Cargando…

Improvement of native structure-based peptides as efficient inhibitors of protein-protein interactions of SARS-CoV-2 spike protein and human ACE2

New pathogens responsible for novel human disease outbreaks in the last two decades are mainly the respiratory system viruses. Not different was the last pandemic episode, caused by infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). One of the extensively explored targets,...

Descripción completa

Detalles Bibliográficos
Autores principales: Odolczyk, Norbert, Klim, Joanna, Podsiadła-Białoskórska, Małgorzata, Winiewska-Szajewska, Maria, Szolajska, Ewa, Zielenkiewicz, Urszula, Poznański, Jarosław, Zielenkiewicz, Piotr
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9555309/
https://www.ncbi.nlm.nih.gov/pubmed/36250011
http://dx.doi.org/10.3389/fmolb.2022.983014
_version_ 1784806875326316544
author Odolczyk, Norbert
Klim, Joanna
Podsiadła-Białoskórska, Małgorzata
Winiewska-Szajewska, Maria
Szolajska, Ewa
Zielenkiewicz, Urszula
Poznański, Jarosław
Zielenkiewicz, Piotr
author_facet Odolczyk, Norbert
Klim, Joanna
Podsiadła-Białoskórska, Małgorzata
Winiewska-Szajewska, Maria
Szolajska, Ewa
Zielenkiewicz, Urszula
Poznański, Jarosław
Zielenkiewicz, Piotr
author_sort Odolczyk, Norbert
collection PubMed
description New pathogens responsible for novel human disease outbreaks in the last two decades are mainly the respiratory system viruses. Not different was the last pandemic episode, caused by infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). One of the extensively explored targets, in the recent scientific literature, as a possible way for rapid development of COVID-19 specific drug(s) is the interaction between the receptor-binding domain of the virus’ spike (S) glycoprotein and human receptor angiotensin-converting enzyme 2 (hACE2). This protein-protein recognition process is involved in the early stages of the SARS-CoV-2 life cycle leading to the host cell membrane penetration. Thus, disrupting this interaction may block or significantly reduce the infection caused by the novel pathogen. Previously we have designed (by in silico structure-based analysis) three very short peptides having sequences inspirited by hACE2 native fragments, which effectively bind to the SARS-CoV-2 S protein and block its interaction with the human receptor. In continuation of the above mentioned studies, here we presented an application of molecular modeling approach resulting in improved binding affinity of the previously proposed ligand and its enhanced ability to inhibit meaningful host-virus protein-protein interaction. The new optimized hexapeptide binds to the virus protein with affinity one magnitude higher than the initial ligand and, as a very short peptide, has also great potential for further drug development. The peptide-based strategy is rapid and cost-effective for developing and optimizing efficient protein-protein interactions disruptors and may be successfully applied to discover antiviral candidates against other future emerging human viral infections.
format Online
Article
Text
id pubmed-9555309
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-95553092022-10-13 Improvement of native structure-based peptides as efficient inhibitors of protein-protein interactions of SARS-CoV-2 spike protein and human ACE2 Odolczyk, Norbert Klim, Joanna Podsiadła-Białoskórska, Małgorzata Winiewska-Szajewska, Maria Szolajska, Ewa Zielenkiewicz, Urszula Poznański, Jarosław Zielenkiewicz, Piotr Front Mol Biosci Molecular Biosciences New pathogens responsible for novel human disease outbreaks in the last two decades are mainly the respiratory system viruses. Not different was the last pandemic episode, caused by infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). One of the extensively explored targets, in the recent scientific literature, as a possible way for rapid development of COVID-19 specific drug(s) is the interaction between the receptor-binding domain of the virus’ spike (S) glycoprotein and human receptor angiotensin-converting enzyme 2 (hACE2). This protein-protein recognition process