Covid-19: estudo de docking molecular com fármacos
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Tipo de documento: | Trabalho de conclusão de curso |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFAM |
Texto Completo: | http://riu.ufam.edu.br/handle/prefix/6819 |
Resumo: | Since the beginning of the Covid-19 pandemic, research groups have used in silico studies to screen potentially inhibitors for SARS-CoV-2 virus, where spike protein is the main target examines. Among these is the molecular docking, relevant in the virtual screening of structurally specific drugs, because it mimics the behavior of small molecules. Due to the urgency to find effective and safe therapies for Covid-19, strategies such as drug repositioning were widely used. With mutations leading to new variants, some selected drugs showed less affinity for their targets. The objective of this work was to perform blind docking between the drugs rendesivir, baricitinib, molnupiravir and dexamethasone with the protein Spike of the gamma, delta and omicron (BA.1) variants to obtain the best conformation of the ligands, the affinity values, as well as examine the intermolecular interactions of the complex. For this purpose, the three-dimensional structures of the drugs were optimized and the protein structures were prepared. The molecular docking proved to be adequate, with RMSD value equal to 1.2061 Å. The complexes with lower Gibbs free energies were: remdesivir - S omicron (-7.5 kcal/mol), baricitinib - S omicron (-7.0 kcal/mol), molnupiravir - S gamma (-6.6 kcal/mol) and dexamethasone - S gamma (-7.9 kcal/mol). All ligands anchored in the N-terminal region of the protein. The formation of complexes was spontaneous, and the rendesivir and baricitinib had higher affinity for the protein S variant omiron (BA.1), while the molnupiravir and dexamethasone had higher affinity for the protein S variant gamma. The most recurrent intermolecular interactions were hydrogen bonds as well as hydrophobic interactions, being relevant to the molecular recognition process of the drugs. For more conclusive studies one can approach molecular dynamics strategies. |
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Covid-19: estudo de docking molecular com fármacosSARS-CoV-2DockingFármacosVariantesCIÊNCIAS EXATAS E DA TERRA: QUÍMICADocking molecularPAXLOVIDSequenciamento genéticoVírus - GenéticaSince the beginning of the Covid-19 pandemic, research groups have used in silico studies to screen potentially inhibitors for SARS-CoV-2 virus, where spike protein is the main target examines. Among these is the molecular docking, relevant in the virtual screening of structurally specific drugs, because it mimics the behavior of small molecules. Due to the urgency to find effective and safe therapies for Covid-19, strategies such as drug repositioning were widely used. With mutations leading to new variants, some selected drugs showed less affinity for their targets. The objective of this work was to perform blind docking between the drugs rendesivir, baricitinib, molnupiravir and dexamethasone with the protein Spike of the gamma, delta and omicron (BA.1) variants to obtain the best conformation of the ligands, the affinity values, as well as examine the intermolecular interactions of the complex. For this purpose, the three-dimensional structures of the drugs were optimized and the protein structures were prepared. The molecular docking proved to be adequate, with RMSD value equal to 1.2061 Å. The complexes with lower Gibbs free energies were: remdesivir - S omicron (-7.5 kcal/mol), baricitinib - S omicron (-7.0 kcal/mol), molnupiravir - S gamma (-6.6 kcal/mol) and dexamethasone - S gamma (-7.9 kcal/mol). All ligands anchored in the N-terminal region of the protein. The formation of complexes was spontaneous, and the rendesivir and baricitinib had higher affinity for the protein S variant omiron (BA.1), while the molnupiravir and dexamethasone had higher affinity for the protein S variant gamma. The most recurrent intermolecular interactions were hydrogen bonds as well as hydrophobic interactions, being relevant to the molecular recognition process of the drugs. For