Directed evolution is a laboratory process that mimics the steps of natural selection to efficiently determine variants of proteins or organisms that respond more effectively to a selected condition. This process was recognized by the 2018 Nobel Prize in Chemistry awarded to Dr. Frances Arnold and has widespread applications, ranging from industrial enzymes to food-producing yeast. Recently, this technology has been applied to identifying and improving potential therapeutics to protect against infection by SARS-CoV-2, the virus that causes COVID-19. In this jigsaw case study, students become experts on the various components of such research (including directed evolution, yeast surface display, nanobodies, and protein binding) before teaching their peers and applying their newly acquired knowledge to the interpretation of a primary research article on SARS-CoV-2. As a concluding activity, students create a concept map or diagram connecting the directed evolution process to natural selection. The case includes two levels of sophistication, which are clearly indicated: introductory (Level 1) and advanced (Level 2). The case was developed for use in either an introductory biology or genetics course (Level 1) or an upper-level molecular biology course (Level 2).