Lopinavir and Ritonavir have High Affinity Toward the SARS-CoV-2 S-protein Receptor-binding Domain Sequenced in Brazil
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first identified in China in December 2019, rapidly spread worldwide, resulting in the coronavirus disease 2019 (COVID-19) pandemic. Understanding the structural and functional interactions between the virus and host cells is...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Compuscript Ltd
2025-01-01
|
| Series: | BIO Integration |
| Subjects: | |
| Online Access: | https://www.scienceopen.com/hosted-document?doi=10.15212/bioi-2024-0055 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832542918953402368 |
|---|---|
| author | Aline Diogo Marinho Helyson Lucas Bezerra Braz João Alison de Moraes Silveira Danilo Galvão Rocha Roberta Jeane Bezerra Jorge Geanne Matos de Andrade |
| author_facet | Aline Diogo Marinho Helyson Lucas Bezerra Braz João Alison de Moraes Silveira Danilo Galvão Rocha Roberta Jeane Bezerra Jorge Geanne Matos de Andrade |
| author_sort | Aline Diogo Marinho |
| collection | DOAJ |
| description | Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first identified in China in December 2019, rapidly spread worldwide, resulting in the coronavirus disease 2019 (COVID-19) pandemic. Understanding the structural and functional interactions between the virus and host cells is critical for developing therapeutic strategies. Methods: In this study, we employed in silico docking models to investigate the molecular interactions between the receptor-binding domain (RBD) of the SARS-CoV-2 spike glycoprotein, derived from the Brazilian genome sequence, and seven clinically approved drugs: umifenovir, darunavir, lopinavir, ritonavir, remdesivir, pirfenidone, and oseltamivir. The three-dimensional structure of the Omicron RBD model was generated through homology modeling, and potential active site cavities were predicted within the RBD structure. Results: Among the seven drugs tested, only lopinavir and ritonavir demonstrated significant binding affinities to the RBD. Lopinavir exhibited a binding affinity of −9.8 kcal/mol, forming interactions with residues PHE168, GLY167, SER176, GLN175, GLU166, LEU134, LEU137, TYR171, PHE138, LEU174, and PHE172. Ritonavir showed a binding affinity of −8.9 kcal/mol, interacting with residues ARG148, ASN130, VAL23, SER81, ASN33, PHE29, TYR33, SER31, ASN132, ALA26, ALA30, ALA34, and TYR133.Molecular dynamics simulations confirmed the stability of the complexes formed between lopinavir and ritonavir and the RBD active site. Conclusion: These findings underscore the potential of these protease inhibitors as therapeutic agents targeting the SARS-CoV-2 spike protein. |
| format | Article |
| id | doaj-art-c46afcd01ca34899ac86dbc5326d50a7 |
| institution | Kabale University |
| issn | 2712-0082 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Compuscript Ltd |
| record_format | Article |
| series | BIO Integration |
| spelling | doaj-art-c46afcd01ca34899ac86dbc5326d50a72025-02-03T12:21:40ZengCompuscript LtdBIO Integration2712-00822025-01-016110.15212/bioi-2024-0055Lopinavir and Ritonavir have High Affinity Toward the SARS-CoV-2 S-protein Receptor-binding Domain Sequenced in BrazilAline Diogo Marinho0Helyson Lucas Bezerra Braz1João Alison de Moraes Silveira2Danilo Galvão Rocha3Roberta Jeane Bezerra Jorge4Geanne Matos de Andrade5PostGraduate Programme in Medical Sciences, Department of Medicine, School of Medicine, Federal University of Ceará, Professor Costa Mendes St., 1608, 60.430-140, Fortaleza-CE, BrazilDrug Research and Development Center, Federal University of Ceara, Coronel Nunes de Melo St., 1000, 60.430-275, Fortaleza-CE, BrazilDrug Research and Development Center, Federal University of Ceara, Coronel Nunes de Melo St., 1000, 60.430-275, Fortaleza-CE, BrazilDrug Research and Development Center, Federal University of Ceara, Coronel Nunes de Melo St., 1000, 60.430-275, Fortaleza-CE, BrazilDrug Research and Development Center, Federal University of Ceara, Coronel Nunes de Melo St., 1000, 60.430-275, Fortaleza-CE, BrazilPostGraduate Programme in Medical