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

. 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 It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the .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 Analyzing the interactions between these RBD proteins and the SARS-CoV-1 S RBD specific neutralizing mAbs (80R, F26G19, m396, CR3022) allowed us to reproduce the experimental results. The only mAb with measured affinities for the SARS-CoV-2 S RBD protein by BLI assay was CR3020 8 which was also the one with higher affinity quantified in the present theoretical study. Moreover, we could map their electrostatic epitopes and identify that all mAbs tend to share the same titratable residues, and they are like the residues involved in the interaction with ACE2. However, the RBD protein responsible for COVID-19 clearly has more titratable residues interacting with ACE2 than its precursor suggesting that its binding to ACE2 might be less specific. This can explain the general difficulty that mAbs can experience to completely block the SARS-CoV-2 S RBD-ACE2 interaction.