is involved in the early stages of the SARS-CoV-2 life cycle leading to the host cell membrane penetration. Thus, disrupting this interaction may block or significantly reduce the infection caused by the novel pathogen. Previously we have designed (by in silico structure-based analysis) three very short peptides having sequences inspirited by hACE2 native fragments, which effectively bind to the SARS-CoV-2 S protein and block its interaction with the human receptor. In continuation of the above mentioned studies, here we presented an application of molecular modeling approach resulting in improved binding affinity of the previously proposed ligand and its enhanced ability to inhibit meaningful host-virus protein-protein interaction. The new optimized hexapeptide binds to the virus protein with affinity one magnitude higher than the initial ligand and, as a very short peptide, has also great potential for further drug development. The peptide-based strategy is rapid and cost-effective for developing and optimizing efficient protein-protein interactions disruptors and may be successfully applied to discover antiviral candidates against other future emerging human viral infections. Frontiers Media S.A. 2022-09-28 /pmc/articles/PMC9555309/ /pubmed/36250011 http://dx.doi.org/10.3389/fmolb.2022.983014 Text en Copyright © 2022 Odolczyk, Klim, Podsiadła-Białoskórska, Winiewska-Szajewska, Szolajska, Zielenkiewicz, Poznański and Zielenkiewicz. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Odolczyk, Norbert
Klim, Joanna
Podsiadła-Białoskórska, Małgorzata
Winiewska-Szajewska, Maria
Szolajska, Ewa
Zielenkiewicz, Urszula
Poznański, Jarosław
Zielenkiewicz, Piotr
Improvement of native structure-based peptides as efficient inhibitors of protein-protein interactions of SARS-CoV-2 spike protein and human ACE2
title Improvement of native structure-based peptides as efficient inhibitors of protein-protein interactions of SARS-CoV-2 spike protein and human ACE2
title_full Improvement of native structure-based peptides as efficient inhibitors of protein-protein interactions of SARS-CoV-2 spike protein and human ACE2
title_fullStr Improvement of native structure-based peptides as efficient inhibitors of protein-protein interactions of SARS-CoV-2 spike protein and human ACE2
title_full_unstemmed Improvement of native structure-based peptides as efficient inhibitors of protein-protein interactions of SARS-CoV-2 spike protein and human ACE2
title_short Improvement of native structure-based peptides as efficient inhibitors of protein-protein interactions of SARS-CoV-2 spike protein and human ACE2
title_sort improvement of native structure-based peptides as efficient inhibitors of protein-protein interactions of sars-cov-2 spike protein and human ace2
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9555309/
https://www.ncbi.nlm.nih.gov/pubmed/36250011
http://dx.doi.org/10.3389/fmolb.2022.983014
work_keys_str_mv AT odolczyknorbert improvementofnativestructurebasedpeptidesasefficientinhibitorsofproteinproteininteractionsofsarscov2spikeproteinandhumanace2
AT klimjoanna improvementofnativestructurebasedpeptidesasefficientinhibitorsofproteinproteininteractionsofsarscov2spikeproteinandhumanace2
AT podsiadłabiałoskorskamałgorzata improvementofnativestructurebasedpeptidesasefficientinhibitorsofproteinproteininteractionsofsarscov2spikeproteinandhumanace2
AT winiewskaszajewskamaria improvementofnativestructurebasedpeptidesasefficientinhibitorsofproteinproteininteractionsofsarscov2spikeproteinandhumanace2
AT szolajskaewa improvementofnativestructurebasedpeptidesasefficientinhibitorsofproteinproteininteractionsofsarscov2spikeproteinandhumanace2
AT zielenkiewiczurszula improvementofnativestructurebasedpeptidesasefficientinhibitorsofproteinproteininteractionsofsarscov2spikeproteinandhumanace2
AT poznanskijarosław improvementofnativestructurebasedpeptidesasefficientinhibitorsofproteinproteininteractionsofsarscov2spikeproteinandhumanace2
AT zielenkiewiczpiotr improvementofnativestructurebasedpeptidesasefficientinhibitorsofproteinproteininteractionsofsarscov2spikeproteinandhumanace2