Sciences, Department of Medicine, School of Medicine, Federal University of Ceará, Professor Costa Mendes St., 1608, 60.430-140, Fortaleza-CE, BrazilBackground: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first identified in China in December 2019, rapidly spread worldwide, resulting in the coronavirus disease 2019 (COVID-19) pandemic. Understanding the structural and functional interactions between the virus and host cells is critical for developing therapeutic strategies. Methods: In this study, we employed in silico docking models to investigate the molecular interactions between the receptor-binding domain (RBD) of the SARS-CoV-2 spike glycoprotein, derived from the Brazilian genome sequence, and seven clinically approved drugs: umifenovir, darunavir, lopinavir, ritonavir, remdesivir, pirfenidone, and oseltamivir. The three-dimensional structure of the Omicron RBD model was generated through homology modeling, and potential active site cavities were predicted within the RBD structure. Results: Among the seven drugs tested, only lopinavir and ritonavir demonstrated significant binding affinities to the RBD. Lopinavir exhibited a binding affinity of −9.8 kcal/mol, forming interactions with residues PHE168, GLY167, SER176, GLN175, GLU166, LEU134, LEU137, TYR171, PHE138, LEU174, and PHE172. Ritonavir showed a binding affinity of −8.9 kcal/mol, interacting with residues ARG148, ASN130, VAL23, SER81, ASN33, PHE29, TYR33, SER31, ASN132, ALA26, ALA30, ALA34, and TYR133.Molecular dynamics simulations confirmed the stability of the complexes formed between lopinavir and ritonavir and the RBD active site. Conclusion: These findings underscore the potential of these protease inhibitors as therapeutic agents targeting the SARS-CoV-2 spike protein.https://www.scienceopen.com/hosted-document?doi=10.15212/bioi-2024-0055covid-19molecular dockingprotease inhibitorsreceptor-binding domainsars-cov-2spike glycoprotein |
| spellingShingle | Aline Diogo Marinho Helyson Lucas Bezerra Braz João Alison de Moraes Silveira Danilo Galvão Rocha Roberta Jeane Bezerra Jorge Geanne Matos de Andrade Lopinavir and Ritonavir have High Affinity Toward the SARS-CoV-2 S-protein Receptor-binding Domain Sequenced in Brazil BIO Integration covid-19 molecular docking protease inhibitors receptor-binding domain sars-cov-2 spike glycoprotein |
| title | Lopinavir and Ritonavir have High Affinity Toward the SARS-CoV-2 S-protein Receptor-binding Domain Sequenced in Brazil |
| title_full | Lopinavir and Ritonavir have High Affinity Toward the SARS-CoV-2 S-protein Receptor-binding Domain Sequenced in Brazil |
| title_fullStr | Lopinavir and Ritonavir have High Affinity Toward the SARS-CoV-2 S-protein Receptor-binding Domain Sequenced in Brazil |
| title_full_unstemmed | Lopinavir and Ritonavir have High Affinity Toward the SARS-CoV-2 S-protein Receptor-binding Domain Sequenced in Brazil |
| title_short | Lopinavir and Ritonavir have High Affinity Toward the SARS-CoV-2 S-protein Receptor-binding Domain Sequenced in Brazil |
| title_sort | lopinavir and ritonavir have high affinity toward the sars cov 2 s protein receptor binding domain sequenced in brazil |
| topic | covid-19 molecular docking protease inhibitors receptor-binding domain sars-cov-2 spike glycoprotein |
| url | https://www.scienceopen.com/hosted-document?doi=10.15212/bioi-2024-0055 |
| work_keys_str_mv | AT alinediogomarinho lopinavirandritonavirhavehighaffinitytowardthesarscov2sproteinreceptorbindingdomainsequencedinbrazil AT helysonlucasbezerrabraz lopinavirandritonavirhavehighaffinitytowardthesarscov2sproteinreceptorbindingdomainsequencedinbrazil AT joaoalisondemoraessilveira lopinavirandritonavirhavehighaffinitytowardthesarscov2sproteinreceptorbindingdomainsequencedinbrazil AT danilogalvaorocha lopinavirandritonavirhavehighaffinitytowardthesarscov2sproteinreceptorbindingdomainsequencedinbrazil AT robertajeanebezerrajorge lopinavirandritonavirhavehighaffinitytowardthesarscov2sproteinreceptorbindingdomainsequencedinbrazil AT geannematosdeandrade lopinavirandritonavirhavehighaffinitytowardthesarscov2sproteinreceptorbindingdomainsequencedinbrazil |