The inhibitory effect of a Corona virus spike protein fragment with ACE2

Peter, Emanuel K.; Schug, Alexander

In this paper, we investigate the binding processes of a fragment of the Coronavirus spike protein receptor binding domain (CoV RBD), the hexapeptide YKYRYL on the angiotensin converting enzyme 2 (ACE2) receptor and its inhibitory effect on the binding and activation of the Coronavirus-2 spike protein receptor binding domain CoV-2 RBD at ACE2. In agreement with an experimental study, we find a high affinity of the hexapeptide to the binding interface between CoV-2 RBD and ACE2, which we investigate using 20 independent equilibrium Molecular Dynamics (MD) simulations over a total of 1 μs and a 200 ns enhanced correlation guided MD (CORE-MD) simulation. We then evaluate the effect of the hexapeptide on the assembly process of the CoV-2 RBD to ACE2 in long-time enhanced CORE-MD simulations. In that set of simulations, we find that CoV-2 RBD does not bind to ACE2 with the binding motif shown in experiments, but it rotates due to an electrostatic repulsion and forms a hydrophobic interface with ACE2. Surprisingly, we observe that the hexapeptide binds to CoV-2 RBD, which has the effect that this protein only weakly attaches to ACE2, so that the activation of CoV-2 RBD might be inhibited in this case. Our results indicate that the hexapeptide might be a possible treatment option which prevents the viral activation through the inhibition of the interaction between ACE2 and CoV-2 RBD.