Abstract
We identified and explored the structure-activity-relationship (SAR) of an adamantane carboxamide chemical series of Ebola virus (EBOV) inhibitors. Selected analogs exhibited half-maximal inhibitory concentrations (EC50 values) of ∼10-15 nM in vesicular stomatitis virus (VSV) pseudotyped EBOV (pEBOV) infectivity assays, low hundred nanomolar EC50 activity against wild type EBOV, aqueous solubility >20 mg/mL, and attractive metabolic stability in human and nonhuman liver microsomes. X-ray cocrystallographic characterizations of a lead compound with the EBOV glycoprotein (GP) established the EBOV GP as a target for direct compound inhibitory activity and further provided relevant structural models that may assist in identifying optimized therapeutic candidates.
Original language | English (US) |
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Pages (from-to) | 1160-1167 |
Number of pages | 8 |
Journal | ACS Medicinal Chemistry Letters |
Volume | 11 |
Issue number | 6 |
DOIs | |
State | Published - Jun 11 2020 |
Keywords
- Ebola virus
- adamantane carboxamide
- cell entry
- glycoprotein
ASJC Scopus subject areas
- Biochemistry
- Drug Discovery
- Organic Chemistry