Key Points
- Determine the critical chemical functionalities at the C2 position of enviroxime that govern antiviral activity against rhinoviruses and enteroviruses.
- Synthesized a series of C2-substituted enviroxime analogs to assess structure-activity relationships.
- Conducted ab initio computational modeling to investigate steric interactions and conformational flexibility near the N3 position.
- Tested the antiviral efficacy of synthesized analogs against rhinoviruses and enteroviruses in tissue culture.
- Analogs bearing a primary amino substitution at C2 displayed the highest antiviral activity among all tested modifications.
- Bulky C2 substituents created repulsive steric strain at N3, which severely reduced antiviral potency when conformational flexibility was constrained.
- Strong intramolecular hydrogen bonding between the C2 amino hydrogen and the N1 sulfonyl oxygen fixed the adjacent hydrogen in an optimal orientation for target engagement.
Structured PICO
PPopulationTissue culture models for rhinoviruses and enteroviruses
IInterventionC2-substituted analogs of Enviroxime
OOutcomeAntiviral activity
Primary amino substitution at the C2 position of Enviroxime analogs optimizes antiviral activity by facilitating favorable hydrogen bonding.