Journal Article

FZJ-2020-04934

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The Inhibitory Effect of a Coronavirus Spike Protein Fragment with ACE2

Peter, E. K.FZJ* ; Schug, A. (Corresponding author)FZJ*

2021
Soc. Bethesda, Md.

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Please use a persistent id in citations: http://hdl.handle.net/2128/27492  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.

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Contributing Institute(s):

1. Jülich Supercomputing Center (JSC)
2. John von Neumann - Institut für Computing (NIC)

Research Program(s):

1. 5111 - Domain-Specific Simulation & Data Life Cycle Labs (SDLs) and Research Groups (POF4-511) (POF4-511)
2. Forschergruppe Schug (hkf6_20200501) (hkf6_20200501)

Appears in the scientific report 2021

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Database coverage:
; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Essential Science Indicators ; IF < 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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