PME SPECIAL SEMINAR SERIES: Broad Spectrum Antiviral Peptide Engineering for Future Pandemic Preparedness

Viral infections are a leading cause of global morbidity and mortality that urgently need effective therapeutic strategies. While there have been important advances in antiviral drug development over the past few decades, there remain major challenges associated with the large number of emerging and re-emerging viruses as well as with the rise of drug-resistant virus strains. Developing broadspectrum antiviral strategies against multiple viruses is a high priority in countering emerging viral threats. One promising strategy involves utilizing antiviral agents that target the lipid membrane surrounding a wide range of enveloped viruses such as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Zika (ZIKV), and Dengue (DENV). Unlike other antiviral targets, the lipid envelope is derived from host cell membranes, and there is a high barrier to the emergence of drug-resistant virus strains. In this talk, I will present ongoing work on engineering membrane-active peptides that exhibit broad-spectrum antiviral activity against medically important viruses by selectively destabilizing high-curvature viral membranes. By utilizing biophysical assays, we have characterized the mechanism of action of drug candidates down to the single-virus particle level with real-time measurement readouts. We have identified a lead peptide drug candidate that exhibits potent, in vitro antiviral activity against ZIKV and DENV (all four serotypes) at nanomolar concentrations based on these characterization efforts.