pan-respiratory antiviral chemotype

A novel small molecule chemotype with broad-spectrum antiviral activity against major respiratory viruses. Identified via a cell-free protein synthesis and assembly-based phenotypic screen for modulation of viral capsid assembly, this chemotype (exemplified by PAV-431 and its advanced analog PAV-104) targets a transient host multi-protein complex containing the 14-3-3 protein. The compound binds selectively to a virally modified subset of 14-3-3 within this complex, which is implicated in both viral life cycles and innate immunity. By restoring the composition of this complex altered during infection, the drug disrupts viral replication across all six families of viruses responsible for most human respiratory diseases (including coronaviruses and paramyxoviruses). Efficacy has been demonstrated in cell culture models as well as animal models (e.g., porcine epidemic diarrhea virus and respiratory syncytial virus). The advanced analog PAV-104 shows improved selectivity for virally modified targets, reducing host toxicity. This approach represents a new paradigm targeting the host-virus interface rather than direct viral components[1][5][6].