Abstract
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 (Mpro) 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 Mpro 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 Mpro and the highly homologous SARS-CoV-2 Mpro. The supporting information provides an illustrated step-by-step protocol, as well as a video showing the inhibitor design process, 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 Mpro.
【저자키워드】 SARS-CoV-2, Main protease (Mpro) inhibitor, UCSF Chimera, AutoDock vina, Structure-based drug design (SBDD), Molecular modeling tutorial, 【초록키워드】 COVID-19, coronavirus, pandemic, protocol, drug design, SARS-CoV, peptide, molecular docking, drug, protease, MPro, SARS-CoV-2 Mpro, X-ray, Pandemics, structure-based design, SARS Coronavirus, inhibitor, information, homologous, AutoDock, Interaction, structures, experimental validation, help, drug candidate, Peptide inhibitor, provide, modify, disseminate, X-ray crystallographic structure, 【제목키워드】 COVID-19, drug design, protease, inhibitor, the SARS-CoV-2,