ACE2 : S1 RBD Interaction-Targeted Peptides and Small Molecules as Potential COVID-19 Therapeutics
The COVID-19 pandemic that began in late 2019 continues with new challenges arising due to antigenic drift as well as individuals who cannot or choose not to take the vaccine. There is therefore an urgent need for additional therapies that complement vaccines and approved therapies such as antibodie...
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Advances in Pharmacological and Pharmaceutical Sciences |
| Online Access: | http://dx.doi.org/10.1155/2021/1828792 |
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| author | Lennox Chitsike John Krstenansky Penelope J. Duerksen-Hughes |
| author_facet | Lennox Chitsike John Krstenansky Penelope J. Duerksen-Hughes |
| author_sort | Lennox Chitsike |
| collection | DOAJ |
| description | The COVID-19 pandemic that began in late 2019 continues with new challenges arising due to antigenic drift as well as individuals who cannot or choose not to take the vaccine. There is therefore an urgent need for additional therapies that complement vaccines and approved therapies such as antibodies in the fight to end or slow down the pandemic. SARS-CoV-2 initiates invasion of the human target cell through direct contact between the receptor-binding domain of its Spike protein and its cellular receptor, angiotensin-converting enzyme-2 (ACE2). The ACE2 and S1 RBD interaction, therefore, represents an attractive therapeutic intervention to prevent viral entry and spread. In this study, we developed a proximity-based AlphaScreen™ assay that can be utilized to quickly and efficiently screen for inhibitors that perturb the ACE2 : S1 RBD interaction. We then designed several peptides candidates from motifs in ACE2 and S1 RBD that play critical roles in the interaction, with and without modifications to the native sequences. We also assessed the possibility of reprofiling of candidate small molecules that previously have been shown to interfere with the viral entry of SARS-CoV. Using our optimized AlphaScreen™ assay, we evaluated the activity and specificity of these peptides and small molecules in inhibiting the binding of ACE2 : S1 RBD. This screen identified cepharanthine as a promising candidate for development as a SARS-CoV-2 entry inhibitor. |
| format | Article |
| id | doaj-art-d6e879b16c5548e1968b728e0cc242cb |
| institution | Kabale University |
| issn | 2633-4690 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advances in Pharmacological and Pharmaceutical Sciences |
| spelling | doaj-art-d6e879b16c5548e1968b728e0cc242cb2025-02-03T06:45:53ZengWileyAdvances in Pharmacological and Pharmaceutical Sciences2633-46902021-01-01202110.1155/2021/1828792ACE2 : S1 RBD Interaction-Targeted Peptides and Small Molecules as Potential COVID-19 TherapeuticsLennox Chitsike0John Krstenansky1Penelope J. Duerksen-Hughes2Department of Basic SciencesDepartment of Pharmaceutical and Applied Life SciencesDepartment of Basic SciencesThe COVID-19 pandemic that began in late 2019 continues with new challenges arising due to antigenic drift as well as individuals who cannot or choose not to take the vaccine. There is therefore an urgent need for additional therapies that complement vaccines and approved therapies such as antibodies in the fight to end or slow down the pandemic. SARS-CoV-2 initiates invasion of the human target cell through direct contact between the receptor-binding domain of its Spike protein and its cellular receptor, angiotensin-converting enzyme-2 (ACE2). The ACE2 and S1 RBD interaction, therefore, represents an attractive therapeutic intervention to prevent viral entry and spread. In this study, we developed a proximity-based AlphaScreen™ assay that can be utilized to quickly and efficiently screen for inhibitors that perturb the ACE2 : S1 RBD interaction. We then designed several peptides candidates from motifs in ACE2 and S1 RBD that play critical roles in the interaction, with and without modifications to the native sequences. We also assessed the possibility of reprofiling of candidate small molecules that previously have been shown to interfere with the viral entry of SARS-CoV. Using our optimized AlphaScreen™ assay, we evaluated the activity and specificity of these peptides and small molecules in inhibiting the binding of ACE2 : S1 RBD. This screen identified cepharanthine as a promising candidate for development as a SARS-CoV-2 entry inhibitor.http://dx.doi.org/10.1155/2021/1828792 |
| spellingShingle | Lennox Chitsike John Krstenansky Penelope J. Duerksen-Hughes ACE2 : S1 RBD Interaction-Targeted Peptides and Small Molecules as Potential COVID-19 Therapeutics Advances in Pharmacological and Pharmaceutical Sciences |
| title | ACE2 : S1 RBD Interaction-Targeted Peptides and Small Molecules as Potential COVID-19 Therapeutics |
| title_full | ACE2 : S1 RBD Interaction-Targeted Peptides and Small Molecules as Potential COVID-19 Therapeutics |
| title_fullStr | ACE2 : S1 RBD Interaction-Targeted Peptides and Small Molecules as Potential COVID-19 Therapeutics |
| title_full_unstemmed | ACE2 : S1 RBD Interaction-Targeted Peptides and Small Molecules as Potential COVID-19 Therapeutics |
| title_short | ACE2 : S1 RBD Interaction-Targeted Peptides and Small Molecules as Potential COVID-19 Therapeutics |
| title_sort | ace2 s1 rbd interaction targeted peptides and small molecules as potential covid 19 therapeutics |
| url | http://dx.doi.org/10.1155/2021/1828792 |
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