstrated reduced off-target activity for these filoviral entry inhibitors. Excellent activity coupled with favorable drug-like properties support these entry inhibitors as promising broad-spectrum antifilovirals."],"dc:identifier":["10.25417/uic.30426376.v1"],"dc:relation":["https://figshare.com/articles/thesis/Development_of_Small_Molecules_as_Broad-spectrum_Filoviral_Entry_Inhibitors/30426376"],"dc:rights":["In Copyright","Open Access after 2027-09-01"],"dc:subject":["Chemistry","Pharmaceutical"],"dc:title":["Development of Small Molecules as Broad-spectrum Filoviral Entry Inhibitors"],"dc:type":["Text","Thesis"]},"updated_at":"2026-07-27T21:34:56Z"}