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

However, we prefer to interpret such small differences as tendencies of the system. Based on previous studies 27, 42, 43, 54, 60 where we have observed either that the computed complexation was weaker than the experimental measurements or too much stronger, we feel safer to use this data (and the others discussed below) in relative terms (i.e. comparing different situations). This allows us to successfully predict experimental observations respecting the limits of such CG models. 27, 42, 43, 54 The similarities between their free energy minima are relatively amplified at pH 4.6 ( βwmin=0.07 as seen above) in comparison with pH 7.0 where βwmin is −1.11 and −1.06 ( βwmin=0.05). Both viral S RBD proteins have their affinities to ACE2 slightly raised when pH is increased from the acid to the neutral regime. This somewhat higher binding affinity at neutral pH suggests that the role of pH for RBD proteins constantly under debate at the literature 22, 25, 73, 80 might not be so critical for the infection. It also reinforces the possibility that the viral cell invasion is not a pH-dependent process. Indeed, it seems that pH is more relevant for the next steps to continue the viral infection and not at the first entry level. This possible non pH-depend process might increase the opportunities for the SARS viruses to easily infect cells and therefore to contribute to its high infectivity. This might limit the use of chloroquine as an efficient drug against COVID-19 since its first action is to increase the cell pH. At least a neutral pH solution will not prevent the binding of the RBD to ACE2. On the opposite as it can favor this affinity.