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

Next, we explored basic physical chemical aspects that could offer a simple and quick reasoning to understand the above free energy results and eventually be used as descriptors to scan databases of mAbs to filter promising ideal candidates. Although different driven forces can result in protein-protein complexation, 42, 43 pH and charge-charge interactions seems especially important for viral proteins. 27, 55, [81] [82] [83] [84] [85] Indeed, the protein net charges numbers (Z) obtained as function of the solution pH show that the SARS-CoV-2 S RDB protein is always slightly more positively charged than SARS-CoV-1 S RDB protein at the same physical chemical environment (Z equals to 5.2 and 5.5, respectively, for them at pH 4.6) − see table 1. Since all studied fragments of Abs are also positively charged at pH 4.6 (Z equals to 9.1, 4.2, 2.7, 5.8 for 80R, CR3022, m396 and F26G19, respectively), it can be easily seen that the order observed for the binding affinities above in the free energy analyses do follow a simple charge-charge rule for the mAbs with similar surface area (A~10,000 Å 2 ). For the SARS-CoV-1 S RDB protein, from the weaker to the stronger repulsive cases in terms of the Coulomb contributions (Zi*Zj assuming the same Bjerrum length, salt screening and separation distances 42, 43, 86 ) , the predicted order for the binding affinity is 80R (5.2*9.1=47.3) < F26G19 (5.2*5.8=30.2) < CR3022 (5.2*4.2=21.8). This agrees with the previous free energy analyses (see above). As large is A, larger is the attractive van der Waals interactions that can overcome the charge-charge repulsion. This can also explain why m396 (that is smaller and has roughly half of A) is less attracted to the RBD proteins even being slightly less positively charged (Z equals to 2.7 at pH 4.6) than the others (Z~5-6).