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Directed Evolution of Nanobodies for COVID-19 Prevention


Stefanie H. Chen
Department of Biological Sciences
North Carolina State University
Andrea Bixler
Biology Department
Clarke University


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).


  • Describe nanobodies and how they differ from antibodies.
  • Articulate the features and purpose of a yeast surface display library.
  • Diagram the process of directed evolution of proteins.
  • Compare and contrast directed evolution with natural selection.
  • Explain how nanobodies can block transmission of SARS-CoV-2.


Directed evolution; natural selection; high-throughput; antibodies; COVID 19; Spike; spike protein; nanobodies; affinity; protein binding; yeast surface display; library; SARS-CoV-2; protein engineering

Topical Areas


Educational Level

Undergraduate lower division, Undergraduate upper division, Graduate



Type / Methods

Directed, Flipped, Jig-Saw



Subject Headings

Biochemistry  |   Biology (General)  |   Biotechnology  |   Evolutionary Biology  |   Molecular Biology  |  

Date Posted


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