A new highly pathogenic coronavirus (SARS-CoV-2, provisionally named 2019-nCoV) has swept the world since December 2019. The key to responding to this outbreak is to understand the pathogenic mechanism of the virus. Our understanding of the viral infection process at the molecular and atomic levels depends on the ability to map the structural details of individual biological macromolecules and their interactions with each other and with small molecules. The determination of the three-dimensional (3D) structures of proteins is essential for understanding these interactions and their structure-function relationships, which is beneficial for scientists to develop more effective preventive or therapeutic drugs more quickly. With advanced facilities and years of experience in crystallization and structure determination, Creative Biostructure provides flexible X-ray crystallography services covering all technical stages from gene synthesis to structural analysis to support coronavirus-related research.
The crystal structure of the SARS-CoV-2 spike receptor binding domain (RBD) bound to the cell receptor ACE2 has been identified by X-ray crystallography technology, which helps us better understand the initial steps of novel coronavirus infection at the atomic level. The overall binding pattern of SARS-CoV-2 RBD and ACE2 is almost the same as that of SARS-CoV RBD, which also uses ACE2 as a cell receptor. In addition, the scientists used a high-intensity X-ray source to make an in-depth analysis of the main protease (Mpro, also known as 3-chymotrypsin-like protease, 3CLpro) of SARS-CoV-2. The results of these crystallographic studies are important for the development of antiviral drugs and vaccines.
Figure 1. 3D structure of SARS-CoV-2 Mpro in two different views. (Zhang L.; et al. 2020)
The technology is not limited by the molecular weight of the sample. In addition, the algorithm for protein structural analysis using this technology is well developed, and the reconstructed model has high confidence. With this technique, you can obtain a 3D structure of individual protein/protein-small molecule complex/protein-protein complex with high atomic resolution. This structural information improves to understand protein function and will facilitate the development of coronavirus antiviral drugs.
Creative Biostructure's X-ray crystallography services for coronavirus research are very flexible, including experimental drug screening of validated antiviral drug target structures, as well as customized gene-to-structure service. Our services not only involve the determination of individual protein crystal structure, but also include co-crystallization and structure determination of protein-protein complexes/protein-ligand complexes. We developed a high-throughput X-ray crystallography pipeline that includes cloning, expression, and purification of proteins, followed by protein crystallization and high-resolution crystal structure determination. The gene-to-structure services for coronavirus research are performed on a fee-for-service basis and include: