tetano
Editor, Senior Moderator
Biophys J
. 2020 Aug 27;S0006-3495(20)30670-6.
doi: 10.1016/j.bpj.2020.08.022. Online ahead of print.
The Inhibitory Effect of a Coronavirus Spike Protein Fragment with ACE2
Emanuel K Peter[SUP] 1 [/SUP], Alexander Schug[SUP] 2 [/SUP]
Affiliations
Abstract
In this article, we investigate the binding processes of a fragment of the coronavirus spike protein receptor binding domain (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 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 simulation. We then evaluate the effect of the hexapeptide on the assembly process of the CoV-2 RBD to ACE2 in long-time enhanced correlation guided 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 because of 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 that prevents the viral activation through the inhibition of the interaction between ACE2 and CoV-2 RBD.
. 2020 Aug 27;S0006-3495(20)30670-6.
doi: 10.1016/j.bpj.2020.08.022. Online ahead of print.
The Inhibitory Effect of a Coronavirus Spike Protein Fragment with ACE2
Emanuel K Peter[SUP] 1 [/SUP], Alexander Schug[SUP] 2 [/SUP]
Affiliations
- PMID: 32941783
- DOI: 10.1016/j.bpj.2020.08.022
Abstract
In this article, we investigate the binding processes of a fragment of the coronavirus spike protein receptor binding domain (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 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 simulation. We then evaluate the effect of the hexapeptide on the assembly process of the CoV-2 RBD to ACE2 in long-time enhanced correlation guided 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 because of 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 that prevents the viral activation through the inhibition of the interaction between ACE2 and CoV-2 RBD.