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

Several molecular systems were investigated in the present study employing the two SARS-CoV-1 and 2 S RBD proteins (see Figure 1 ) with ACE2 and the fragments of the mAbs 80R, CR3022, m396, and F26G29. Typically, these fragments of mAbs are fusion proteins from . CC-BY-NC-ND 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the .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 variable regions of the heavy and light chains of immunoglobulins connected with a short linker peptide. Additional calculations were carried out for the SARS-CoV-2 S RBD with a new proposed mAb based on CR3022. For most of these macromolecules, three dimensional crystallographic structures are available at the RCSB Protein Data Bank (PDB): 44 a) the SARS-CoV-1 S RBD protein was extracted from the PDB id 2AJF (chain E, resolution 2.9Å, pH 7.5) where it was found complexed with ACE2 (chain A) − see Figure 2 ; b) the fragment of the Ab 80R was taken out from the PDB id 2GHW (chain B, resolution 2.3Å, pH 4.6); c) the anti-SARS-CoV-1 m396 Ab was extracted from the PDB id 2G75 (chains A and B, resolution 2.28Å, pH 8.5) removing part of the chains to keep only the variable regions and the short linker peptide; d) F26G19 Fab was taken out from PDB id 3BGF (chains L and C, resolution 3.0Å, pH 5.5), following the same procedure used for m396. Missing regions in these proteins were built up using the "UCSF Chimera 1.11.2" interface 45 of the program "Modeller" with default parameters. 46 Figure 3 shows their final three-dimensional structures as used in this work. All PDB files were edited before the calculations. Water molecules and hetero atoms were completely removed from all used files. The "UCSF Chimera 1.11.2" package 45 was employed for all molecular visualizations and representations too.