Can Non-steroidal Anti-inflammatory Drugs Affect the Interaction Between Receptor Binding Domain of SARS-COV-2 Spike and the Human ACE2 Receptor? A Computational Biophysical Study
SARS-CoV-2 has caused millions of infections and more than 600,000 deaths worldwide. Despite the large number of studies to date, there is no specifically effective treatment available for SARS-CoV-2. However, it has been proposed to target reused drugs with potential antiviral activity to the inter...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-11-01
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| Series: | Frontiers in Physics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphy.2020.587606/full |
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| author | Lenin A. González-Paz Carla A. Lossada Francelys V. Fernández-Materán J. L. Paz Joan Vera-Villalobos Ysaias J. Alvarado |
| author_facet | Lenin A. González-Paz Carla A. Lossada Francelys V. Fernández-Materán J. L. Paz Joan Vera-Villalobos Ysaias J. Alvarado |
| author_sort | Lenin A. González-Paz |
| collection | DOAJ |
| description | SARS-CoV-2 has caused millions of infections and more than 600,000 deaths worldwide. Despite the large number of studies to date, there is no specifically effective treatment available for SARS-CoV-2. However, it has been proposed to target reused drugs with potential antiviral activity to the interface between the angiotensin-converting enzymes 2 (ACE2) and the receptor binding domain (RBD) of SARS-CoV-2 to avoid cell recognition. Some non-steroidal anti-inflammatory drugs (NSAIDs) have been reported to have some type of activity against a wide variety of viruses including SARS-CoV-2. Therefore, we carried out an exhaustive computational biophysical study of various NSAIDs targeting the RBD-ACE2 complex using multiple comparative analysis of docking and molecular dynamics. Only the Ibuprofen (Propionic acid derivative), Aspirin (Salicylate), and the Acetaminophen (p-aminophenol derivative) had a thermodynamically favorable docking with the interface of the RBD-ACE2 complex under the conditions of this study. Although, Ibuprofen was the NSAIDs with the most thermodynamically favorable docking in the shortest simulation time, and was the major inducer of structural changes, conformational changes, and overall changes in the complex throughout the simulation, including disturbances in composition and distribution of cavities at the interface. Results that point to Ibuprofen as an NSAID that, under the conditions outlined in this investigation, may have the highest probability of generating a disturbance in the stability of the RBD-ACE2 complex. This statement, although it could contribute information for the empirical treatment and prevention of COVID-19, represents only a theoretical orientation and approach, and requires its experimental demonstration because our predictions cannot secure a pharmacologically and clinically relevant interaction. However, these results are relevant due that suggest a possible mechanism of action of Ibuprofen against COVID-19 in addition to its anti-inflammatory properties, of which there are no reports in the literature. |
| first_indexed | 2024-12-12T10:00:59Z |
| format | Article |
| id | doaj.art-0f79827f5a29475b990de781b093c889 |
| institution | Directory Open Access Journal |
| issn | 2296-424X |
| language | English |
| last_indexed | 2024-12-12T10:00:59Z |
| publishDate | 2020-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physics |
| spelling | doaj.art-0f79827f5a29475b990de781b093c8892022-12-22T00:27:59ZengFrontiers Media S.A.Frontiers in Physics2296-424X2020-11-01810.3389/fphy.2020.587606587606Can Non-steroidal Anti-inflammatory Drugs Affect the Interaction Between Receptor Binding Domain of SARS-COV-2 Spike and the Human ACE2 Receptor? A Computational Biophysical StudyLenin A. González-Paz0Carla A. Lossada1Francelys V. Fernández-Materán2J. L. Paz3Joan Vera-Villalobos4Ysaias J. Alvarado5Laboratorio de Genética y Biología Molecular (L.G.B.M), Facultad Experimental de Ciencias (F.E.C), Departamento de Biología, Universidad Del Zulia (L.U.Z), Maracaibo, VenezuelaLaboratorio de Caracterización Molecular y Biomolecular, Centro de Investigación y Tecnología de Materiales (CITeMA), Instituto Venezolano de Investigaciones Científicas (IVIC), Maracaibo, VenezuelaLaboratorio de Caracterización Molecular y Biomolecular, Centro de Investigación y Tecnología de Materiales (CITeMA), Instituto Venezolano de Investigaciones