Binding behavior of receptor binding domain of the SARS-CoV-2 virus and ivermectin
Abstract The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), sparked an international debate on effective ways to prevent and treat the virus. Specifically, there were many varying opinions on the use of ivermectin (IVM) throughout the world, with minimal r...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-02-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-53086-0 |
| _version_ | 1797274557712695296 |
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| author | Kasidy R. Gossen Meiyi Zhang Zivko L. Nikolov Sandun D. Fernando Maria D. King |
| author_facet | Kasidy R. Gossen Meiyi Zhang Zivko L. Nikolov Sandun D. Fernando Maria D. King |
| author_sort | Kasidy R. Gossen |
| collection | DOAJ |
| description | Abstract The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), sparked an international debate on effective ways to prevent and treat the virus. Specifically, there were many varying opinions on the use of ivermectin (IVM) throughout the world, with minimal research to support either side. IVM is an FDA-approved antiparasitic drug that was discovered in the 1970s and was found to show antiviral activity. The objective of this study is to examine the binding behavior and rates of association and dissociation between SARS-CoV-2 receptor binding domain (RBD), IVM, and their combination using aminopropylsilane (APS) biosensors as surrogates for the hydrophobic interaction between the viral protein and human angiotensin-converting enzyme 2 (ACE2) receptors to determine the potential of IVM as a repurposed drug for SARS-CoV-2 prevention and treatment. The IVM, RBD, and combination binding kinetics were analyzed using biolayer interferometry (BLI) and validated with multiple in silico techniques including protein–ligand docking, molecular dynamics simulation, molecular mechanics-generalized Born surface area (MM-GBSA), and principal component analysis (PCA). Our results suggest that with increasing IVM concentrations the association rate with the hydrophobic biosensor increases with a simultaneous decrease in dissociation. Significant kinetic changes to RBD, when combined with IVM, were found only at a concentration a thousand times the approved dosage with minimal changes found over a 35-min time period. Our study suggests that IVM is not an effective preventative or treatment method at the currently approved dosage. |
| first_indexed | 2024-03-07T15:00:06Z |
| format | Article |
| id | doaj.art-17fc846ac8a14e0b95c3c009cce007e7 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-07T15:00:06Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-17fc846ac8a14e0b95c3c009cce007e72024-03-05T19:10:00ZengNature PortfolioScientific Reports2045-23222024-02-0114111410.1038/s41598-024-53086-0Binding behavior of receptor binding domain of the SARS-CoV-2 virus and ivermectinKasidy R. Gossen0Meiyi Zhang1Zivko L. Nikolov2Sandun D. Fernando3Maria D. King4Department of Biological and Agricultural Engineering, Texas A&M UniversityDepartment of Biological and Agricultural Engineering, Texas A&M UniversityDepartment of Biological and Agricultural Engineering, Texas A&M UniversityDepartment of Biological and Agricultural Engineering, Texas A&M UniversityDepartment of Biological and Agricultural Engineering, Texas A&M UniversityAbstract The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), sparked an international debate on effective ways to prevent and treat the virus. Specifically, there were many varying opinions on the use of ivermectin (IVM) throughout the world, with minimal research to support either side. IVM is an FDA-approved antiparasitic drug that was discovered in the 1970s and was found to show antiviral activity. The objective of this study is to examine the binding behavior and rates of association and dissociation between SARS-CoV-2 receptor binding domain (RBD), IVM, and their combination using aminopropylsilane (APS) biosensors as surrogates for the hydrophobic interaction between the viral protein and human angiotensin-converting enzyme 2 (ACE2) receptors to determine the potential of IVM as a repurposed drug for SARS-CoV-2 prevention and treatment. The IVM, RBD, and combination binding kinetics were analyzed using biolayer interferometry (BLI) and validated with multiple in silico techniques including protein–ligand docking, molecular dynamics simulation, molecular mechanics-generalized Born surface area (MM-GBSA), and principal component analysis (PCA). Our results suggest that with increasing IVM concentrations the association rate with the hydrophobic biosensor increases with a simultaneous decrease in dissociation. Significant kinetic changes to RBD, when combined with IVM, were found only at a concentration a thousand times the approved dosage with minimal changes found over a 35-min time period. Our study suggests that IVM is not an effective preventative or treatment method at the currently approved dosage.https://doi.org/10.1038/s41598-024-53086-0 |
| spellingShingle | Kasidy R. Gossen Meiyi Zhang Zivko L. Nikolov Sandun D. Fernando Maria D. King Binding behavior of receptor binding domain of the SARS-CoV-2 virus and ivermectin Scientific Reports |
| title | Binding behavior of receptor binding domain of the SARS-CoV-2 virus and ivermectin |
| title_full | Binding behavior of receptor binding domain of the SARS-CoV-2 virus and ivermectin |
| title_fullStr | Binding behavior of receptor binding domain of the SARS-CoV-2 virus and ivermectin |
| title_full_unstemmed | Binding behavior of receptor binding domain of the SARS-CoV-2 virus and ivermectin |
| title_short | Binding behavior of receptor binding domain of the SARS-CoV-2 virus and ivermectin |
| title_sort | binding behavior of receptor binding domain of the sars cov 2 virus and ivermectin |
| url | https://doi.org/10.1038/s41598-024-53086-0 |
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