On the interactions of the receptor-binding domain of SARS-CoV-1 and SARS-CoV-2 spike proteins with monoclonal antibodies and the receptor ACE2

Carolina Corrêa Giron; Aatto Laaksonen; Fernando L. Barroso da Silva

When this study started, no experimental structure was available for the RBD of SARS-CoV-2 S protein. A model was built up at the SWISS-MODEL workspace (YP_009724390.1) based on the NCBI reference sequence NC_045512. 47 The root-mean-square deviation (RMSD) of atomic positions between this modeled structure for the RBD of SARS-CoV-2 S protein and the available one for SARS-CoV-1 (PDB id 2AJF) is 0.638â„«. The structural comparison between the RBD proteins of both SARS viruses can be seen in Figure 1 . Recently, new experimental structures were solved. For example, a cryo-EM structure is now available for the prefusion S glycoprotein with a single incomplete RBD (PDB id 6VSB, resolution 3.46Ã…). The RMSD between our model and the S RBD (chain A) from this structure is 0.790â„«. This number is closer to the RMSD differences between two chains of the same experimental (PDB id 6VSB) trimer structure (e.g. 0.668â„« for chain A x chain B, and 0.732â„« for chain A x chain C). Such diversity of possible conformations might motivate further studies exploring their effects on the theoretical predictions. These RMSD values also indicate that the modeled structure for the SARS-CoV-2 virus as used here is reasonable and within the expected conformational fluctuations from any other structure that could have been chosen for this work. Moreover, an intrinsic assumption here is that an experimental structure obtained at a given and specific physical chemical condition (ionic strength, pH, PEG6000 concentration, etc.) is valid in another condition. 27 The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.05.026377 doi: bioRxiv preprint Only standard amino acids of chain A (ACE2) and E (SARS-CoV-1 S RBD) are shown in a molecular representation using spheres for its atoms. Atoms are colored accordingly to their amino acids physical chemical properties: red for acid amino acids, blue for base amino acids and gray for non-titrating amino acids. For a better visualization of the interface, the ACE2 structure was translated ~12 â„«.