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oai:figshare.com:article/30426376 2025-08-01T00:00:00Z portal_693 item_type_8 month_year_08_2025

Development of Small Molecules as Broad-spectrum Filoviral Entry Inhibitors Destiny Durante (19339059) Chemistry Pharmaceutical 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. 2025-08-01T00:00:00Z Text Thesis 10.25417/uic.30426376.v1 https://figshare.com/articles/thesis/Development_of_Small_Molecules_as_Broad-spectrum_Filoviral_Entry_Inhibitors/30426376 In Copyright Open Access after 2027-09-01