SARS-CoV-2 is a highly infectious virus that causes COVID-19, a serious respiratory infection that has caused over 23 million infections and over 800,000 deaths worldwide, as of 08/23/20. 1 SARS-CoV-2 causes infected cells to express a main protease (M pro or 3CL protease) that is responsible for sitespecifically cleaving the polyprotein, which is translated from viral mRNA within human cells. The proteolytic activity of M pro is essential for the virus to generate the individual proteins that are necessary for replication and infection. The essential role of M pro , as well as the success of HIV protease inhibitors in the treatment of HIV/AIDS, make M pro an attractive therapeutic target to treat COVID-19. Proteases are enzymes that cleave polypeptide chains, hydrolyzing an amide bond within the polypeptide chain. Once the polypeptide is bound within the active site of the protease, the scissile amide bond is hydrolyzed to generate a carboxylic acid and amine (Figure ). The binding pockets of a protease are referred to as subsites, denoted by "S". Typically, each subsite interacts with a specific side chain of the polypeptide substrate, denoted by "P". The position at which the polypeptide substrate is cleaved determines the assignment of prime or no-prime notation. Prime notation refers to the C-terminal side and no-prime notation refers to the N-terminal side of the polypeptide and corresponding pockets (Figure ). In this tutorial, we will use the X-ray crystallographic structure of the homologous SARS-CoV M pro bound to a protein substrate to recapitulate the design of a cyclic peptide inhibitor of the SARS-CoV-2 M pro . We will first use the molecular modeling software UCSF Chimera to visualize the X-ray crystallographic structure of the SARS-CoV M pro bound to the protein substrate. We will then modify the protein substrate to create a model of the cyclic peptide inhibitor within the SARS-CoV M pro . Finally, we will use AutoDock Vina to evaluate this model, by docking the inhibitor to SARS-CoV M pro and then to SARS-CoV-2 M pro . We have selected these software packages, because they can be downloaded without cost and are easy to learn. These and other molecular modeling studies helped our laboratory decide to pursue the synthesis of the cyclic peptide and experimentally evaluate its promise as an inhibitor of SARS-CoV-2 M pro . In an accompanying preprint in bioRxiv, we describe the synthesis of the cyclic peptide and the experimental validation as an inhibitor of SARS-CoV-2 M pro . Here, we provide the rationale and then overview the process of designing the inhibitor with UCSF Chimera and evaluating it with AutoDock Vina. In the supporting information (SI), we provide an illustrated step-by-step protocol, as well as a video showing the inhibitor design process, to teach others how to execute the design process. We anticipate this tutorial will help students and scientists use free software to design their own drug candidates for COVID-19 and the coronaviruses that will cause future pandemics.