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

We tested the van der Waals (vdw) contribution comparing w(r) for CR3022 and m396 in a model where all electrostatic interactions where completely switched off and only vdw interactions are considered. This test-case system is shown in Figure S1 . It can be seen that m396 in this hypothetical test does have a weaker binding affinity to SARS-CoV-2 S RBD protein in comparison to CR3022 confirming the arguments above presented. and R194) can be seen in Figure 7 at the wild type structure of CR3022. The main physical chemical reasoning to design this new functional molecule was to reduce the net charge of . 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 It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the .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 CR3022 in general together with a decrease of the repulsion for groups that are closely located at the host-pathogen interface. Two amino acids substitutions (K170A and R194A) are suggested at this biological interface while the other one (K12E) is more peripheral (see Figure 7 ). Doing such mutations, the Z of the new molecule (labeled CR3022') drops down from +4.2 to +1.2 at pH 4.6 and from +1.0 to −3.0 at pH 7.0.