more conclusive studies one can approach molecular dynamics strategies.Desde o início da pandemia de Covid-19 grupos de pesquisa utilizaram estudos in silico para selecionar potenciais inibidores do vírus SARS-CoV-2, sendo a proteína spike o principal alvo examinado. Dentre esses estudos encontra-se o docking molecular, relevante na triagem virtual de fármacos estruturalmente específicos, pois mimetiza o comportamento de pequenas moléculas. Devido a urgência em encontrar terapias eficazes e seguras para a Covid-19, estratégias como reposicionamento de fármacos foram amplamente utilizadas. Com as mutações que levaram a novas variantes, alguns fármacos selecionados demonstraram menor afinidade pelos seus alvos. O objetivo deste trabalho foi realizar o blind docking entre os fármacos rendesivir, baricitinibe, molnupiravir e dexametasona com a proteína spike das variantes gamma, delta e ômicron (BA.1) para obter a melhor conformação dos ligantes, os valores de afinidade, bem como examinar as interações intermoleculares do complexo. Para tanto otimizou-se as estruturas tridimensionais dos fármacos e preparou-se as estruturas das proteínas e dos fármacos. O docking molecular mostrou ser adequado, com valor de RMSD igual a 1,2061 Å. Os complexos com menores energias livre de Gibbs foram: rendesivir - S ômicron (-7,5 kcal/mol), baricitinibe - S ômicron (-7,0 kcal/mol), molnupiravir - S gamma (-6,6 kcal/mol) e dexametasona - S gamma (-7,9 kcal/mol). Todos os ligantes ancoraram na região N-terminal da proteína. A formação dos complexos foram espontâneas, sendo que o rendesivir e baricitinibe tiveram maior afinidade pela proteína S variante ômicron (BA.1), ao passo que o molnupiravir e dexametasona tiveram maior afinidade pela proteína S variante gamma. As interações intermoleculares mais recorrentes foram as ligações de hidrogênio bem como interações hidrofóbicas, sendo relevantes para o processo de reconhecimento molecular dos fármacos. Para estudos mais conclusivos pode-se abordar estratégias de dinâmica molecular.1NãoBrasilICE - Instituto de Ciências ExatasManaus (AM)Química - Bacharelado - ManausOliveira, Kelson Mota Teixeira dehttp://lattes.cnpq.br/8167226394049801Machado, Marcos Batistahttp://lattes.cnpq.br/9211305601802884Costa, Renyer Alveshttp://lattes.cnpq.br/8238411816105938https://orcid.org/0000-0002-8578-6967https://orcid.org/0000-0002-8791-4803https://orcid.org/0000-0002-9699-0891Lemos, Luana Caetano2023-07-18T18:49:05Z2023-07-18T18:49:05Z2023-03-03info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/bachelorThesisLEMOS, Luana Caetano. Covid-19: estudo de docking molecular com fármacos. 2023. 59 f. Trabalho de Conclusão de Curso (Bacharelado em Química) - Universidade Federal do Amazonas, Manaus, 2023.http://riu.ufam.edu.br/handle/prefix/6819porinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFAMinstname:Universidade Federal do Amazonas (UFAM)instacron:UFAM2023-07-18T18:49:58Zoai:localhost:prefix/6819Repositório InstitucionalPUBhttp://riu.ufam.edu.br/oai/requestopendoar:2023-07-18T18:49:58Repositório Institucional da UFAM - Universidade Federal do Amazonas (UFAM)false |
dc.title.none.fl_str_mv |
Covid-19: estudo de docking molecular com fármacos |
title |
Covid-19: estudo de docking molecular com fármacos |
spellingShingle |
Covid-19: estudo de docking molecular com fármacos Lemos, Luana Caetano SARS-CoV-2 Docking Fármacos Variantes CIÊNCIAS EXATAS E DA TERRA: QUÍMICA Docking molecular PAXLOVID Sequenciamento genético Vírus - Genética |
title_short |
Covid-19: estudo de docking molecular com fármacos |
title_full |
Covid-19: estudo de docking molecular com fármacos |
title_fullStr |
Covid-19: estudo de docking molecular com fármacos |
title_full_unstemmed |
Covid-19: estudo de docking molecular com fármacos |
title_sort |
Covid-19: estudo de docking molecular com fármacos |
author |
Lemos, Luana Caetano |
author_facet |
Lemos, Luana Caetano |
author_role |
author |
dc.contributor.none.fl_str_mv |
Oliveira, Kelson Mota Teixeira de http://lattes.cnpq.br/8167226394049801 Machado, Marcos Batista http://lattes.cnpq.br/9211305601802884 Costa, Renyer Alves http://lattes.cnpq.br/8238411816105938 https://orcid.org/0000-0002-8578-6967 https://orcid.org/0000-0002-8791-4803 https://orcid.org/0000-0002-9699-0891 |