Científicas (IVIC), Maracaibo, VenezuelaDepartamento de Física, Escuela Politécnica Nacional, Quito, EcuadorFacultad de Ciencias Naturales y Matemáticas, Departamento de Química y Ciencias Ambientales, Laboratorio de Análisis Químico Instrumental (LAQUINS), Escuela Superior Politécnica Del Litoral, Guayaquil, EcuadorLaboratorio de Caracterización Molecular y Biomolecular, Centro de Investigación y Tecnología de Materiales (CITeMA), Instituto Venezolano de Investigaciones Científicas (IVIC), Maracaibo, VenezuelaSARS-CoV-2 has caused millions of infections and more than 600,000 deaths worldwide. Despite the large number of studies to date, there is no specifically effective treatment available for SARS-CoV-2. However, it has been proposed to target reused drugs with potential antiviral activity to the interface between the angiotensin-converting enzymes 2 (ACE2) and the receptor binding domain (RBD) of SARS-CoV-2 to avoid cell recognition. Some non-steroidal anti-inflammatory drugs (NSAIDs) have been reported to have some type of activity against a wide variety of viruses including SARS-CoV-2. Therefore, we carried out an exhaustive computational biophysical study of various NSAIDs targeting the RBD-ACE2 complex using multiple comparative analysis of docking and molecular dynamics. Only the Ibuprofen (Propionic acid derivative), Aspirin (Salicylate), and the Acetaminophen (p-aminophenol derivative) had a thermodynamically favorable docking with the interface of the RBD-ACE2 complex under the conditions of this study. Although, Ibuprofen was the NSAIDs with the most thermodynamically favorable docking in the shortest simulation time, and was the major inducer of structural changes, conformational changes, and overall changes in the complex throughout the simulation, including disturbances in composition and distribution of cavities at the interface. Results that point to Ibuprofen as an NSAID that, under the conditions outlined in this investigation, may have the highest probability of generating a disturbance in the stability of the RBD-ACE2 complex. This statement, although it could contribute information for the empirical treatment and prevention of COVID-19, represents only a theoretical orientation and approach, and requires its experimental demonstration because our predictions cannot secure a pharmacologically and clinically relevant interaction. However, these results are relevant due that suggest a possible mechanism of action of Ibuprofen against COVID-19 in addition to its anti-inflammatory properties, of which there are no reports in the literature.https://www.frontiersin.org/articles/10.3389/fphy.2020.587606/fullSARS-COV-2NSAIDsmolecular dockingmolecular dynamicsCOVID-19 |
| spellingShingle | Lenin A. González-Paz Carla A. Lossada Francelys V. Fernández-Materán J. L. Paz Joan Vera-Villalobos Ysaias J. Alvarado Can Non-steroidal Anti-inflammatory Drugs Affect the Interaction Between Receptor Binding Domain of SARS-COV-2 Spike and the Human ACE2 Receptor? A Computational Biophysical Study Frontiers in Physics SARS-COV-2 NSAIDs molecular docking molecular dynamics COVID-19 |
| title | Can Non-steroidal Anti-inflammatory Drugs Affect the Interaction Between Receptor Binding Domain of SARS-COV-2 Spike and the Human ACE2 Receptor? A Computational Biophysical Study |
| title_full | Can Non-steroidal Anti-inflammatory Drugs Affect the Interaction Between Receptor Binding Domain of SARS-COV-2 Spike and the Human ACE2 Receptor? A Computational Biophysical Study |
| title_fullStr | Can Non-steroidal Anti-inflammatory Drugs Affect the Interaction Between Receptor Binding Domain of SARS-COV-2 Spike and the Human ACE2 Receptor? A Computational Biophysical Study |
| title_full_unstemmed | Can Non-steroidal Anti-inflammatory Drugs Affect the Interaction Between Receptor Binding Domain of SARS-COV-2 Spike and the Human ACE2 Receptor? A Computational Biophysical Study |
| title_short | Can Non-steroidal Anti-inflammatory Drugs Affect the Interaction Between Receptor Binding Domain of SARS-COV-2 Spike and the Human ACE2 Receptor? A Computational Biophysical Study |
| title_sort | can non steroidal anti inflammatory drugs affect the interaction between receptor binding domain of sars cov 2 spike and the human ace2 receptor a computational biophysical study |
| topic | SARS-COV-2 NSAIDs molecular docking molecular dynamics COVID-19 |
| url | https://www.frontiersin.org/articles/10.3389/fphy.2020.587606/full |
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