Designing Short Peptides to Block the Interaction of SARS-CoV-2 and Human ACE2 for COVID-19 Therapeutics
To date, the current COVID-19 pandemic caused by SARS-CoV-2 has infected 99.2 million while killed 2.2 million people throughout the world and is still spreading widely. The unavailability of potential therapeutics against this virus urges to search and develop new drugs. SARS-CoV-2 enters human cel...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-08-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.731828/full |
| _version_ | 1818682704371122176 |
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| author | Abdul Basit Asad Mustafa Karim Muhammad Asif Tanveer Ali Jung Hun Lee Jeong Ho Jeon Shafiq ur Rehman Sang Hee Lee |
| author_facet | Abdul Basit Asad Mustafa Karim Muhammad Asif Tanveer Ali Jung Hun Lee Jeong Ho Jeon Shafiq ur Rehman Sang Hee Lee |
| author_sort | Abdul Basit |
| collection | DOAJ |
| description | To date, the current COVID-19 pandemic caused by SARS-CoV-2 has infected 99.2 million while killed 2.2 million people throughout the world and is still spreading widely. The unavailability of potential therapeutics against this virus urges to search and develop new drugs. SARS-CoV-2 enters human cells by interacting with human angiotensin-converting enzyme 2 (ACE2) receptor expressed on human cell surface through utilizing receptor-binding domain (RBD) of its spike glycoprotein. The RBD is highly conserved and is also a potential target for blocking its interaction with human cell surface receptor. We designed short peptides on the basis of our previously reported truncated ACE2 (tACE2) for increasing the binding affinity as well as the binding interaction network with RBD. These peptides can selectively bind to RBD with much higher affinities than the cell surface receptor. Thus, these can block all the binding residues required for binding to cell surface receptor. We used selected amino acid regions (21–40 and 65–75) of ACE2 as scaffold for the de novo peptide design. Our designed peptide Pep1 showed interactions with RBD covering almost all of its binding residues with significantly higher binding affinity (−13.2 kcal mol−1) than the cell surface receptor. The molecular dynamics (MD) simulation results showed that designed peptides form a stabilized complex with RBD. We suggest that blocking the RBD through de novo designed peptides can serve as a potential candidate for COVID-19 treatment after further clinical investigations. |
| first_indexed | 2024-12-17T10:23:04Z |
| format | Article |
| id | doaj.art-d6c3bf19d3b345008463acb1c0e0c3cc |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-17T10:23:04Z |
| publishDate | 2021-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-d6c3bf19d3b345008463acb1c0e0c3cc2022-12-21T21:52:44ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-08-011210.3389/fphar.2021.731828731828Designing Short Peptides to Block the Interaction of SARS-CoV-2 and Human ACE2 for COVID-19 TherapeuticsAbdul Basit0Asad Mustafa Karim1Muhammad Asif2Tanveer Ali3Jung Hun Lee4Jeong Ho Jeon5Shafiq ur Rehman6Sang Hee Lee7Institute of Microbiology and Molecular Genetics, University of the Punjab, Lahore, PakistanDepartment of Bioscience and Biotechnology, The University of Suwon, Hwaseong, South KoreaInstitute of Microbiology and Molecular Genetics, University of the Punjab, Lahore, PakistanDepartment of Host Defense, Graduate School of Medicine, University of the Ryukyus, Nishihara, JapanNational Leading Research Laboratory, Department of Biological Sciences, Myongji University, Yongin, South KoreaNational Leading Research Laboratory, Department of Biological Sciences, Myongji University, Yongin, South KoreaInstitute of Microbiology and Molecular Genetics, University of the Punjab, Lahore, PakistanNational Leading Research Laboratory, Department of Biological Sciences, Myongji University, Yongin, South KoreaTo date, the current COVID-19 pandemic caused by SARS-CoV-2 has infected 99.2 million while killed 2.2 million people throughout the world and is still spreading widely. The unavailability of potential therapeutics against this virus urges to search and develop new drugs. SARS-CoV-2 enters human cells by interacting with human angiotensin-converting enzyme 2 (ACE2) receptor expressed on human cell surface through utilizing receptor-binding domain (RBD) of its spike glycoprotein. The RBD is highly conserved and is also a potential target for blocking its interaction with human cell surface receptor. We designed short peptides on the basis of our previously reported truncated ACE2 (tACE2) for increasing the binding affinity as well as the binding interaction network with RBD. These peptides can selectively bind to RBD with much higher affinities than the cell surface receptor. Thus, these can block all the binding residues required for binding to cell surface receptor. We used selected amino acid regions (21–40 and 65–75) of ACE2 as scaffold for the de novo peptide design. Our designed peptide Pep1 showed interactions with RBD covering almost all of its binding residues with significantly higher binding affinity (−13.2 kcal mol−1) than the cell surface receptor. The molecular dynamics (MD) simulation results showed that designed peptides form a stabilized complex with RBD. We suggest that blocking the RBD through de novo designed peptides can serve as a potential candidate for COVID-19 treatment after further clinical investigations.https://www.frontiersin.org/articles/10.3389/fphar.2021.731828/fullCOVID-19SARS-CoV-2RBDdesigned peptides glycoprotein |
| spellingShingle | Abdul Basit Asad Mustafa Karim Muhammad Asif Tanveer Ali Jung Hun Lee Jeong Ho Jeon Shafiq ur Rehman Sang Hee Lee Designing Short Peptides to Block the Interaction of SARS-CoV-2 and Human ACE2 for COVID-19 Therapeutics Frontiers in Pharmacology COVID-19 SARS-CoV-2 RBD designed peptide s glycoprotein |
| title | Designing Short Peptides to Block the Interaction of SARS-CoV-2 and Human ACE2 for COVID-19 Therapeutics |
| title_full | Designing Short Peptides to Block the Interaction of SARS-CoV-2 and Human ACE2 for COVID-19 Therapeutics |
| title_fullStr | Designing Short Peptides to Block the Interaction of SARS-CoV-2 and Human ACE2 for COVID-19 Therapeutics |
| title_full_unstemmed | Designing Short Peptides to Block the Interaction of SARS-CoV-2 and Human ACE2 for COVID-19 Therapeutics |
| title_short | Designing Short Peptides to Block the Interaction of SARS-CoV-2 and Human ACE2 for COVID-19 Therapeutics |
| title_sort | designing short peptides to block the interaction of sars cov 2 and human ace2 for covid 19 therapeutics |
| topic | COVID-19 SARS-CoV-2 RBD designed peptide s glycoprotein |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.731828/full |
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