Native Structure-Based Peptides as Potential Protein–Protein Interaction Inhibitors of SARS-CoV-2 Spike Protein and Human ACE2 Receptor
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 case...
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| Format: | Article |
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MDPI AG
2021-04-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/8/2157 |
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| author | Norbert Odolczyk Ewa Marzec Maria Winiewska-Szajewska Jarosław Poznański Piotr Zielenkiewicz |
| author_facet | Norbert Odolczyk Ewa Marzec Maria Winiewska-Szajewska Jarosław Poznański Piotr Zielenkiewicz |
| author_sort | Norbert Odolczyk |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T12:28:39Z |
| format | Article |
| id | doaj.art-15092c7a0b244b96a7e2c6ba758acb57 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T12:28:39Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-15092c7a0b244b96a7e2c6ba758acb572023-11-21T14:47:51ZengMDPI AGMolecules1420-30492021-04-01268215710.3390/molecules26082157Native Structure-Based Peptides as Potential Protein–Protein Interaction Inhibitors of SARS-CoV-2 Spike Protein and Human ACE2 ReceptorNorbert Odolczyk0Ewa Marzec1Maria Winiewska-Szajewska2Jarosław Poznański3Piotr Zielenkiewicz4Laboratory of Systems Biology, Institute of Experimental Plant Biology and Biotechnology, Faculty of Biology, University of Warsaw, Miecznikowa 1, 02-096 Warsaw, PolandInstitute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a, 02-106 Warsaw, PolandInstitute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a, 02-106 Warsaw, PolandInstitute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a, 02-106 Warsaw, PolandLaboratory of Systems Biology, Institute of Experimental Plant Biology and Biotechnology, Faculty of Biology, University of Warsaw, Miecznikowa 1, 02-096 Warsaw, PolandSevere 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.https://www.mdpi.com/1420-3049/26/8/2157SARS-CoV-2COVID-19inhibitors of protein–protein interactionspeptidesdrug designcoronavirus |
| spellingShingle | Norbert Odolczyk Ewa Marzec Maria Winiewska-Szajewska Jarosław Poznański Piotr Zielenkiewicz Native Structure-Based Peptides as Potential Protein–Protein Interaction Inhibitors of SARS-CoV-2 Spike Protein and Human ACE2 Receptor Molecules SARS-CoV-2 COVID-19 inhibitors of protein–protein interactions peptides drug design coronavirus |
| title | Native Structure-Based Peptides as Potential Protein–Protein Interaction Inhibitors of SARS-CoV-2 Spike Protein and Human ACE2 Receptor |
| title_full | Native Structure-Based Peptides as Potential Protein–Protein Interaction Inhibitors of SARS-CoV-2 Spike Protein and Human ACE2 Receptor |
| title_fullStr | Native Structure-Based Peptides as Potential Protein–Protein Interaction Inhibitors of SARS-CoV-2 Spike Protein and Human ACE2 Receptor |
| title_full_unstemmed | Native Structure-Based Peptides as Potential Protein–Protein Interaction Inhibitors of SARS-CoV-2 Spike Protein and Human ACE2 Receptor |
| title_short | Native Structure-Based Peptides as Potential Protein–Protein Interaction Inhibitors of SARS-CoV-2 Spike Protein and Human ACE2 Receptor |
| title_sort | native structure based peptides as potential protein protein interaction inhibitors of sars cov 2 spike protein and human ace2 receptor |
| topic | SARS-CoV-2 COVID-19 inhibitors of protein–protein interactions peptides drug design coronavirus |
| url | https://www.mdpi.com/1420-3049/26/8/2157 |
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