UCSF Chimera and AutoDock Vina allow the structure-based design of inhibitors of SARS-CoV-2 M pro as potential drug candidates. Using publicly available X-ray crystallographic structures and free software, anybody can unleash their imagination and try to invent new molecules that might help treat or prevent COVID-19 or other diseases. This tutorial demonstrates the process and provides a simple example of how a published X-ray crystallographic structure can be modified and manipulated with the goal of creating molecules to bind and block a critical enzyme. This tutorial can also be adapted to design inhibitors of other enzymes (e.g., HIV protease) from an X-ray crystallographic or NMR-based structure of an enzyme complex. We hope that this tutorial will help students and scientists design their own inhibitors of SARS-CoV-2 M pro or other drug targets to help discover drugs for the treatment of COVID-19 and other diseases.