 Bicycles are a novel class of antivirals that combine the drug-like advantages of both small molecules and antibodies. They can be rapidly screened for binding to specific targets on virus surfaces, such as SARS-CoV-2 spike, and then modified to create more potent agents. This approach enables the creation of highly effective antivirals against multiple strains of the virus, including those with mutations that have made them resistant to other treatments. In addition, bicycles can be combined together to create multi-targeted agents that can block multiple strains of the virus simultaneously. This article was authored by Catherine Eugena, Marina Vasebird, Maximilian A. J. Harmon, and others.