Atomically Precise Polyanionic Boron Cluster Agents with Broad-Spectrum Antiviral Activity

The development of antivirals capable of addressing infections from multiple viruses is critically needed, as underscored by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and ongoing annual influenza epidemics. Polyanionic polymer and hybrid gold nanoparticle (AuNP) systems have both previously shown significant infection inhibition activity against a wide variety of enveloped viruses. However, both of these systems exhibit variability in molecular weight and charge density distribution, which makes detailed structure-activity relationships difficult to ascertain. In this work, we report the synthesis of well-defined, dodecaborate-based clusters that are densely surface functionalized with charged ligands. These compounds exhibit minimal cytotoxic effects against mammalian cells, and several structures possess promising antiviral activity against both human immunodeficiency virus (HIV-1) and cytomegalovirus (CMV). This library of compounds offers a promising scaffold from which the roles of ligand identity, molecule size, and charge density on antiviral activity can be further studied and may ultimately help guide future design of antiviral agents.