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Discovery and In Vitro Characterization of Novel Coronavirus NSP13 Helicase Inhibitors

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Helicases are essential enzymes in coronavirus replication but have historically proven difficult to drug. The SARS-CoV-2 NSP13 helicase, conserved across coronaviruses and central to viral RNA synthesis, represents a compelling antiviral target that remains largely unexploited. This poster describes a multi-assay screening campaign conducted by IRBM, combining ATPase and unwinding assays to screen the IRBM small molecule library, followed by dose-response profiling and counter-screens to triage hits. Confirmed inhibitors display a time-dependent, irreversible inhibition profile, supported by jump dilution experiments and HRMS intact mass analysis, with selectivity over human helicases and key SARS-CoV-2 enzymes. Download the poster to explore the screening funnel, mechanistic characterization data, and structure-activity findings in detail.

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