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Native Structure-Based Peptides as Potential Protein-Protein Interaction Inhibitors of SARS-CoV-2 Spike Protein and Human ACE2 Receptor.
Molecules. 2021 Apr 09; 26(8)M

Abstract

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is a positive-strand RNA virus that causes severe respiratory syndrome in humans, which is now referred to as coronavirus disease 2019 (COVID-19). Since December 2019, the new pathogen has rapidly spread globally, with over 65 million cases reported to the beginning of December 2020, including over 1.5 million deaths. Unfortunately, currently, there is no specific and effective treatment for COVID-19. As SARS-CoV-2 relies on its spike proteins (S) to bind to a host cell-surface receptor angiotensin-converting enzyme-2(ACE2), and this interaction is proved to be responsible for entering a virus into host cells, it makes an ideal target for antiviral drug development. In this work, we design three very short peptides based on the ACE2 sequence/structure fragments, which may effectively bind to the receptor-binding domain (RBD) of S protein and may, in turn, disrupt the important virus-host protein-protein interactions, blocking early steps of SARS-CoV-2 infection. Two of our peptides bind to virus protein with affinity in nanomolar range, and as very short peptides have great potential for drug development.

Authors+Show Affiliations

Laboratory of Systems Biology, Institute of Experimental Plant Biology and Biotechnology, Faculty of Biology, University of Warsaw, Miecznikowa 1, 02-096 Warsaw, Poland. Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a, 02-106 Warsaw, Poland.Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a, 02-106 Warsaw, Poland.Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a, 02-106 Warsaw, Poland.Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a, 02-106 Warsaw, Poland.Laboratory of Systems Biology, Institute of Experimental Plant Biology and Biotechnology, Faculty of Biology, University of Warsaw, Miecznikowa 1, 02-096 Warsaw, Poland. Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a, 02-106 Warsaw, Poland.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33918595

Citation

Odolczyk, Norbert, et al. "Native Structure-Based Peptides as Potential Protein-Protein Interaction Inhibitors of SARS-CoV-2 Spike Protein and Human ACE2 Receptor." Molecules (Basel, Switzerland), vol. 26, no. 8, 2021.
Odolczyk N, Marzec E, Winiewska-Szajewska M, et al. Native Structure-Based Peptides as Potential Protein-Protein Interaction Inhibitors of SARS-CoV-2 Spike Protein and Human ACE2 Receptor. Molecules. 2021;26(8).
Odolczyk, N., Marzec, E., Winiewska-Szajewska, M., Poznański, J., & Zielenkiewicz, P. (2021). Native Structure-Based Peptides as Potential Protein-Protein Interaction Inhibitors of SARS-CoV-2 Spike Protein and Human ACE2 Receptor. Molecules (Basel, Switzerland), 26(8). https://doi.org/10.3390/molecules26082157
Odolczyk N, et al. Native Structure-Based Peptides as Potential Protein-Protein Interaction Inhibitors of SARS-CoV-2 Spike Protein and Human ACE2 Receptor. Molecules. 2021 Apr 9;26(8) PubMed PMID: 33918595.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Native Structure-Based Peptides as Potential Protein-Protein Interaction Inhibitors of SARS-CoV-2 Spike Protein and Human ACE2 Receptor. AU - Odolczyk,Norbert, AU - Marzec,Ewa, AU - Winiewska-Szajewska,Maria, AU - Poznański,Jarosław, AU - Zielenkiewicz,Piotr, Y1 - 2021/04/09/ PY - 2021/03/08/received PY - 2021/04/07/accepted PY - 2021/4/30/entrez PY - 2021/5/1/pubmed PY - 2021/5/6/medline KW - ACE2 KW - COVID-19 KW - SARS-CoV-2 KW - angiotensin-converting enzyme-2 KW - coronavirus KW - drug design KW - inhibitors of protein–protein interactions KW - peptides JF - Molecules (Basel, Switzerland) JO - Molecules VL - 26 IS - 8 N2 - Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is a positive-strand RNA virus that causes severe respiratory syndrome in humans, which is now referred to as coronavirus disease 2019 (COVID-19). Since December 2019, the new pathogen has rapidly spread globally, with over 65 million cases reported to the beginning of December 2020, including over 1.5 million deaths. Unfortunately, currently, there is no specific and effective treatment for COVID-19. As SARS-CoV-2 relies on its spike proteins (S) to bind to a host cell-surface receptor angiotensin-converting enzyme-2(ACE2), and this interaction is proved to be responsible for entering a virus into host cells, it makes an ideal target for antiviral drug development. In this work, we design three very short peptides based on the ACE2 sequence/structure fragments, which may effectively bind to the receptor-binding domain (RBD) of S protein and may, in turn, disrupt the important virus-host protein-protein interactions, blocking early steps of SARS-CoV-2 infection. Two of our peptides bind to virus protein with affinity in nanomolar range, and as very short peptides have great potential for drug development. SN - 1420-3049 UR - https://www.unboundmedicine.com/medline/citation/33918595/Native_Structure_Based_Peptides_as_Potential_Protein_Protein_Interaction_Inhibitors_of_SARS_CoV_2_Spike_Protein_and_Human_ACE2_Receptor_ DB - PRIME DP - Unbound Medicine ER -