This paper describes the structure-based design of a preliminary drug candidate against COVID-19 using free software and publicly available X-ray crystallographic structures. The goal of this tutorial is to disseminate skills in structure-based drug design and to allow others to unleash their own creativity to design new drugs to fight the current pandemic. The tutorial begins with the X-ray crystallographic structure of the main protease (M pro ) of the SARS coronavirus (SARS-CoV) bound to a peptide substrate and then uses the UCSF Chimera software to modify the substrate to create a cyclic peptide inhibitor within the M pro active site. Finally, the tutorial uses the molecular docking software AutoDock Vina to show the interaction of the cyclic peptide inhibitor with both SARS-CoV M pro and the highly homologous SARS-CoV-2 M pro . The supporting information (supplementary material) provides an illustrated step-by-step guide for the inhibitor design, to help readers design their own drug candidates for COVID-19 and the coronaviruses that will cause future pandemics. An accompanying preprint in bioRxiv [ https://doi.org/10.1101/2020.08.03.234872 ] describes the synthesis of the cyclic peptide and the experimental validation as an inhibitor of SARS-CoV-2 M pro .
【초록키워드】 COVID-19, SARS-CoV-2, coronavirus, pandemic, drug design, SARS-CoV, peptide, molecular docking, drug, protease, X-ray, Pandemics, structure-based design, SARS Coronavirus, inhibitor, information, homologous, AutoDock, Interaction, structures, UCSF Chimera, supplementary material, experimental validation, M pro, help, drug candidate, Peptide inhibitor, provide, SARS-CoV M, modify, disseminate, X-ray crystallographic structure, 【제목키워드】 COVID-19, drug, tutorial, student, scientist, Free, the SARS-CoV-2,