Novel Small-Molecule Inhibitors of Coronavirus Discontinuous Transcription Identified through Integrated Screening Approaches

About this poster

All Coronaviruses, including the highly pathogenic SARS-CoV and SARS-CoV-2, exploit a conserved discontinuous transcription mechanism to produce the subgenomic RNAs required for viral assembly, making this process an attractive target for broad-spectrum antiviral development. This poster presents a comprehensive screening strategy that includes both a phenotypic approach — using a SARS-CoV stable replicon cell line and a >400K compound collection — and an RNA-targeted approach employing biophysical methods against conserved 5′UTR stem-loop elements. Together, these workflows have led to the identification of two structurally distinct small-molecule inhibitors with nanomolar potency that selectively disrupt subgenomic RNA synthesis, as well as validated RNA-binding hits with confirmed direct interaction through NMR analyses. Download the poster to explore the complete screening cascade, mechanistic data, and findings related to structure–activity relationship in detail.