dc.contributor.author.fl_str_mv |
Lemos, Luana Caetano |
dc.subject.por.fl_str_mv |
SARS-CoV-2 Docking Fármacos Variantes CIÊNCIAS EXATAS E DA TERRA: QUÍMICA Docking molecular PAXLOVID Sequenciamento genético Vírus - Genética |
topic |
SARS-CoV-2 Docking Fármacos Variantes CIÊNCIAS EXATAS E DA TERRA: QUÍMICA Docking molecular PAXLOVID Sequenciamento genético Vírus - Genética |
description |
Since the beginning of the Covid-19 pandemic, research groups have used in silico studies to screen potentially inhibitors for SARS-CoV-2 virus, where spike protein is the main target examines. Among these is the molecular docking, relevant in the virtual screening of structurally specific drugs, because it mimics the behavior of small molecules. Due to the urgency to find effective and safe therapies for Covid-19, strategies such as drug repositioning were widely used. With mutations leading to new variants, some selected drugs showed less affinity for their targets. The objective of this work was to perform blind docking between the drugs rendesivir, baricitinib, molnupiravir and dexamethasone with the protein Spike of the gamma, delta and omicron (BA.1) variants to obtain the best conformation of the ligands, the affinity values, as well as examine the intermolecular interactions of the complex. For this purpose, the three-dimensional structures of the drugs were optimized and the protein structures were prepared. The molecular docking proved to be adequate, with RMSD value equal to 1.2061 Å. The complexes with lower Gibbs free energies were: remdesivir - S omicron (-7.5 kcal/mol), baricitinib - S omicron (-7.0 kcal/mol), molnupiravir - S gamma (-6.6 kcal/mol) and dexamethasone - S gamma (-7.9 kcal/mol). All ligands anchored in the N-terminal region of the protein. The formation of complexes was spontaneous, and the rendesivir and baricitinib had higher affinity for the protein S variant omiron (BA.1), while the molnupiravir and dexamethasone had higher affinity for the protein S variant gamma. The most recurrent intermolecular interactions were hydrogen bonds as well as hydrophobic interactions, being relevant to the molecular recognition process of the drugs. For more conclusive studies one can approach molecular dynamics strategies. |
publishDate |
2023 |
dc.date.none.fl_str_mv |
2023-07-18T18:49:05Z 2023-07-18T18:49:05Z 2023-03-03 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/bachelorThesis |
format |
bachelorThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
LEMOS, Luana Caetano. Covid-19: estudo de docking molecular com fármacos. 2023. 59 f. Trabalho de Conclusão de Curso (Bacharelado em Química) - Universidade Federal do Amazonas, Manaus, 2023. http://riu.ufam.edu.br/handle/prefix/6819 |
identifier_str_mv |
LEMOS, Luana Caetano. Covid-19: estudo de docking molecular com fármacos. 2023. 59 f. Trabalho de Conclusão de Curso (Bacharelado em Química) - Universidade Federal do Amazonas, Manaus, 2023. |
url |
http://riu.ufam.edu.br/handle/prefix/6819 |
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por |
language |
por |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
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openAccess |
dc.publisher.none.fl_str_mv |
Brasil ICE - Instituto de Ciências Exatas Manaus (AM) Química - Bacharelado - Manaus |
publisher.none.fl_str_mv |
Brasil ICE - Instituto de Ciências Exatas Manaus (AM) Química - Bacharelado - Manaus |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UFAM instname:Universidade Federal do Amazonas (UFAM) instacron:UFAM |
instname_str |
Universidade Federal do Amazonas (UFAM) |
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UFAM |
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UFAM |
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Repositório Institucional da UFAM |
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Repositório Institucional da UFAM |
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Repositório Institucional da UFAM - Universidade Federal do Amazonas (UFAM) |
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