Targeting viral envelopes with antiviral peptides and peptoids and degraders, and surface proteins with small molecules

ABSTRACT. Our overall objective is to develop a new class of direct acting-antivirals (DAAs) that can specifically target viral envelopes but not host cell membranes using our novel amphipathic, α-helical (AH) Lipid Envelope Antiviral Disruption (LEAD) peptides and peptoids (sequence-specific N-substituted glycine oligomers). Therapeutics that can specifically target enveloped viruses have the potential to counteract severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and a wide variety of RNA viruses of pandemic potential. One promising target is the lipid membrane coating that surrounds enveloped viruses, as membrane disruption can abrogate viral infectivity. This team’s investigators have developed a new class of AH peptides, and another new type of self-assembling amphipathic peptoids, that selectively form pores in high-curvature membranes such as membrane-enveloped virus particles (